Pembrolizumab regimen confers substantial survival benefit in untreated metastatic nonsquamous NSCLC
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First-line pembrolizumab in combination with pemetrexed and platinum-based chemotherapy substantially extended PFS and OS among patients with metastatic nonsquamous non-small cell lung cancer, according to an updated analysis of the randomized phase 3 KEYNOTE-189 study published in Journal of Clinical Oncology.
Researchers observed the survival benefit regardless of PD-L1 expression, liver metastases or brain metastases. The regimen also appeared safe.
“This regimen became the standard of care in 2017 after its approval and has resulted in a 16% improvement in 2-year survival,” Shirish M. Gadgeel, MD, Mary Lou Kennedy research professor in thoracic oncology, co-leader of thoracic oncology research program and professor in the division of hematology and oncology in the department of internal medicine at University of Michigan, told Healio. “The prognosis, however, is still limited because this is not considered curative treatment.”
Before immunotherapy, platinum-based chemotherapy served as first-line treatment for patients with advanced nonsquamous NSCLC and no EGFR or ALK alterations. Select patients had the option of also receiving bevacizumab.
Results of the KEYNOTE-189 study showed pembrolizumab (Keytruda, Merck), an anti-PD-1 monoclonal antibody, improved survival outcomes when combined with pemetrexed and platinum chemotherapy as first-line treatment of advanced nonsquamous NSCLC.
Gadgeel and colleagues reported findings from an updated analysis of the study, in which researchers randomly assigned 616 patients to pemetrexed-platinum chemotherapy with pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for four cycles, followed by pemetrexed maintenance plus pembrolizumab or placebo for up to 35 cycles. Eligible patients in the placebo group who experienced disease progression could switch to pembrolizumab monotherapy.
The pembrolizumab and placebo combination groups had similar baseline characteristics, including median age (65 years vs. 63.5 years). Similar percentages of patients in each group had PD-L1 tumor proportion scores of less than 1% (31% vs. 30.6%), 1% to 49% (31.2% vs. 28.2%), or 50% or greater (32.2% vs. 34%).
Median follow-up was 23.1 months.
Patients in the pembrolizumab group achieved longer median OS (22 months vs. 10.7 months; HR = 0.56;95% CI, 0.45-0.7) and longer median PFS (9 months vs. 4.9 months; HR = 0.48; 95% CI, 0.4-0.58).
The investigators also reported longer median time from randomization to objective tumor progression on next-line treatment or death of any cause, whichever occurred first, in the pembrolizumab group (17 months vs. 9 months; HR = 0.49; 95% CI, 0.4-0.59).
Researchers observed the PFS and OS benefits with pembrolizumab regardless of PD-L1 expression or the presence of liver or brain metastases.
The groups had similar incidence of grade 3 to grade 5 adverse events.
“These results support pembrolizumab plus pemetrexed-platinum as a standard-of-care rst-line therapy among patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK alterations, regardless of tumor PD-L1 expression,” Gadgeel and colleagues wrote. – by John DeRosier
For more information:
Shirish M. Gadgeel, MD, can be reached at Northville Health Center, Floor 2, 39901 Traditions Drive, Northville, MI 48168-9493; email: sgadgeel@med.umich.edu.
Disclosures: Gadgeel reports consultant/advisory roles with and honoraria from AstraZeneca, Genentech and Merck; consultant/advisory roles with Boehringer Ingelheim, Bristol-Myers Squibb, Novocure, Takeda and Xcovery; travel expenses from AstraZeneca; and research funding to his institution from Aeglea Biotherapeutics, Astellas, Blueprint Medicines, Daiichi Sankyo, Genentech, G1 Therapeutics, Merck and Pfizer. Please see the study for all other authors’ relevant financial disclosures.
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