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Liquid biopsy provides accurate, fast Dx of HPV-associated head and neck cancer

Source: www.medpagetoday.com
Author: Mike Bassett, Staff Writer, MedPage Today

The use of liquid biopsy for the diagnosis of human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) was more accurate, faster, and less expensive than standard tissue-based biopsies, according to a prospective observational study.

The sensitivity and specificity of this circulating tumor HPV DNA-based approach were 98.4% and 98.6%, respectively, with positive and negative predictive values of 98.4% and 98.6%, reported Daniel L. Faden, MD, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues.

The diagnostic accuracy of this non-invasive approach was significantly higher than standard of care (Youden index 0.968 vs 0.707, P<0.0001), they noted in Clinical Cancer Research.

In addition, liquid biopsy reduced the time to diagnosis from a median of 41 days to 15 days, and estimated costs associated with this method were about 36% to 38% less than the traditional biopsy approach.

“Currently the way we diagnose HPV-associated cancer is either with a needle biopsy of a neck lymph node or a tissue biopsy from the oropharynx — and these approaches have a couple of different limitations,” Faden told MedPage Today. Not only are they invasive and painful for patients, but needle biopsy of a neck lymph node has high failure rates due to a lack of adequate cellular material.

“So, patients might have to undergo a repeat biopsy to get the diagnosis we are waiting for,” he noted. “That adds time to diagnosis, and we know that time from presentation to when patients start treatment impacts outcomes, so we want to start that as soon as possible.”

Considering these challenges, Faden and colleagues assessed a circulating tumor HPV DNA-based diagnostic approach compared with standard clinical workup.

They prospectively enrolled 70 patients presenting with a new or suspected diagnosis of HPV-associated oropharyngeal squamous cell carcinoma, nasopharyngeal carcinoma, or sinonasal squamous cell carcinoma, all of whom underwent standard-of-care diagnostic workup, as well as 70 control patients who were subsequently diagnosed with HPV-negative HNSCC.

Blood samples were collected and processed for circulating tumor HPV DNA, and analyzed with custom droplet digital PCR assays for HPV genotypes 16, 18, 33, 35, and 45.

Of the 70 patients in the HPV-positive group, 61 were available for analysis. Fine-needle aspiration was the first diagnostic approach in 37 patients, while primary tissue biopsy was the first for 24 patients. The overall diagnostic success rate on the first attempt was 72%, meaning that 17 patients (28%) had to undergo a repeat biopsy to achieve diagnosis.

Faden and colleagues also evaluated the diagnostic accuracy of liquid biopsy in combination with cross-sectional imaging and physical examination.

“We realized that people may be skeptical about making a diagnosis of cancer just off a blood test, and not having a traditional tissue biopsy,” Faden said. “In order to build confidence in having this non-invasive diagnosis, we took our liquid biopsy and combined it with routine things patients receive when they first present — a physical exam and cross-sectional imaging with either a CT or MRI scan.”

The researchers found that this approach yielded a specificity of 98.6%, but a sensitivity that was slightly lower (95.1%). “But this was because some patients lack classic imaging or physical exam findings, such as a mass you can see in the throat or enlarged lymph nodes in the neck,” he explained.

Faden and colleagues are preparing to open a trial designed to validate the findings from this study next year, and plan to use liquid biopsy to make real-time decisions for patients during treatment to personalize their care.

2021-12-03T05:54:26-07:00December, 2021|Oral Cancer News|

Etiglimab/Nivolumab combination shows promise in solid tumors

Source: www.targetedonc.com
Author: Sara Karlovitch

The combination of etigilimab, an anti-TIGIT antibody, in combination with nivolumab (Opdivio) has demonstrated anti-tumor efficacy and acceptable safety data in patients with solid tumors, according to a press release on the interim results of the phase 1b/2 ACTIVATE trial by Mereo BioPharma Group plc.

The phase 1b/2 study (NCT04761198) has a target enrollment of 125 participants and an estimated study completion date of June 2023. The primary end point is objective response rate.

During the study, patients will receive an infusion of etigilimab every 2 weeks and an infusion of nivolumab every 2 weeks. Cohorts include squamous cell carcinoma of the head and neck, cervical cancer on or after chemotherapy, gastric or gastroesophageal junction adenocarcinoma, endometrial carcinoma, tumor burden high and microsatellite stable solid tumors, rare disease with high TIGIT expression, ovarian cancer, and endometrial carcinoma post standard of care therapy.

At the time of data cutoff, 22 patients were included in the safety analysis. Twenty patients were evaluable with a minimum of at least one scan and 15 were included in the efficacy analysis.

The analysis found that 1 patient in the cervical cancer cohort had a complete response. In the ovarian cancer cohort, 1 patient had a partial response. Four patients with stable disease was seen in ovarian cancer, cervical cancer, and uveal melanoma. Additionally, the ovarian cancer cohort has crossed futility for expansion into the second stage of the study.

The combination was found to be well tolerated, and no new safety signals were observed. Common adverse events included skin reactions, which were seen in 7 patients. No patients required systemic steroids. There was one reported case of immune diabetes mellitus.

“These early results from the ACTIVATE study are highly encouraging and support the further study of etigilimab in combination with an anti-PD-1 antibody in solid tumor types, especially in gynecologic malignancies,” said Denise Scots-Knight, PhD, chief executive officer of Mereo in a press release. “We are particularly excited by the complete response in the cervical cancer cohort and the partial response in one of the ovarian cancer patients treated to-date. In the efficacy analysis set, biomarker analysis showed a positive trend between baseline PVR expression and clinical benefit including in the absence of PD-L1 expression in the efficacy analysis population. Clinical benefit also occurred in tumor types with historically low response rates to anti-PD-1/PDL-1 antibodies. We look forward to providing additional updates on the study in 2022.”

In order to participate in the study, patients must have a confirmed diagnosis of a relevant tumor type and are not candidates for curative surgery or radiation therapy, have available tumor tissue, adequate hematological and end organ function, life expectancy greater than 12 weeks, and an ECOG performance status of 0 to 1.

Patients with a concurrent active malignancy, major surgery within 4 week of treatment, active or suspected autoimmune disease, prior treatment with anti-TIGIT antibodies, a history of immune-related adverse events, active HIV infection, or are pregnant are not eligible to participate.

The study is currently recruiting in Arizona, California, Florida, Massachusetts, Michigan, Minnesota, New York, North Carolina, Oklahoma, Tennessee, Texas, Utah, and Virginia.

