ESMO Immuno-Oncology 2018: KEYNOTE-010: Long-Term Treatment With Pembrolizumab in Previously Treated NSCLC
Patients with previously treated, advanced non–small cell lung cancer (NSCLC) who received pembrolizumab (Keytruda) showed significantly longer overall survival (OS) compared to those treated with docetaxel, Herbst et al reported at the ESMO Immuno-Oncology Congress 2018 in Geneva, Switzerland (Abstract LBA4).
Roy S. Herbst, MD, PhD, of Yale University School of Medicine, presented long-term findings from the global, open-label, phase II/III KEYNOTE-010 trial.
KEYNOTE-010 enrolled adult patients with previously treated advanced NSCLC and programmed cell death-ligand 1 (PD-L1) tumor proportion scores (TPS) ≥ 1%. Patients were randomly assigned 1:1:1 to receive pembrolizumab at 10 mg/kg or 2 mg/kg every 3 weeks for up to 35 cycles, or to docetaxel at 75 mg/m2 every 3 weeks for the maximum number of cycles allowed per local guidelines, until disease progression or intolerable toxicity. Response assessments per RECIST v1.1 were made every 9 weeks by independent central review, and survival was evaluated every 2 months post-treatment. No difference between pembrolizumab doses was demonstrated in the primary analysis, thus doses were pooled in this analysis.
Previously reported results from this trial showed OS was improved with pembrolizumab over docetaxel in subgroups of patients with high and low PD-L1 expression levels, defined as PD-L1 TPS ≥ 50% and ≥ 1% with median follow-up of 13.1 months.
At the Immuno-Oncology Congress, Dr. Herbst reported updated OS and safety results with 43 months median follow-up in the study overall, and long-term results for patients who had completed 35 cycles of pembrolizumab, and for patients who received a second course of pembrolizumab therapy.
Findings
After median follow-up of 42.6 months (range = 35.2–53.2 months), OS in the overall population of 1,033 patients was improved with pembrolizumab over docetaxel.
Patients with PD-L1 TPS ≥ 50% demonstrated significantly improved OS with pembrolizumab compared to docetaxel. Median OS was 16.9 (95% confidence interval [CI] = 12.3–21.4) months with pembrolizumab vs 8.2 (95% CI = 6.4–9.8) months with docetaxel (hazard ratio [HR] = 0.53; 95% CI = 0.42–0.66; P < .00001). In this cohort, the 36-month OS rates were 35% vs 13%, respectively.
Similarly, OS was improved with pembrolizumab vs docetaxel in patients with TPS ≥ 1% (HR= 0.69; 95% CI = 0.60–0.80; P < .00001).
Thirty-five cycles or 2 years of pembrolizumab were delivered to 79 of 690 patients. Among these patients, the 36-month OS rate was 99%. Ninety-five percent of these patients achieved complete or partial response as the best response, and 48 (64%) had an ongoing response. The median duration of response was not reached (range = 4–46+ months).
Among patients who completed 35 cycles or 2 years of pembrolizumab, 72 (91%) patients remained alive. Progressive disease was observed in 25 (32%) patients, per investigator. A second course of pembrolizumab was delivered to 14 patients, of whom 5 patients completed 17 cycles. In this group, 11 (79%) patients remained alive, with 6 (43%) patients achieving partial response, and 5 (36%) patients showing stable disease.
The safety profile was similar to that reported for the primary analysis. Grade 3–5 treatment-related adverse events occurred in 16% of pembrolizumab-treated patients overall, compared to 37% of docetaxel patients.
Researchers concluded, “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.”
Disclosure: Funding for the study was provided by Merck Sharp & Dohme. The study authors’ full disclosures can be found at academic.oup.com.
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