Summary
With longer follow-up, pembrolizumab plus chemotherapy continued to improve efficacy outcomes in previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC) over placebo and chemotherapy, with a manageable toxicity profile, according to findings presented at the ASCO 2020 Annual Meeting (Abstract 9582).
“The randomized, double-blind, phase III KEYNOTE-189 study compared pembrolizumab plus pemetrexed-platinum to placebo plus pemetrexed-platinum as a first-line therapy in patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations, regardless of PD-L1 expression,” noted study author Delvys Rodriguez-Abreu, MD, from the Universidad de Las Palmas de Gran Canaria.
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Original Article
Pembrolizumab + Chemo Continues to Improve Efficacy in Metastatic Nonsquamous NSCLC
Oncology Times
By Catlin Nalley
With longer follow-up, pembrolizumab plus chemotherapy continued to improve efficacy outcomes in previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC) over placebo and chemotherapy, with a manageable toxicity profile, according to findings presented at the ASCO 2020 Annual Meeting (Abstract 9582).
“The randomized, double-blind, phase III KEYNOTE-189 study compared pembrolizumab plus pemetrexed-platinum to placebo plus pemetrexed-platinum as a first-line therapy in patients with metastatic nonsquamous NSCLC without sensitizing EGFR or ALK mutations, regardless of PD-L1 expression,” noted study author Delvys Rodriguez-Abreu, MD, from the Universidad de Las Palmas de Gran Canaria.
“After a median follow-up of 10.5 months, patients in the pembrolizumab arm had improved OS and PFS compared to those in the placebo arm,” he said, during his presentation. “We report findings from the protocol-specified final analysis.”
Key Details
Patients enrolled in KEYNOTE-189 were randomized to receive 35 cycles of pembrolizumab 200 mg Q3W (n=410) or placebo Q3W (n=206) plus 4 cycles of pemetrexed and carboplatin/cisplatin followed by maintenance pemetrexed.
Primary endpoints included PFS and OS; the secondary endpoint was ORR. An exploratory endpoint was PFS2 (time from randomization to objective tumor progression on next-line treatment/death).
“At data cutoff, the median time from randomization was 31 months,” noted Rodriguez-Abreu. “Seventeen patients in the pembrolizumab plus pemetrexed-platinum arm were still receiving study treatment compared to just one in the placebo group. Eighty-four patients in the placebo arm crossed over to pembrolizumab.
“Among patients in the pembrolizumab plus pemetrexed-platinum arm, the median OS was more than twice that of patients in the placebo arm (22.0 months vs. 10.6 months; HR, 0.56),” he reported. “The OS rates at 12 and 24 months were substantially higher in patients in the pembrolizumab plus pemetrexed-platinum arm compared with those in the placebo plus pemetrexed-platinum arm.”
The combination of pembrolizumab plus pemetrexed-platinum improved OS across all PD-L1 subgroups compared to those in the placebo arm, including PD-L1 negative patients, according to Rodriguez-Abreu.
“Median PFS was 9 months in the pembrolizumab arm compared with 4.9 months in the placebo arm, with a hazard ratio of 0.49,” he said. “PFS rates at 12 and 24 months were substantially higher in patients in the pembrolizumab arm compared to those in the placebo arm.”
The researchers reported that PFS2 was improved in the pembrolizumab combination compared to the placebo group. Median PFS2 was 17 months in the pembrolizumab plus pemetrexed-platinum arm versus 9 months among patients who received placebo.
“Fifty-six patients completed 35 cycles, approximately 2 years, of treatment with pembrolizumab,” Rodriguez-Abreu noted. “Among these patients, the ORR was 85.7 percent with four complete responses and 44 partial responses. The remaining eight patients had stable disease. Median OS in these patients was not reached.”
In terms of safety, 72.1 percent of patients in the pembrolizumab plus pemetrexed-platinum arm had grade 3-5 adverse events compared with 66.8 percent in placebo. There was a higher proportion of immune-mediated adverse events and infusion reactions among patients in the pembrolizumab plus pemetrexed-platinum group (27.2% vs. 12.9%, any grade).
In summary, patients with metastatic nonsquamous NCSLC and no prior systemic treatment who were treated with pembrolizumab plus pemetrexed-platinum continued to show improved outcomes in OS, PFS, and ORR compared to those who received placebo plus pemetrexed-platinum, according to Rodriguez-Abreu.
“PFS2 results indicate the benefits of pembrolizumab plus pemetrexed-platinum even through the next line of therapy,” he noted. “Pembrolizumab in combination with pemetrexed-platinum is today a standard-of-care therapy for patients with newly diagnosed metastatic, nonsquamous NSCLC.
“We not only want our patients to live longer,” Rodriguez-Abreu told Oncology Times. “We want them to live longer with less toxicities and a good quality of life. We need to continue conducting research, because we have a gap to complete, but I'm sure that the KEYNOTE-189 will change the way we treat lung cancer.”
Catlin Nalley is a contributing writer.