Mereo reports interim data from ACTIVATE Phase 1b/2 study of etigilimab. News release. Mereo. November 30, 2021. Accessed December 1, 2021. https://bit.ly/3d6dQgp

A study of etigilimab and nivolumab in subjects with locally advanced or metastatic tumors. ClinicalTrials.gov. Accessed December 1, 2021. https://bit.ly/3Eez47H

2021-12-02T08:25:04-07:00December, 2021|Oral Cancer News|

Geographic disparities in head and neck cancer survival in Upstate New York 2011-2019

Source: www.docwirenews.com
Author: DocWire News Featured Reading

This article was originally published here
Head Neck. 2021 Nov 29. doi: 10.1002/hed.26945. Online ahead of print.


PURPOSE: To examine the association between distance to care-center and urban-rural residence on 5-year overall survival (OS) from head and neck cancer (HNC).

MATERIALS AND METHODS: Five-year OS was retrospectively measured from date of initial diagnosis for patients with HNC treated at a single tertiary care center. Distances were calculated based on ZIP code of patient’s residence and care center. Multilevel Weibull regression was used to adjust for confounders and identify disparities in 5-year all-cause mortality.

RESULTS: A total of 670 patients included in study. Multivariable analysis revealed older age or late-stage cancer at diagnosis, and HPV negative status were associated with poorer OS. Patients residing in isolated small rural town (HR = 2.20, p = 0.015) or small rural town (HR = 2.07, p = 0.015) had lower OS. Distance to care center was not associated with OS (HR = 0.996, p = 0.11).

CONCLUSIONS: Greater rurality was associated with poorer OS among HNC patients in Upstate New York.

2021-12-01T15:19:36-07:00December, 2021|Oral Cancer News|

Treatment paradigms are shifting for locally advanced HPV-positive head and neck cancers

Source: www.onclive.com
Authors: Kaveh Zakeri, MD, MAS, Nancy Y. Lee, MD

The standard of care for patients with locally advanced head and neck squamous cell carcinomas does not substantially differ according to human papillomavirus (HPV) status in the National Comprehensive Cancer Network guidelines.1 Resectable tumors can be treated with surgery followed by adjuvant therapy. Alternatively, definitive chemoradiation therapy with cisplatin is the other dominant treatment paradigm. Incidence of HPV-associated oropharyngeal squamous cell carcinoma has increased rapidly and is associated with higher overall survival (OS) compared with cancers caused by smoking and alcohol.2,3 Given the unique biology of HPV-associated oropharyngeal disease, a separate staging system was developed for these tumors.4

HPV-associated oropharyngeal cancers are more radiosensitive and chemosensitive than cancers caused by smoking and alcohol, yet the traditional treatment paradigms—including high doses of radiation and chemotherapy—were developed prior to the epidemic of HPV-associated disease. De-escalation of therapy has been proposed for HPV-associated oropharyngeal cancer based on data demonstrating high OS and progression-free survival (PFS).5 De-escalation of therapy has been investigated for both definitive surgical and chemoradiation therapy paradigms. Most de-escalated approaches focus on selecting patients according to clinical features, such as disease stage and smoking status, whereas personalized de-escalation reduces treatment intensity for patients according to treatment response.

Transoral Robotic Surgery Followed by Adjuvant Radiotherapy
Transoral robotic surgery (TORS) is a minimally invasive approach that reduces morbidity compared with traditional, open surgery for patients with oropharyngeal cancers. TORS is a standard of care option for patients with resectable tonsil or base of tongue tumors when adequate functional outcome can be preserved. For patients with HPV-associated oropharyngeal disease, postoperative radiation is typically recommended for those with high-risk features including close or positive margins, lymphovascular invasion, perineural invasion, and involved lymph nodes. Adjuvant chemotherapy is recommended for patients with positive margins or lymph nodes with extracapsular extension. Standard doses of radiation consist of 50 to 60 Gy; standard adjuvant chemotherapy typically includes either high-dose or weekly cisplatin.

De-escalated postoperative treatment has been investigated, including reduced intensity of radiation and/or chemotherapy. De-escalation of adjuvant radiation therapy has involved both reduced dose and target volumes. ECOG-ACRIN 3311 (NCT01898494) was a randomized clinical trial in which investigators evaluated reduced dose adjuvant radiation therapy for patients with intermediate postoperative risk factors.6 Patients with low-risk pT1-T2, N0-1 disease with negative margins were observed. Patients with intermediate risk disease (close margins, < 1 mm of extranodal extension, 2 to 4 involved lymph nodes, perineural invasion, or lymphovascular invasion) were randomized to postoperative radiation of either 50 or 60 Gy. High-risk patients with positive margins, greater than 1 mm of extranodal extension, or more than 5 involved nodes received radiation with cisplatin. At a median follow-up of 35.1 months, the 3-year PFS rates were 96.9%, 94.9%, 93.5%, and 90.7% for the low-risk, 50 Gy, 60 Gy, and high-risk arms, respectively.6 Reduced doses of postoperative radiation and chemotherapy were also investigated in the single-arm MC1273 clinical trial (NCT01932697).7 Following surgery, patients received 30 to 36 Gy in 1.5-Gy twice-daily fractions with weekly docetaxel chemotherapy. The rates of 2-year locoregional control, PFS, and OS were 96.2%, 91.1%, and 98.7%, respectively, with 3 years of follow-up. The intensity of 30 to 36 Gy given twice daily compared with the standard 50 to 60 Gy given once daily is unclear.8 Randomized clinical trials are needed to determine whether the MC1273 treatment regimen results in noninferior cure rates with reduced toxicity compared with standard therapy. The PATHOS trial (NCT02215265) is an ongoing randomized clinical trial investigating a reduction in adjuvant radiation and chemotherapy.9 Patients with low-risk disease are observed postoperatively, patients with intermediate risk factors are randomized to 50 Gy vs 60 Gy, and patients with high-risk features are randomized to 60 Gy alone or 60 Gy with cisplatin. An additional postoperative de-escalation strategy involves omission of the primary site (tonsil or base of tongue) for patients without primary site risk factors for recurrence (perineural invasion, lymphovascular invasion, or close surgical margins).10 The AVOID trial (NCT02159703) was a single-arm study of adjuvant radiotherapy to the neck alone in patients without primary site risk factors. In total, 60 patients were enrolled and at 2.4 years of median follow-up, only 1 patient had a primary site recurrence. Although this strategy appears promising, more work is necessary to validate these findings and determine the long-term risks and benefits of this approach. Collectively, these clinical trials demonstrate that TORS followed by adjuvant radiation with or without chemotherapy results in high rates of tumor control. Reduced doses of postoperative radiation and chemotherapy appear promising as a strategy to reduce toxicity while maintaining high rates of cure, and clinical trials investigating these approaches are ongoing. Two randomized clinical trials have compared TORS plus adjuvant therapy with definitive chemoradiation—the ORATOR trial (NCT01590355) and the ORATOR2 trial (NCT03210103).11,12 The phase 2 ORATOR trial was designed to determine whether TORS would improve 1-year swallowing quality of life. After 25 months of follow-up, patients treated with radiation had a statistically significant improvement in swallowing quality of life, but the difference did not meet the prespecified threshold of clinical significance. There was no difference in PFS or OS between the groups. The follow-up ORATOR2 study randomized patients to de-escalated radiation-based treatment vs surgery with de-escalated adjuvant therapy.12 The results are pending release. Additional studies are needed to determine the differences between surgery and radiation-based paradigms for treatment of HPV-associated oropharyngeal disease.

