We have seen fascinating interim results, and we wait for their validation.
—Martin Reck, MD, PhD
Martin Reck, MD, PhD, Head of Thoracic Oncology at the Hospital Grosshansdorf in Germany, discussed the anti–PD-1 abstracts at the ASCO Annual Meeting.
“We have seen tremendous results for immunotherapies for the reactivation of the immune system in patients with advanced melanoma. The question is, is this also true for patients with lung cancer?” he asked.
Commenting on pembrolizumab, he noted that the efficacy seems not dependent on histology of the tumors, though better response rates are seen in patients with PD-L1 expression. “We see a signal of better responses in these tumors; however, we have to be very cautious because there have been substantial differences with regard to the antibody used for assessment, the scoring system, the quality of the sample used for assessment, and so forth,” he noted.
Regarding the nivolumab studies, he suggested that the combination of this drug with erlotinib “requires more validation and translational science,” especially with regard to its activity against T790M-mutant patients.
“There is little knowledge about the correlation of the T790M mutation and checkpoint inhibition,” he noted. “It’s of interest, as well, to see the effect of this combination in EGFR mutation–positive, T790M mutation–negative patients who are refractory to an EGFR tyrosine kinase inhibitor. The data have to be put into perspective of the third-generation tyrosine kinase inhibitors,” which are more efficacious in the T790M-mutant population.
For nivolumab plus ipilimumab, efficacy seems unrelated to differences in dosing and schedule, or to PD-L1 expression, but toxicity is fairly high, he said. “I think the 10-mg/kg dose may be too toxic for this combination, and especially we need to keep our eye on pulmonary toxicity,” he said.
As monotherapy, nivolumab is better tolerated. “Severe adverse events were seen in 20%, and so far we have not seen any severe pulmonary toxicity,” he pointed out.
A median progression-free survival of 9 months and 1-year overall survival rate of 75% is impressive, he commented. In PD-L1–positive patients, median progression-free survival was 46 weeks, with 80% of patients alive at 1 year. PD-L1–negative patients did not respond.
“Of interest, in PD-L1–negative patients, even without any responses, had a median progression-free survival of 36 weeks, and 1-year survival was 71%, but we have to remember we are talking about only seven patients,” he cautioned.
Whether the anti-PD-1 agents are truly superior to the best chemotherapy and targeted agents in NSCLC will only be answered by randomized trials, he said, “but we have seen fascinating interim results, and we wait for their validation.” ■
Disclosure: Dr. Reck reported no potential conflicts of interest.
Monoclonal antibodies targeting the programmed death receptor-1 (PD-1) pathway are expected to answer an unmet need in non–small cell lung cancer (NSCLC). With first-line platinum-doublets, 1-year overall survival is 30% to 50%, and while treatments targeting sensitizing mutations are more...