Positive Early Data Support Use of Pembrolizumab in Advanced Non-Small Cell Lung Cancer

Four-year follow-up data from cohort G KEYNOTE-021 reinforced the use of the immune checkpoint inhibitor pembrolizumab (Keytruda) in patients with advanced non–small cell lung cancer (NSCLC), Merck announced in a press release.

These new data include findings from cohort G of the phase 1/2 KEYNOTE-021 study (NCT02039674) of pembrolizumab plus chemotherapy, which were presented during the International Association for the Study of Lung Cancer 2020 North America Conference on Lung Cancer.

Positive findings from cohort G of the KEYNOTE-021 study demonstrated frontline treatment with pembrolizumab in combination with chemotherapy induced a significant improvement in objective response rates (ORRs), progression-free survival (PFS), and a sustained long-term survival benefit as treatment of patients with advanced nonsquamous NSCLC, compared with chemotherapy alone. Cohort G included patients without EGFR or ALK genomic tumor aberrations.

“Over the last 5 years, pembrolizumab has become foundational in the treatment of metastatic lung cancer. The long-term data from KEYNOTE-021 (Cohort G) reinforce the use of pembrolizumab in combination with chemotherapy in certain advanced lung cancer patients, while data from our oncology pipeline reflect our commitment to exploring a number of new combinations with pembrolizumab that we believe could have a meaningful impact for more lung cancer patients,” said Vicki Goodman, MD, vice president, oncology clinical research, Merck Research Laboratories, in a statement.

The ORR in KEYNOTE-021 was 58% with the pembrolizumab regimen versus 33% with chemotherapy alone, and the risk of disease progression or death was reduced by 46% (HR, 0.54; 95% CI, 0.35-0.83) with pembrolizumab.

Among patients who received pembrolizumab in combination with pemetrexed and platinum chemotherapy, 50% remained alive at 3 years compared with 37% among those who received pemetrexed and platinum chemotherapy alone. The combination regimen also reduced the risk of death by 29% (HR, 0.71; 95% CI, 0.45-1.12) compared with chemotherapy alone.

The median overall survival (OS) was 34.5 months with the combination versus 21.1 months with chemotherapy alone, and the OS benefit was seen despite a 70% effective crossover rate from chemotherapy to anti-PD-1/PD-L1 therapy, which included 28 patients who were treated with the combination regimen as part of the on-study crossover.

The median PFS was 24.5 months with the combination (range, 9.7-36.3) versus 9.9 months (range, 6.2-15.2). The estimated 3-year PFS rate was 37% with the combination and 16% with chemotherapy alone.

The median duration of response (DOR) was 1 year longer with the combination at 36.3 months (range, 1.4+ to 49.3+) versus 22.8 months with chemotherapy alone (range, 2.8+ to 47.2+). In addition, 51% of patients in the pembrolizumab arm had responses that lasted at least 3 years compared with 47% in the control arm.

At 3 years, 92% of patients who had completed 2 years of treatment with pembrolizumab remained alive, occurring in 11 out of 12 patients. All 12 patients were able to achieve an objective response, and the estimated 3-year DOR rate was 100%, while the median DOR was not reached (range, 11.7+ to 49.3+).

The study did not demonstrate any new safety signals for pembrolizumab in combination with the chemotherapy regimen, and among those were treated, 39% from the pembrolizumab arm and 31% from the chemotherapy arm experienced grade 3-5 treatment-related adverse events (TRAEs), and these led to discontinuations in 17% and 16%, respectively. Grade 3-5 TRAEs led to death in 2% of the pembrolizumab arm and 3% in the chemotherapy alone arm.

These findings from KEYNOTE-021 represent the longest follow-up data for the combination of an anti-PD-1/PD-L1 therapy with chemotherapy in the frontline setting of NSCLC. The findings from the study of quavonlimab with pembrolizumab also demonstrated promising findings with anti-tumor activity and an acceptable safety profile as treatment of patients with advanced NSCLC.

_Reference

_{1. Merck presented three-year survival data for Keytruda (pembrolizumab) in combination with chemotherapy and updated phase 1/2 data for investigational quavonlimab (mk-1308) in combination with Keytruda in advanced non-small cell lung cancer. News Release. Merck. October 16, 2020. Accessed October 19, 2020. https://bit.ly/2T5MDjF​}

_{2. Awad MM, Gadgeel SM, Borghaei H, et al. KEYNOTE-021 cohort g long-term follow-up: first-line pemetrexed and carboplatin with or without pembrolizumab for advanced nonsquamous NSCLC. Presented at the IASLC 2020 North America Conference on Lung Cancer Worldwide Virtual Event (NACLC 2020); October 16–17, 2020. Abstract: OFP01.02.}