Definitive Radiotherapy With Chemotherapy Cetuximab and/or Immunotherapy
Definitive radiotherapy with high-dose cisplatin is the alternative to TORS-based approaches and is standard for unresectable HPV-associated oropharyngeal tumors. In an attempt to reduce the toxicity of treatment, cetuximab (Erbitux) was proposed as an alternative to cisplatin chemotherapy. Three randomized phase 3 trials compared cisplatin/radiotherapy with cetuximab/radiotherapy: RTOG 1016 (NCT01302834), De-ESCALaTE HPV (NCT01874171), and TROG 12.01 (NCT01855451). Investigators of all 3 trials observed a statistically significant detriment in either PFS or OS for patients treated with cetuximab/radiation (Table).13-15 Additionally, toxicity was not reduced with cetuximab compared with cisplatin.

Omission of systemic therapy with radiation was studied in the randomized phase 2 NRG-HN002 trial (NCT02254278). Patients with p16-positive, nonmetastatic, T1-T2 N1-N2b or T3 N0-N2b (7th edition staging) oropharynx cancer with 10 or fewer pack-years of smoking were randomized to 60 Gy of radiation in 6 weeks with cisplatin vs 60 Gy of radiation in 5 weeks without any systemic therapy. The 2-year PFS rate was 90.5% for cisplatin/radiation vs 87.6% for radiation alone. The radiation alone arm did not meet the prespecified threshold for PFS superiority to 85%. There was no difference in swallowing quality of life between the 2 arms.16

Several randomized trials have investigated the role of immune checkpoint inhibitors (ICIs) in combination with definitive radiation therapy for HPV-associated oropharyngeal cancer. Immunotherapy has been proposed as an alternative to cisplatin for patients with favorable-risk disease and as an additive treatment to cisplatin/radiation for patients with high-risk disease. In patients with favorable-risk disease, the goal of replacing cisplatin with immunotherapy is to reduce the toxicity of treatment while maintaining high cure rates. Investigators are testing this strategy (NRG-HN005, CCTG HN.9 [NCT03410615], and KEYCHAIN [NCT03383094]) and have incorporated ICIs such as nivolumab (Opdivo), durvalumab (Imfinzi), tremelimumab, and pembrolizumab (Keytruda) into the radiation-based treatment paradigm.17-19

For patients with high-risk disease, ICIs have been added to the cisplatin/radiation backbone. Investigators of the randomized phase 3 JAVELIN HEAD AND NECK 100 trial (NCT02952586) evaluated the addition of avelumab (Bavencio) to cisplatin/radiotherapy and included patients with high-risk HPV-associated oropharynx cancer. There was no improvement in PFS with the addition of avelumab to cisplatin/radiotherapy.20 Additionally, investigators of the randomized phase 3 Groupe Oncologie Radiotherapie Tete et Cou REACH trial (NCT02999087) did not observe a benefit with radiation/avelumab/ cetuximab vs cisplatin/radiation.21

These randomized clinical trials highlight the importance of radiosensitizing cisplatin in combination with radiation therapy. Replacement of cisplatin with cetuximab and omission of cisplatin led to inferior tumor control without improvements in toxicity. For patients with high-risk disease, immunotherapy has not demonstrated a benefit when added to cisplatin/radiation or radiation/cetuximab. For patients with favorable-risk disease, ongoing clinical trials will determine whether there is a role for radiation/ immunotherapy.

Personalized Chemoradiation Therapy Based on Hypoxia Imaging
Personalized treatment strategies involve tailoring the intensity of radiation and chemotherapy to individual patient biology and tumor response. Among patients with HPV-associated oropharyngeal cancer, there is heterogeneity in tumor biology and resistance to treatment.22-24 Nonpersonalized treatment paradigms including omission of systemic therapy and replacement of cisplatin with cetuximab were unsuccessful, potentially because differences in tumor biology were not accounted for. Personalized treatment according to tumor biology may facilitate successful tailoring of treatment intensity. Tumor hypoxia is associated with radioresistance and inferior locoregional control and OS in head and neck cancer.25,26

18F-fluoromisonidazole (18F-FMISO) positron emission tomography (PET) is a novel method of measuring tumor hypoxia in vivo and can predict treatment outcomes in patients with head and neck cancer.27 De-escalation of radiation and chemotherapy based on tumor hypoxia using 18F-FMISO PET is a promising treatment strategy for HPV-associated oropharynx cancer. An initial pilot study at Memorial Sloan Kettering Cancer Center in New York, New York, demonstrated successful de-escalation to 60 Gy of radiation with cisplatin for patients with resolution of hypoxia according to 18F-FMISO PET imaging.28 Among the 33 enrolled patients, the 2-year locoregional control and OS rates were 100%.

The subsequent 30 ROC trial (NCT03323463) also conducted by investigators at Memorial Sloan Kettering Cancer Center investigated whether a dramatic reduction in radiation dose to 30 Gy with high-dose cisplatin or carboplatin with 5-fluorouracil could result in successful de-escalation. Patients had resection of the primary tumor prior to chemoradiation and planned neck dissection at 4 months post chemoradiation to measure pathologic response. Patients with resolution of hypoxia on 18F-FMISO PET imaging were treated to 30 Gy with 2 cycles of chemotherapy. Among the 19 enrolled patients, the 2-year rates of locoregional control and OS were 94.4% and 94.7%, respectively.29

Phase 2 of the 30 ROC trial examined the same strategy of resection of the primary tumor followed by 30 Gy of radiation and 2 cycles of chemotherapy with omission of planned neck dissections. The rates of 1-year locoregional control, distant metastasis-free survival, and OS were 94%, 100%, and 100%, respectively, at median follow-up of 1 year.30 All 8 reported local recurrences were in the neck and successfully salvaged with surgery. A subsequent phase of the 30 ROC trial is ongoing with omission of both resection of the primary tumor and planned neck dissection.

