Lung cancer experts have been rejoicing over new longer-term results that continue to show the combination of immunotherapy and chemotherapy doubles survival compared with chemotherapy alone.
The results are from a 4-year follow-up of 160 patients with previously untreated stage IV nonsmall cell lung cancer (NSCLC) taking part in the KEYNOTE-189 trial of immunotherapy with pembrolizumab (Keytruda, Merck) plus pemetrexed–platinum chemotherapy versus chemotherapy plus placebo.
After a median follow-up of 46.3 months, the median overall survival (OS) in the intention-to-treat population was 22.0 months with the combination versus 10.6 months with chemotherapy alone (hazard ratio [HR], 0.60).
A similar pattern was seen for progression-free survival (PFS), with patients receiving the combination having a longer median PFS, at 9.0 months, versus 4.9 months with chemotherapy alone (HR, 0.50).
“Stellar data” exclaimed Riyaz Shah, MD, PhD, consultant medical oncologist, Maidstone and Tunbridge Wells NHS Trust, UK, on Twitter.
He described the results for the PD-L1 expression subgroups as “astonishing” and singled out the performance of the combination therapy in patients with very low (< 1%) tumor PD-L1 expression, showing more than 23% of patients were alive at 3 years versus just over 5% in the group given chemotherapy alone.
KN189 4y update. I don't know what to say. Stellar data. 31% alive at 36m! The PDL1 subgroup curves look astonishing with no crossing curves. Look at the PDL1<1% curve! 23.3% alive vs 5.3%. The HR gets smaller with lower PDL1! Excellent presentation by Grey et al #WCLC20 pic.twitter.com/dVFucDQb9T
— Dr Riyaz Shah (@DrRiyazShah) January 28, 2021
Charu Aggarwal, MD, MPH, Leslye M. Heisler associate professor for lung cancer excellence, Penn Medicine, Philadelphia, said the outcomes with the combination of chemotherapy and immunotherapy were “terrific.”
Terrific outcomes with combination chemoImmunotherapy in #NSCLC, 4 year update #WCLC20 #LCSM https://t.co/cTeBK9jxcZ
— Charu Aggarwal, MD, MPH (@CharuAggarwalMD) January 28, 2021
Sandip P. Patel, MD, medical oncologist, associate professor of medicine, UC San Diego Health, agreed that these long-term results were “very impressive.”
Very impressive long term results, the full effect of chemoIO hasn’t even fully been captured in our overall cancer mortality statistics in the US yet
— Sandip Patel MD (@PatelOncology) January 28, 2021
However, he noted the “full effect” of chemotherapy plus immunotherapy has not “fully been captured in our overall cancer mortality statistics in the US yet.”
The new results were presented January 28 at the 2020 World Conference on Lung Cancer, held virtually because of the ongoing pandemic.
Previous results from KEYNOTE-189 had already demonstrated that, after a median follow-up of 10.5 months, adding pembrolizumab to chemotherapy significantly improves both OS and PFS compared with chemotherapy alone.
The latest results show that the combination “continued to provide overall survival and progression-free survival benefit” in extended follow-up, said study presenter Jhanelle Elaine Gray, MD, chair, Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, Florida.
The 3-year OS rate with pembrolizumab plus chemotherapy compared with chemotherapy alone was 31.3% versus 17.4%, and estimated 3-year PFS was 11.8% versus 1.3%.
Crucially, substantial improvements were even seen in patients with tumors with a low level of PD-L1 expression (measured as the PD-L1 tumor proportion score [TPS]).
Gray highlighted the finding that the survival benefit with pembrolizumab plus chemotherapy was seen regardless of PD-L1 expression in the tumor, with a hazard ratio versus chemotherapy alone of 0.71 in patients with a TPS ≥ 50%, 0.66 in those with a TPS of 1%–49%, and 0.52 in patients with a TPS < 1%.
A similar pattern was seen with PFS, with a hazard ratio of 0.36 in patients with a TPS ≥ 50%, 0.54 in those with a TPS of 1%–49%, and 0.68 in patients with a TPS < 1%.
In addition, overall response rate and duration of response were also improved with combination therapy, regardless of tumor PD-L1 expression.
Among 56 patients who completed 35 cycles of pembrolizumab, the objective response rate was 87.5% (with 10.7% having a complete response and 76.8% a partial response).
At the data cutoff, 45 patients were alive, 28 did not have progressive disease, and seven had started a second course of pembrolizumab.
The side effect profile of the combination was “manageable,” Gray reported.
The combination arm was associated with more grade 3-5 treatment-related adverse events than the chemotherapy alone arm, at 52.1% versus 42.1%, and more grade 3-5 immune-related adverse events and infusion reactions, at 27.7% versus 13.4%.
Events leading to treatment discontinuation were also more common with pembrolizumab plus chemotherapy than chemotherapy, at 27.4% versus 9.9%.
The combination of pembrolizumab plus pemetrexed–platinum has already become “a standard-of-care-therapy for patients with newly diagnosed metastatic nonsquamous NSCLC,” Gray commented.
The study was funded by MSD. Gray has reported receiving grant support and/or honoraria from Array, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Merck, and institutional funding from MSD.
2020 World Conference on Lung Cancer Singapore. Abstract FP13.02. Presented January 28, 2021.
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