Author: Michael Smith, North American Correspondent, MedPage Today
A novel non-platinum-based regimen was efficacious in recurrent or metastatic squamous cell head and neck cancer, researchers said. The combination of pemetrexed (Alimta) and bevacizumab (Avastin) yielded a response rate of 30% in a small single-arm trial, according to Athanassios Argiris, MD, of the University of Pittsburgh, and colleagues.
The combination also increased the length of time before patients progressed, and increased median overall survival, Argiris and colleagues reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology here.
Patients with recurrent or metastatic disease typically have a poor prognosis, the researchers said, with median survival between six and nine months with standard chemotherapy. But, in other research, adding the monoclonal antibody cetuximab (Erbitux) to platinum-based chemotherapy increased survival, they said.
Bevacizumab is a monoclonal antibody that targets the vascular epithelial growth factor (VEGF), which is expressed in squamous cell head and neck cancer; high levels of VEGF correlate with poor outcome, they noted.
The researchers hypothesized that the antibody might enhance the activity of pemetrexed, which is a multi-targeted antifolate indicated for malignant pleural mesothelioma and non-small cell lung cancer.
To test the idea, they analyzed results of treating 37 patients given 500 mg/m2 of pemetrexed and 15 mg/kg of bevacizumab intravenously every 21 days until disease progression. Patients were also given folic acid and vitamin B12.
The primary endpoint of the study was time to progression, they said, but the researchers also isolated DNA from 28 patients to see if genetic variations played a role in survival.
- Two patients had a complete response and 11 had a partial response, for a response rate of 30%. As well, 21 patients had stable disease for a disease control rate of 86%.
- The median time to progression was 4.9 months.
- Median overall survival was 11.5 months.
- Bleeding events of grade two or greater occurred in six patients, including four that were grade three and two that were fatal.
The researchers said that it is difficult to know whether the bleeding was associated with the drugs or was part of the natural history of the disease.
The DNA analysis showed that a single nucleotide polymorphism (SNP) in the gene for methylenetetrahydrofolate reductase was associated with significantly worse overall survival, although no other tested variants had significant associations.
Patients with two copies of the A variant in the MTHFR A1298C polymorphism had a median overall survival of 4.2 months, compared with 32.8 months for those with other variants. The difference was significant at P=0.006, the researchers said.
The “data are favorable” compared with other non-platinum regimens, according to Ranee Mehra, MD, of Fox Chase Cancer Center in Philadelphia, who was not involved in the research but who discussed it in an oral session. But she noted that the impact of second-line therapy on overall survival remains unclear, especially since some patients may have gone on to platinum-based regimens, which might have affected their outcomes.
That said, she added, “bevacizumab is a novel agent in squamous cell head and neck cancer that has a favorable response rate.”
Larger – and randomized — trials are needed to define the extent of any benefit, she said, adding that one such trial – Eastern Cooperative Oncology Group 13056 – is currently underway.
1. Journal of Clinical Oncology
2. Argiris A et al. “Pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results and correlation with TS, MTHFR, and VEGF gene polymorphisms.” J Clin Oncol 28:7s, 2010 (suppl; abstr 5533)