Next Steps in the Field
The standard-of-care treatment paradigms for patients with locally advanced HPV-associated head and neck cancer include up-front surgery followed by adjuvant radiation with or without chemotherapy and definitive radiation with cisplatin. De-escalation of postoperative adjuvant therapy is the subject of investigation. Replacement of cisplatin with cetuximab or omission of cisplatin with definitive radiotherapy have not been successful. The addition of immunotherapy to definitive radiation-based treatment has not demonstrated a benefit thus far. A personalized treatment paradigm based on hypoxia imaging is promising and may yield a successful, personalized de-escalation strategy for patients with HPV-associated oropharynx cancer.

Kaveh Zakeri, MD, MAS, is a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York, New York.

Nancy Y. Lee, MD, is vice chair of the Department of Radiation Oncology, service chief of head and neck radiation oncology, and service chief of proton therapy at Memorial Sloan Kettering Cancer Center in New York, New York.

1. NCCN. Clinical Practice Guidelines in Oncology. Head and neck cancers, version 3.2021. Accessed October 29, 2021. https://www.nccn.org/professionals/physician_gls/ pdf/head-and-neck.pdf
2. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. doi:10.1056/NEJMoa0912217
3. Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294- 4301. doi:10.1200/JCO.2011.36.4596
4. O’Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17(4):440-451. doi:10.1016/S1470-2045(15)00560-4
5. Adelstein DJ, Ismaila N, Ku JA, et al. Role of treatment deintensification in the management of p16+ oropharyngeal cancer: ASCO provisional clinical opinion. J Clin Oncol. 2019;37(18):1578-1589. doi:10.1200/JCO.19.00441
6. Ferris RL, Flamand Y, Weinstein GS, et al. Updated report of a phase II randomized trial of transoral surgical resection followed by low-dose or standard postoperative therapy in resectable p16+ locally advanced oropharynx cancer: a trial of the ECOG-ACRIN cancer research group (E3311). J Clin Oncol. 2021;39(suppl 15):6010. doi:10.1200/ JCO.2021.39.15_suppl.6010
7. Ma DJ, Price KA, Moore EJ, et al. Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiotherapy in human papillomavirus-associated oropharynx squamous cell carcinoma. J Clin Oncol. 2019;37(22):1909-1918. doi:10.1200/ JCO.19.00463
8. Garden AS. Not all 30-Gy regimens are equal. J Clin Oncol. 2019;37(36):3558-3559. doi:10.1200/JCO.19.01666
9. Owadally W, Hurt C, Timmins H, et al. PATHOS: a phase II/III trial of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery for human papillomavirus (HPV) positive oropharyngeal cancer. BMC Cancer. 2015;15:602. doi:10.1186/s12885-015-1598-x
10. Swisher-McClure S, Lukens JN, Aggarwal C, et al. A phase 2 trial of alternative volumes of oropharyngeal irradiation for de-intensification (AVOID): omission of the resected primary tumor bed after transoral robotic surgery for human papilloma virus–related squamous cell carcinoma of the oropharynx. Int J Radiat Oncol Biol Phys. 2020;106(4):725-732. doi:10.1016/j.ijrobp.2019.11.021
11. Nichols AC, Theurer J, Prisman E, et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol. 2019;20(10):1349-1359. Published correction appears in Lancet Oncol. 2019;20(12):e663.
12. Nichols AC, Lang P, Prisman E, et al. Treatment de-escalation for HPV-associated oropharyngeal squamous cell carcinoma with radiotherapy vs. trans-oral surgery (ORATOR2): study protocol for a randomized phase II trial. BMC Cancer. 2020;20(1):125. doi:10.1186/s12885-020-6607-z
13. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. Published correction appears in Lancet. 2020;395(10226):784.
14. Mehanna H, Robinson M, Hartley A, et al; De-ESCALaTE HPV Trial Group. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. doi:10.1016/S0140-6736(18)32752-1
15. Rischin D, King M, Kenny L, et al. Randomized trial of radiotherapy with weekly cisplatin or cetuximab in low-risk HPV-associated oropharyngeal cancer (TROG 12.01) – a Trans-Tasman Radiation Oncology Group study. Int J Radiat Oncol Biol Phys. 2021;111(4):876-886. doi:10.1016/j.ijrobp.2021.04.015
16. Yom SS, Torres-Saavedra P, Caudell JJ, et al. Reduced-dose radiation therapy for HPV-associated oropharyngeal carcinoma (NRG Oncology HN002). J Clin Oncol. 2021;39(9):956-965. doi:10.1200/JCO.20.03128
17. Spreafico A, Sultanem K, Chen B, et al. A randomized phase II study of cisplatin plus radiotherapy versus durvalumab plus radiotherapy followed by adjuvant durvalumab versus durvalumab plus radiotherapy followed by adjuvant tremelimumab and durvalumab in intermediate risk, HPV-positive, locoregionally advanced oropharyngeal squamous cell cancer (LA-OSCC) (Canadian Cancer Trials Group HN.9). Ann Oncol. 2018;29(suppl_8):VIII399. doi:10.1093/annonc/mdy287.080
18. De-intensified radiation therapy with chemotherapy (cisplatin) or immunotherapy (nivolumab) in treating patients with early-stage, HPV-positive, non-smoking associated oropharyngeal cancer. ClinicalTrials.gov. Updated October 26, 2021. Accessed October 29, 2021. https://clinicaltrials.gov/ct2/show/NCT03952585
19. Chemoradiation vs immunotherapy and radiation for head and neck cancer. ClinicalTrials.gov. Updated October 8, 2021. Accessed October 29, 2021. https://clinicaltrials. gov/ct2/show/NCT03383094
20. Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470- 2045(20)30737-3
21. Bourhis J, Tao Y, Sun X, et al. Avelumab-cetuximab-radiotherapy versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): randomized phase III GORTEC-REACH trial. Ann Oncol. 2021;32(suppl 5):S1283-S1346. doi:10.1016/annonc/annonc741
22. Kimple RJ, Smith MA, Blitzer GC, et al. Enhanced radiation sensitivity in HPV-positive head and neck cancer. Cancer Res. 2013;73(15):4791-4800. doi:10.1158/0008-5472.CAN-13-0587
23. Vainshtein J, McHugh JB, Spector ME, et al. Human papillomavirus-related oropharyngeal cancer: HPV and p16 status in the recurrent versus parent tumor. Head Neck. 2015;37(1):8-11. doi:10.1002/hed.23548
24. Rieckmann T, Tribius S, Grob TJ, et al. HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol. 2013;107(2):242-246. doi:10.1016/j.radonc.2013.03.013
25. Terris DJ. Head and neck cancer: the importance of oxygen. Laryngoscope. 2000;110(5 Pt 1):697-707. doi:10.1097/00005537-200005000-00001
26. Brizel DM, Dodge RK, Clough RW, Dewhirst MW. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999;53(2):113-117. doi:10.1016/s0167-8140(99)00102-4
27. Rasey JS, Koh WJ, Evans ML, et al. Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Int J Radiat Oncol Biol Phys. 1996;36(2):417-428. doi:10.1016/s0360-3016(96)00325-2
28. Lee N, Schoder H, Beattie B, et al. Strategy of using intratreatment hypoxia imaging to selectively and safely guide radiation dose de-escalation concurrent with chemotherapy for locoregionally advanced human papillomavirus-related oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2016;96(1):9-17. doi:10.1016/j.ijrobp.2016.04.027
29. Riaz N, Sherman E, Pei X, et al. Precision radiotherapy: reduction in radiation for oropharyngeal cancer in the 30 ROC trial. J Natl Cancer Inst. 2021;113(6):742-751. doi:10.1093/jnci/djaa184
30. Lee NY, Sherman EJ, Schöder H, et al. The 30 ROC trial: precision intra-treatment imaging guiding major radiation reduction in human papillomavirus related oropharyngeal cancer. J Clin Oncol. 2021;39(suppl 15):6019. doi:10.1200/JCO.2021.39.15_suppl.6019

