The addition of pembrolizumab (Keytruda) to a standard platinum doublet as first-line therapy improved overall and progression-free survival in patients with metastatic squamous non–small cell lung cancer (NSCLC), in the primary analysis of KEYNOTE-407.1,2 Furthermore, it did not seem to matter which taxane was combined with pembrolizumab: paclitaxel or nanoparticle albumin-bound (nab)-paclitaxel (Abraxane).
In the primary analysis, at a median follow-up of 7.8 months, the median overall survival was 15.9 months in patients who received pembrolizumab plus carboplatin/paclitaxel or nab-paclitaxel vs 11.3 months in those treated with standard chemotherapy plus placebo (P < .001). The median progression-free survival was significantly better in the pembrolizumab arm: 6.4 months vs 4.8 months for the placebo group (P < .001). Progression-free survival was also better in all prespecified subgroups, including based on type of chemotherapy and programmed cell death ligand 1 (PD-L1) levels of expression.
At the International Association for the Study of Lung Cancer (IASLC) 19th World Conference on Lung Cancer in Toronto, an exploratory analysis regarding the impact of the taxanes used in -KEYNOTE-407 on efficacy and adverse events was presented,1,2 and the results of the overall analysis of the trial were published simultaneously in TheNew England Journal of Medicine.3
Balazs Halmos, MD
“We saw consistent benefits with pembrolizumab regardless of which taxane was used. It doesn’t seem to make a difference. Regimens with both taxanes had similar efficacy and were tolerable. This is a practice-changing study [with regard to the addition of pembrolizumab],” said lead author Balazs Halmos, MD, of the Montefiore Medical Center, Albert Einstein College of Medicine, New York.
“Results of this and other trials suggest that pembrolizumab has a role in first-line treatment of squamous NSCLC regardless of histologic subtype or PD-L1 tumor proportion score,” wrote the authors of the article published in TheNew England Journal of Medicine.3
KEYNOTE-407 was a double-blind, multicenter phase III study that randomly assigned 559 patients with metastatic squamous -NSCLC in a 1:1 ratio to receive either pembrolizumab (up to 35 cycles) plus carboplatin/paclitaxel or carboplatin/nab-paclitaxel for 4 cycles (investigator’s choice) or the same chemotherapy plus placebo. Patients with all levels of PD-L1 expression were included.
Patients were stratified by PD-L1 level (≥ 1% vs < 1%), choice of taxane (paclitaxel vs nab-paclitaxel), and geographic region (East Asia vs the rest of the world). Those who received paclitaxel (but not nab-paclitaxel) were pretreated with glucocorticoids and antihistamines. Treatment was continued until radiographic disease progression, unacceptable toxicity, investigator’s decision, or withdrawal of patient consent.
Survival data favored pembrolizumab at all levels of PD-L1 expression. Overall survival was improved by 39% in patients with no detectable PD-L1 (ie, < 1%); by 35% in those with ≥ 1% PD-L1; by 43% at 1% to 49% PD-L1; and by 36% with PD-L1 ≥ 50%.
In the overall trial, adverse events were similar between the two treatment arms. Adverse events of any grade were reported in 98.2% of the pembrolizumab group and 97.9% of the placebo group. The most common grade 3 or 4 adverse events were anemia (15.5% with pembrolizumab vs 20.4% with placebo), neutropenia (22.7% vs 24.6%), and thrombocytopenia (6.8% vs 6.4%). Immune-related adverse events and infusion reactions were more frequent with pembrolizumab (28.8% vs 8.6% for placebo).
Paclitaxel vs Nab-Paclitaxel
“Overall survival improved significantly with the addition of pembrolizumab irrespective of which taxane was used, but numerical results were somewhat better in the nab-paclitaxel groups in both arms of the study,” Dr. Halmos said. Among pembrolizu-mab-treated patients, the median overall survival was 14 months with paclitaxel vs not yet reached for those who received nab-paclitaxel.
Among pembrolizumab-treated patients, the median progression-free survival was 6.4 months for those treated with paclitaxel and 6.5 months for those who received nab-paclitaxel. Objective response rates were similar with paclitaxel and nab-paclitaxel in pembrolizu-mab-treated patients (57.4% vs 58.7%). The rate of more than one adverse event of any grade in pembrolizumab-treated patients was 97.6% in the paclitaxel cohort vs 88.1% in the nab-paclitaxel cohort. However, grade 3 and higher adverse events were less frequent with paclitaxel (63.9% vs 78.9%).
“Fewer patients were able to get all the doses of nab-paclitaxel,” noted Dr. Halmos. “Almost all patients received corticosteroids with paclitaxel, and 90% received corticosteroids during cycles 1 and 4 with nab-paclitaxel.” ■
DISCLOSURE: The study was funded by Merck Sharpe & Dohme. Dr. Halmos reported receiving consulting fees and clinical research funds from Merck, BMS, AstraZeneca, Boehringer-Ingelheim, Genentech, Novartis, Pfizer, Takeda, Spectrum, Ignyta, Eli-Lilly, Foundation Medicine, and Guardant Health.
1. Paz-Ares LG, et al: Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel with or without pembrolizumab for patients with metastatic squamous non-small cell lung cancer. 2018 ASCO Annual Meeting. Abstract 105. Presented June 3, 2018.
2. Halmos B, et al: Choice of taxane and outcomes in the KEYNOTE-407 study of pembrolizumab plus chemotherapy for metastatic squamous NSCLC. 2018 World Conference on Lung Cancer. Abstract MA10.08. Presented September 25, 2018.
Antoinette Wozniak, MD
Formal discussant Antoinette Wozniak, MD, of UPMC Hillman Cancer Center, Pittsburgh, said, “KEYNOTE-407 is a very positive trial, showing improved overall and progression-free survival with the addition of pembrolizumab (Keytruda) to standard chemotherapy.” In her...!-->!-->