Roy S. Herbst
Patients with previously treated, PD-L1-expressing advanced non-small cell lung cancer experienced long-term OS benefits with pembrolizumab compared with docetaxel, according to extended follow-up of the open-label, phase 2/phase 3 KEYNOTE-010 study presented at ESMO Immuno-Oncology Congress.
Results also showed long-term safety of the anti-PD-1 therapy among this patient population.
Previous results from KEYNOTE-010 — reported after a median follow-up of 13.1 months — showed 10 mg/kg or 2 mg/kg pembrolizumab (Keytruda, Merck) every 3 weeks improved OS over 75mg/m2 docetaxel among patients with previously treated advanced NSCLC and a PD-L1 tumor proportion score of at least 50% and at least 1%.
Roy S. Herbst, MD, PhD, ensign professor of medicine (medical oncology), professor of pharmacology and chief of medical oncology at Yale Cancer Center, presented updated results for patients who completed 35 cycles — or approximately 2 years — of pembrolizumab, and for patients who received a second course of pembrolizumab.
Because researchers observed no difference between the pembrolizumab doses in the study’s primary analysis, the present analysis pooled doses.
Median follow-up was 42.6 months (range, 35.2-53.2) for 1,033 patients.
Researchers observed improved OS with pembrolizumab vs. docetaxel in patients with a PD-L1 tumor proportion score of 50% or more (HR = 0.53; 95% CI, 0.42-0.66) and of 1% or more (HR = 0.53; 95% CI, 0.47-0.66;).
Among patients with PD-L1 tumor proportion score of 50% or more, pembrolizumab conferred a median OS of 16.9 months (95% CI, 12.3-21.4), compared with 8.2 months (95% CI, 6.4-9.8) among patients assigned docetaxel.
Thirty-five percent of patients achieved 36-month OS with pembrolizumab, compared with 13% assigned docetaxel.
Of 690 patients assigned pembrolizumab, 79 underwent 35 treatment cycles over approximately 2 years. Among those patients, 99% achieved 36-month OS, and 75 (95%) achieved partial or complete response.
A total of 72 patients (91%) survived, and 48 (64%) patients had an ongoing response. The median response duration was not reached (range, 4-46+ months).
Of the 79 patients, 32% had progressive disease following 35 cycles of pembrolizumab. Fourteen patients underwent a second course of pembrolizumab, and five completed 17 cycles. Six (43%) of the patients had partial response, five (36%) had stable disease and 11 (79%) survived.
Grade 3 to grade 5 treatment-related adverse events occurred in 16% of patients assigned pembrolizumab vs. 36% of patients assigned docetaxel, which appeared consistent with data from the primary analysis.
“At 43-month follow-up, pembrolizumab continued to prolong OS vs. docetaxel in patients with previously treated, PD-L1 expressing advanced NSCLC, with manageable long-term safety,” the researchers wrote. “Most patients who completed 35 cycles of pembrolizumab had durable response. The majority of patients with progressive disease by investigator review who received second-course pembrolizumab had either partial response or stable disease and remained alive.” – by Jennifer Byrne
Herbst RH, et al. Abstract LBA4. Presented at: ESMO Immuno-Oncology Conference; Dec. 13-16, 2018; Geneva.
Disclosures : Herbst reports consultant roles with Eli Lilly, Genentech/Roche, Merck, NextCare, Novartis and Pfizer, and research support from AstraZeneca, Eli Lilly and Merck. Please see the abstract for a list of all other authors’ relevant financial disclosures.