2021-11-23T08:16:08-07:00November, 2021|Oral Cancer News|

Oral cancer and COVID-19

Source: dentistry.co.uk
Author: Seb Evans

The Dental Defence Society explain how COVID-19 has impacted the detection of oral cancer and what dental teams should do to improve outcomes.

Referrals for oral cancer have fallen dramatically since the start of the pandemic. This is raising fears that many cases have gone undiagnosed because of disruption to routine dental care.

Missed opportunities for early detection mean it is likely that thousands of patients will eventually present with late-stage disease and poor prognosis. They will also require aggressive and complex treatments that diminish their quality of life. As well as adding to the burden on the healthcare system.

Now more than ever, dental teams must prioritise the prevention, early detection and rapid referral of oral cancer.

They will play a vital role in mitigating the ongoing impact of the pandemic on outcomes for this cancer through performing examinations at every opportunity, recognising when a patient presents with signs and symptoms, and raising awareness.

Increasing burden of oral cancer in the UK
The most recent figures on mouth cancer in the UK align with the global trend. They shows an alarming rise in incidence and mortality.

The State of Mouth Cancer UK Report 2020/21 reports that last year 8,722 people were diagnosed with mouth cancer. And an estimated 2,702 people died from the disease. That’s up 58% and 48%, respectively, from a decade ago.

Early detection and rapid referral for treatment makes a huge difference for patients with oral cancer. It boosts survival from 50% to 90%.

But even before the pandemic, most patients were diagnosed at a late stage. This means they need aggressive treatments and experience poor clinical outcomes.

Why are outcomes so poor? Patients are often unaware of oral cancer and its symptoms. So they seek help late.

Clinicians do not perform enough soft tissue examinations. And many patients do not attend regular dental appointments; either through choice or because of limited access.

Impact of COVID-19 on oral cancer
The COVID-19 crisis has only worsened the situation by disrupting routine dental care.

Although dental practices have re-opened, capacity is still well below pre-COVID levels.

While dentists focus on urgent treatments, they may not check for signs and symptoms of oral cancer.

According to one of England’s biggest NHS Trusts, referrals fell by 65% after the beginning of lockdown. This suggests that thousands of patients are living with undiagnosed oral cancers. And we’re therefore missing opportunities for early detection.

The pandemic may also have a long-term impact on the incidence of oral cancer.

During lockdowns, some people engaged more often in behaviours that are known risk factors. Such as smoking and excess drinking.

School closures also interrupted full delivery of vaccination against human papillomavirus (HPV), another important risk factor.

Dental teams have a vital role in improving oral cancer outcomes
A huge effort is needed to stem the rise in cases of oral cancer and improve outcomes for patients. Dental teams will play a leading role by providing:

  • Intra- and extra-oral examinations at every opportunity. During routine check-ups and treatment appointments. Provide rapid access to an oral examination for patients with suspected lesions who are referred by local GPs or pharmacists
  • Urgently refer patients with suspected lesions to secondary care via the suspected cancer pathway. Have protocols in place and follow the relevant guidance, eg from NICE or NHS Scotland
  • Patient education.Raise awareness of oral cancer, associated risk factors, the signs and symptoms and the importance of early detection. Make information available to patients through websites, printed resources and other communications
  • Information on self-examination. Support patients to examine themselves for early signs of oral cancer. Provide information about how to do this and the symptoms to look out for. Emphasise the importance of reporting symptoms early. The Mouth Cancer Foundation website includes useful information and downloads
  • Support for Mouth Cancer Action Month. Get involved in this campaign run by the Oral Health Foundation each November; resources are available on the website
  • Support for the HPV vaccination campaign.Encourage anyone eligible to have the HPV vaccination when offered it.

Dentists must remain vigilant and keep up-to-date
To ensure the best care for patients with oral cancer, it is vital that dental clinicians remain vigilant in checking and referring according to clinical guidelines.

From a dentolegal perspective, it is important to keep detailed records. Include both positive and negative findings from intra- and extra-oral examinations.

Dentists should maintain an up-to-date knowledge of oral cancer and how to detect it.

The BDA provides a valuable oral cancer toolkit, developed in partnership with Cancer Research UK. As well as a number of courses and webinars on the topic. BDA Scotland also offers resources on oral cancer.

2021-11-21T09:53:43-07:00November, 2021|Oral Cancer News|

Detecting suspicious lesions: what do I say next?

Source: dentistry.co.uk
Author: Philip Lewis

Dental team members are amazing. They put patients at their ease and provide treatment for their dental issues. They improve smiles, boost self-confidence and they save lives.

