ASCO: Pemetrexed Plus Carboplatin No Better Than Bevacizumab-Containing Regimen in NSCLC

CHICAGO-A phase III study comparing pemetrexed and carboplatin with paclitaxel, carboplatin, and bevacizumab failed to find a difference in a composite endpoint of progression-free survival and severe drug-related toxicities in patients with nonsquamous non–small-cell lung cancer (NSCLC), according to results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

“Pemetrexed plus carboplatin and paclitaxel, carboplatin, and bevacizumab are efficacious regimens. [But] these two combination regimens have not been directly compared,” said Ralph Zinner, MD, of MD Anderson Cancer in Houston, who presented the results. His group hypothesized that toxicity may be reduced with the pemetrexed combination, and thus designed a trial with an endpoint dubbed G4PFS-progression-free survival along with a lack of grade 4 toxicities. In other words, the endpoint was reached with disease progression or death, or with the occurrence of any grade 4 adverse event.

The pemetrexed arm of the study had 182 patients, while the bevacizumab arm had 179; 98 in the first group went on as planned to receive maintenance pemetrexed and 95 in the latter group received maintenance bevacizumab.

The median G4PFS in the pemetrexed patients was 3.9 months, vs 2.9 months in the bevacizumab group, for a hazard ratio of 0.85 (95% CI, 0.70–1.04; P = .176). PFS alone was also no different between the groups, at 4.4 months and 5.5 months in the two groups (P = .610). The response rate was 23.6% with pemetrexed and 27.4% with the bevacizumab-containing regimen (P = .414). Overall survival was 10.5 months and 11.7 months, respectively, which again was not a significant difference (P = .615).

There were, however, some differences in toxicity between the two groups. There was a higher incidence of grade 3 or 4 anemia and thrombocytopenia in the pemetrexed group (P < .001 for both), while neutropenia was more common with the bevacizumab-containing regimen (P < .001). Alopecia and sensory neuropathy were more common in the bevacizumab, though not for grade 3 or worse neuropathy.

“The primary objective was not met,” Dr. Zinner said. “The PFS and OS results for the two-drug and three-drug regimens were similar, and there were no unexpected toxicities.”

Luis Paz-Ares, MD, PhD, of the Hospital Universitario Virgen del Rocio in Sevilla, Spain, commented on the study and said this may not be the ideal endpoint to compare the two regimens. To compare hard survival endpoints, however, more than 1,000 patients would likely be necessary. “Are those regimens equal? We don’t know at the present time, but we may say that they are probably not that different… in terms of efficacy,” he said.