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Pembrolizumab doubles median OS for metastatic NSCLC

Issue: December 10, 2017

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Julie Brahmer

First-line pembrolizumab induced significantly longer median OS than chemotherapy among patients with metastatic non-small cell lung cancer and high PD-L1 expression, according to long-term follow-up of KEYNOTE-024 presented at International Association for the Study of Lung Cancer World Conference on Lung Cancer.

The significant benefit observed with pembrolizumab (Keytruda, Merck) persisted at this 2-year analysis despite patient crossover from the control arm.

“As we continue to see updated findings from this study of patients with NSCLC in the first-line setting, practitioners are gaining valuable insights into the longer-term clinical benefit of Keytruda,” Martin Reck, MD, PhD, head of the department of thoracic oncology at LungenClinic in Grosshansdorf, Germany, said in a Merck-issued press release. “The significant OS findings observed in KEYNOTE-024, which includes patients who have a poor prognosis, reinforce the use of Keytruda in appropriate patients in the first-line treatment of this disease.”

Earlier findings from KEYNOTE-024, presented last year at the European Society for Medical Congress after a median follow-up of 11.2 months, showed a significant PFS benefit with pembrolizumab vs. platinum-based chemotherapy (HR = 0.5; 95% CI, 0.37-0.68). However, median OS had not been reached in the pembrolizumab arm at the time of that analysis.

Julie R. Brahmer, MD, MSc, director of the thoracic oncology program and associate professor of oncology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medicine, presented updated findings conducted after a median follow-up of 25.2 months.

The analysis included 305 patients with a PD-L1 tumor proportion score of at least 50% randomly assigned to received 35 cycles of 200 mg pembrolizumab every 3 weeks (n = 154; median age, 64.5 years; 59.7% men) or investigator’s choice of carboplatin/cisplatin plus gemcitabine, carboplatin plus paclitaxel, or carboplatin/cisplatin plus pemetrexed with optional pemetrexed maintenance (n = 151; median age, 66 years; 62.9% men).

Patients in the chemotherapy arm who experienced disease progression could cross over to the pembrolizumab arm.

PFS served as the study’s primary endpoint. OS, overall response rate and safety served as secondary endpoints.

At the July 10, 2017, data cutoff, 73 patients (47.4%) in the pembrolizumab arm and 96 patients (63.3%) in the chemotherapy arm had died.

Twenty-three patients in the pembrolizumab arm remained on treatment compared with two patients in the chemotherapy arm, both of whom received pemetrexed maintenance.

Seventeen patients in the pembrolizumab arm and 27 in the chemotherapy arm completed treatment.

Eighty-two patients (median age, 65 years; 57.3% men) assigned chemotherapy met criteria to cross over to the pembrolizumab arm, and an additional 12 patients received an anti-PD-1 therapy outside of the study for a 63% crossover rate.

Median OS was 30 months (95% CI, 18.3-not reached) in the pembrolizumab arm — a “remarkable” result, Brahmer said — and 14.2 months (95% CI, 9.8-19) in the chemotherapy arm (HR for OS = 0.63; 95% CI, 0.47-86).

More patients assigned pembrolizumab achieved 12-month OS (70.3% vs. 54.8%) and an objective response (45.5% vs. 29.8%). Researchers reported an ORR in the crossover population of 20.7%.

Median duration of response has not yet been reached (95% CI, 1.8+ to 20.6+) for patients assigned pembrolizumab, 7.1 months (95% CI, 2.1+ to 18.1+) for those assigned chemotherapy, and not reached (95% CI, 2.1+ to 22.9+) for the crossover population.

Fewer patients assigned pembrolizumab experienced any-grade adverse events (76.6% vs. 90%) and grade 3 to grade 5 events (31.2% vs. 53.3%). In the crossover population, 61% of patients experienced adverse events, and 9.8% of patients experienced grade 3 to grade 4 events.

Treatment-related adverse events led to two deaths in the pembrolizumab arm and three deaths in the chemotherapy arm.

“Pembrolizumab remains a standard of care for first-line therapy for patients with NSCLC expressing PD-L1 tumor proportion score of at least 50%,” Brahmer said during her presentation. – by Alexandra Todak

Reference:

Brahmer JR, et al. Abstract OA 17.06. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer; Oct. 15-18, 2017; Yokohama, Japan.

Disclosures: Brahmer reports consultant/advisory roles with Bristol-Myers Squibb, Celgene, Janssen Oncology, Lilly, Merck and Syndax; and research funding or travel accommodations from AstraZeneca, Bristol-Myers Squibb, Five Prime Therapeutics, Incyte, Janssen Oncology and Merck. Please see the abstract for a list of all author’s relevant financial disclosures.