Yes, you read that right. There aren’t many opportunities for dental team members to be lifesavers. Detecting mouth cancer at an early stage is one of them. It’s an initiative for the whole dental team. Both clinical and non-clinical team members have a vital part to play.

From a receptionist noticing changes in a patient’s voice, a practice manager spotting a swelling they haven’t seen before to a clinician picking up on a soft-tissue abnormality, we all get the chance to be pivotal in protecting a patient’s wellbeing.

Risk factors
We know there are risk factors we should be aware of: the use of tobacco in any form, regular use of alcohol, especially spirits, social deprivation with its associated problems of nutrition and vitamin deficiency.

It is understood that increasing age is a factor and that men are more likely than women to get the disease. We appreciate the significant effects of infection that certain strains of HPV have had recently but realise how important it is to examine all adults. Many sufferers have no identifiable risk factors.

During the clinical examination, we’ll be looking for anything unusual, including:

  • Red, white or mixed patches
  • Ulcers that don’t heal within a maximum of three weeks
  • Swellings
  • Changes to normal appearance or texture and lumps in the face or neck discovered during palpation.

We’ll carefully check the medical history. A number of commonly-prescribed medicines can cause swellings, ulceration or other changes within the mouth. Abnormalities can also be due to formerly-diagnosed conditions like lichen planus, scar tissue following surgery or various systemic conditions.

What if we find something we think might be serious; something we feel needs a specialist opinion? It’s easy enough to send a referral, but what are we going to tell the patient?

Wise words
Cancer is still a scary word. It’s reassuring to know that the vast majority of patients we send through rapid referral pathways turn out not to have mouth cancer, but some are less lucky.

It’s essential we prepare our patients in advance for that possibility, however unlikely.

They say anything we tell a patient before an event is information, anything we tell them afterwards is an excuse.

That’s why it’s important to give information even before the examination. Non-clinical team members can do this when properly trained.

Patients need to know an examination is going to take place, why we are doing it and precisely how the examination will be carried out.

We can point out facts like how mouth cancer is on the increase when most other major cancers reduce in incidence each year.

Early detection
We can explain how important early detection is. Also, how this reduces the amount of treatment needed compared to when cancer is discovered at a later stage.

We can state how early detection vastly improves the chances of long-term survival.

We need to let our patients know the nature of the procedure; especially as it includes palpation of the face and neck, which they might otherwise find strange in a dental setting.

We have to inform them that unusual words we might use are simply technical descriptions and do not imply problems.

We must stress that we carry out these examinations for all our adult patients as part of the practice’s commitment to providing the best possible service for everyone.

Remind them that we are not solely concerned with teeth, but look after everybody’s general health and wellbeing whenever possible.

As well as giving this sort of general information, we have to point out that sometimes a clinician will feel the need to take another look at an area in a few weeks’ time, or want to gain a second opinion from a specialist colleague.

We must stress the importance of attending such a follow-up appointment and, again, impress upon the patient that we are doing this to ensure that we are serving their best interests.

The right approach
Throughout our discussions we have to maintain a supportive and sympathetic manner.

We do not wish to alarm or distress patients. However, we do need them to understand the importance of our actions and the necessity for them to comply with our recommendations.

Trivialising the situation by making statements such as ‘it’s probably nothing’ or ‘it doesn’t look serious to me’ will not be helpful if a positive diagnosis is subsequently made and may cause a patient to lose trust in the practice.

It is better to say: ‘There are many possible causes for what I have found. I have specialist colleagues who are extremely experienced in diagnosing the cause of this sort of thing and I think it would be wise for you to go and get a second opinion.’

Patients should always feel free to ask questions about their treatments or investigations.

A common question when we’ve found an abnormality and brought it to a patient’s attention is: ‘What do you think it is?’

In this event, depending on what has been discovered, we can describe a number of possible causes for what we are looking at. However, we do have to explain there is a possibility that the abnormality has been caused by cancer; indeed, some rapid referral pathways insist that this information has been given before they will accept a referral.

Human nature dictates that people will often fear the worst. Until they receive a confirmation of diagnosis, they will feel uneasy and apprehensive.

Throughout this period, dental team members need to continue with a gentle and caring approach, promptly answering any further questions and providing more information and support.

Bottom line
As mentioned, most suspicious cases we refer will turn out not to be mouth cancer. Those that are will set patients upon a treatment and management pathway that is a subject for other articles.

The bottom line is that early detection and timely referrals save lives. Not only lives, but also the quality of life both for sufferers and everyone around them. A few verbal skills can mean the difference between a patient accepting early treatment or not.

With early detection, a patient’s chances of 10 year-plus survival are more than 80% compared with just 18% for late detection.

If you or one of your team members is responsible for a patient’s early detection that potentially saves their life, you won’t only be considered their dental practice, you’ll be considered their heroes!

2021-11-19T07:02:03-07:00November, 2021|Oral Cancer News|

Improving the management of HNSCC: next steps

Source: www.cancernetwork.com
Author: Victoria Meucci Villaflor, MD, Cesar Perez, MD

Dr Cesar Perez reacts to the utilization of next-generation sequencing in head and neck squamous cell carcinoma and highlights future areas of study. Video of interview here.

Victoria Meucci Villaflor, MD: With solid tumor oncology moving more toward precision medicine or personalized medicine, where do you think head and neck cancer is going?

Cesar Perez, MD: The data that we discussed from the RUN-HN trial have shown us that there’s a role for personalized medicine in head and neck cancer. We’ve seen more value in sequencing for this population that we weren’t finding much before, besides checking for PD-L1 by immunohistochemistry. Next-generation sequencing probably has a new role in this disease. I hope that this is just the tip of the iceberg of what we can accomplish by doing sequencing on our patients with head and neck cancer.

Victoria Meucci Villaflor, MD: Dr Perez, are you using next-generation sequencing on all of your patients with head and neck cancer?

Cesar Perez, MD: Yes. Until recently, we weren’t finding that much value in doing next-generation sequencing in patients with head and neck squamous cell carcinoma. But based on all the trials in clinical development, I’m now doing next-generation sequencing on every patient in the metastatic and recurrent setting to find those patients with a high TMB [tumor mutational burden], for example, who might not have good PD-L1. But I’m mainly doing it for clinical trial purposes, so we can then try to find driver mutations where we can put the patients on clinical studies, as they did with this trial on tipifarnib in patients with HRAS mutations.

Victoria Meucci Villaflor, MD: At City of Hope, we also sequence all of our metastatic patients as they come in. It would be fair to say that we gather some information out of this, even though it’s early in the development in squamous cell head and neck cancers, at least as far as putting patients on clinical trials.

Cesar Perez, MD: Definitely. That’s the way to go. We need to find options for this population beyond the approved options. The only way to do that is trying to sequence more patients and offering novel clinical studies to this population. That’s what they deserve.

Victoria Meucci Villaflor, MD: What do you feel are the important next steps?

Cesar Perez, MD: We have the data from the trial with tipifarnib for patients with HRAS mutations, and I feel that they are exciting data. It’s a small study. That’s what we need. We just need a larger trial that confirms this finding, and that is what’s being done right now with the AIM-HN study—the head and neck AIM study—in which tipifarnib is being studied in patients with head and neck squamous cell carcinoma with HRAS mutations. They also have a second cohort, an observational cohort, to analyze the effect of the first main therapy on patients with or without HRAS mutations. That trial is a lot larger than this. More than 200 patients are trying to enroll. That’s a multicenter worldwide trial. That’s definitely the next step. We want to see confirmatory and positive data, and that’s what they’re working on.

Victoria Meucci Villaflor, MD: What are the next clinical trials to build on the work that’s already been done in this arena?

Cesar Perez, MD: Obviously that trial, but we need to try to extend the benefit of these agents to a larger population. Trying to extend the benefit of the farnesyltransferase inhibitor toward a larger population is the way to go. You’re probably familiar with the KURRENT trial. What do you think about that approach, trying to give tipifarnib with a PIK3CA inhibitor for a larger population that we have been trying to treat for a long time with targeted therapy?

Victoria Meucci Villaflor, MD: That’s a very interesting concept. Often, many of these tumors are able to escape some of these inhibitors because they’ll go upstream or downstream to somehow circumvent the mechanism of action and can become resistant to it. I found a lot of the in vitro and early in vivo work looking at alpelisib and tipifarnib in the KURRENT trial very interesting and promising. I’m looking forward to seeing results of this in human subjects.

Cesar Perez, MD: Yes, I agree. PIK3CA is a way more common genomic abnormality in head and neck cancer. The exciting thing is that with the relationship between HRAS and PIK3CA being downstream, blocking the 2 pathways, as we have done in melanoma with BRAF and MEK, has been a success story. Doing it in head and neck is the way to go. As we have discussed before, PIK3CA alone is not going to cut it for a patient with head and neck cancer. But both the farnesyltransferase inhibitor and trying to block that HRAS escape route, and then blocking it with alpelisib—a drug that we already know is active in patients with breast cancer with PIK3CA mutated tumors—is the way to go. I’m excited about it. It’s a very smart approach to try to treat this disease.

Victoria Meucci Villaflor, MD: All in all, head and neck cancer is finally beginning to get into a situation where we’re able to target a lot of these molecules, and I’m looking forward to the years ahead where we’ll probably be able to target even more molecules. And looking at the different combinations in an effort to circumvent a lot of resistance mechanisms will also be a lot of work that’s to come for us.

Cesar Perez, MD: Definitely. In a couple of years, we’ll see sequencing have greater value. We’re able to inhibit and treat tumors with those specific genomic abnormalities. Then sequencing will be considered a must, as it is with patients with non–small cell lung cancer who you treat every day. It’s very exciting, and I’m hoping that these studies will bring some light to how to benefit and improve survival for this population that is in so much need.

Victoria Meucci Villaflor, MD: What would be your testing recommendations to other oncologists who might not specialize in head and neck cancer like us?

Cesar Perez, MD: We first need to acknowledge that we have a marker now. It’s been proven in an early trial that it’s potentially active. We need to put the word out that patients with neck and head cancer need to be tested. There needs to be sequencing of patients with head and neck cancer. There are potential options out there that are very promising, but the only way to try to put the patients on trial and prove that is doing the testing. We have to extend all these efforts in testing from other tumors into the head and neck cancer world and put the word out that this trial, RUN-HN, was at least a very promising strategy that gave us some data. They’re early data, but we have some data. We certainly should start testing all these patients, like you guys do at City of Hope and we do here at the Sarah Cannon Research Institute at Florida Cancer Specialists.

2021-11-18T08:38:14-07:00November, 2021|Oral Cancer News|

Two markers help predict head and neck cancer prognosis

Source: labblog.uofmhealth.org
Author: news release, University of Michigan Health Rogel Cancer Center

A new study from the University of Michigan Health Rogel Cancer Center finds circulating tumor DNA, or ctDNA, levels can predict as early as two weeks after starting treatment which patients are likely to have good outcomes.

At the same time, specialized MRI and PET scans two weeks after starting chemoradiation also correlated with outcomes.

“Rates of throat cancer have steadily increased in recent years, driven by HPV infections, fueling the need for biomarkers to help guide treatment decisions, especially for locally advanced disease,” said senior study author J. Chad Brenner, Ph.D., associate professor of otolaryngology at Michigan Medicine.

“Quantitative imaging of metabolism, local blood volume density and cell density from PET and MRI scans have shown both prognostic value in predicting treatment outcome as well as utility in selecting patients for additional focal radiation treatment,” said study author Yue Cao, Ph.D., professor of radiation oncology and radiology at Michigan Medicine.

The researchers conducted a randomized trial of patients with stage 3 oropharyngeal squamous cell carcinoma. In total, 93 patients had imaging and 34 also had blood tests before starting chemoradiation and again at two, four and seven weeks after treatment.

The study found that HPV ctDNA clearance at two weeks, but not at four weeks, predicted outcomes. The metabolism, local blood density and cell density before radiation therapy or at two weeks after starting treatment predicted outcomes as well. These early predictor biomarkers could help determine which patients need more aggressive treatment. A larger study is needed.

Funding for this work was from National Cancer Institute grants U01CA183848, R01CA184153 and P30CA046592.
The University of Michigan has filed a patent on the HPV ctDNA assay that was used in this paper.

Paper cited:
“Early HPV ctDNA Kinetics and Imaging Biomarkers Predict Therapeutic Response in p16+ Oropharyngeal Squamous Cell Carcinoma,” Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-21-2338

2021-11-17T07:43:52-07:00November, 2021|Oral Cancer News|

Most men benefit from initial and catch-up cancer prevention vaccination

Source: www.precisionvaccinations.com
Author: Don Ward Hackett

The Lancet Infectious Disease published the results from an extensive cancer prevention phase 3 study on November 12, 2021, supporting quadrivalent HPV vaccination in men, including catch-up vaccinations.

The Gardasil quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in men aged 16–26 years.

The researchers assessed the incidences of external genital warts related to HPV6 or 11 and external genital lesions and anal dysplasia associated with HPV6, 11, 16, or 18, over ten years of follow-up.

The 3-year Base Study was an international, double-blind, randomized, placebo-controlled trial done at 71 sites in 18 countries.

The Vaccination Period for the Base Study encompassed Day 1 through Month 7, during which time participants received qHPV vaccination at Day 1, Month 2, and Month 6. Follow-up for the Base Study encompassed Month 7 through Month 36.

And the 7-year, open-label, long-term follow-up extension study was done at 46 centers in 16 countries.

Between August 2010 and April 2017, 1,803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group.

In early vaccine group participants during long-term follow-up compared with the placebo group in the Base Study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0–8·7) versus 137·3 (83·9–212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0–7·7) versus 140·4 (89·0–210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5–114·4) versus 906·2 (553·5–1399·5).

Compared with during the Base Study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 vs. 0 cases per 10 000 person-years or external genital lesions associated with HPV6, 11, 16, or 18 vs. 0 cases per 10 000 person-years, and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 vs. 101·3 cases per 10 000 person-years.

Furthermore, there were no vaccine-related serious adverse events reported.

Gardasil is endorsed by the WHO, which says HPV vaccination prevents certain cancers by preventing infection by various HPV types.

This study was funded by Merck Sharp & Dohme, the producer of the Gardasil HPV vaccine.

In the U.S., the American Cancer Society’s updated recommendations are for healthcare providers to routinely offer the HPV vaccine series to boys and girls between ages 9 and 12.

Furthermore, the Gardasil 9 vaccine is offered in the U.S. It consists of HPV proteins, Types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

HPV infections can lead to certain cervical cancers. Many females with cervical cancer were probably exposed to cancer-causing HPV types in their teens and early 20s. Additionally, males can get HPV, causing anal and throat cancers and genital warts.

2021-11-16T08:57:09-07:00November, 2021|Oral Cancer News|

FDA grants priority review to first-line Toripalimab regimen in advanced nasopharyngeal carcinoma

Source: www.cancernetwork.com
Author: Hayley Virgil

A priority review was granted to toripalimab by the FDA for 2 indications in patients with advanced nasopharyngeal carcinoma.

A biologics license application (BLA) for the combination of toripalimab (Tuoyi) plus gemcitabine and cisplatin for patients with advanced recurrent or metastatic nasopharyngeal carcinoma was accepted by the FDA and granted priority review, according to a press release from developer Junshi Biosciences.1 The BLA also covered the use of toripalimab monotherapy for the treatment of recurrent or metastatic disease following a platinum-containing regimen in the second line and beyond.

The application for the anti–PD-1 monoclonal antibody is supported by findings from both the phase 2 POLARIS-02 trial (NCT02915432), which assessed toripalimab in previously treated and recurrent or metastatic nasopharyngeal carcinoma, and the phase 3 JUPITER-02 trial (NCT03581786), examining gemcitabine and cisplatin with or without toripalimab in recurrent of metastatic nasopharyngeal carcinoma.2,3 POLARIS-02 revealed durable clinical responses in those treated with toripalimab and JUPITER-02 identified notable improvements in progression-free survival (PFS).

The Prescription Drug User Fee Act action date is currently set for April 2022.

“We are excited by the continued progress of toripalimab toward a first marketing authorization outside of China,” Patricia Keegan, chief medical officer at Junshi Biosciences, said in a press release. “With the earlier approval in China, toripalimab became the world’s first immune checkpoint inhibitor for the treatment of nasopharyngeal carcinoma, bringing a novel therapy to a disease that has long lacked new drug development. We will cooperate closely with our partner, Coherus, to leverage the FDA’s Priority Review designation to accelerate the completion of the BLA review and believe toripalimab, if approved, will bring an important new treatment option for NPC patients in the United States.”

Patients enrolled on the POLARIS-02 trial received 3 mg/kg of intravenous toripalimab once every 2 weeks until experiencing disease progression or unacceptable toxicity. In the population of 190 patients, investigators reported an overall response rate of 20.5%, including a median duration of response of 12.8 months. Additionally, patients experienced a median PFS of 1.9 months and a median overall survival (OS) of 17.4 months.

A regimen consisting of either 240 mg of toripalimab and gemcitabine plus cisplatin every 3 weeks for 6 treatment cycles followed by subsequent toripalimab maintenance at 240 mg every 3 weeks or matched placebo was utilized in the JUPITER-02 trial. Those who received the toripalimab regimen achieved a median PFS of 11.7 months compared with 8.0 months among those who received chemotherapy alone (stratified HR, 0.52; 95% CI, 0.36-0.74; P = .0003). Investigators also reported that the median OS was not evaluable in either arm (stratified HR, 0.603).

“Nasopharyngeal carcinoma is an aggressive tumor that currently has no FDA-approved immuno-oncology treatment options, and we believe that toripalimab in combination with chemotherapy, if approved, will establish a new standard of care for first line treatment of advanced NPC,” Denny Lanfear, chief executive officer at Coherus, concluded. “Toripalimab is the PD-1 cornerstone of our immuno-oncology strategy, and we are pleased that the FDA has accepted the BLA for review. Including the toripalimab application, Coherus now has three product candidate BLAs under review by the FDA, and our team is making rapid progress toward our goal to diversify and expand our commercial product portfolio.”


1. Junshi Biosciences and Coherus announce FDA acceptance of BLA filing for toripalimab for treatment of nasopharyngeal carcinoma. News release. Junshi Biosciences. November 1, 2021. Accessed November 2, 2021. https://bit.ly/3CDYbjj
2. Xu R-H, Mai H-Q, Chen Q-Y, et al. JUPITER-02: the randomized, double-blind phase 3 study of toripalimab or placebo plus cisplatin and gemcitabine as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (NPC). J Clin Oncol. 2021;39(suppl 15):LBA2. doi:10.1200/JCO.2021.39.15_suppl.LBA2
3. Wang FH, Wei XL, Feng J, et al. Efficacy, safety, and correlative biomarkers of toripalimab in previously treated recurrent or metastatic nasopharyngeal carcinoma: a phase II clinical trial (POLARIS-02). J Clin Oncol. 2021;39(7):704-712. doi:10.1200/JCO.20.02712

2021-11-04T10:38:02-07:00November, 2021|Oral Cancer News|
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