In mNSCLC with no EGFR or ALK genomic tumor aberrations and PD-L1 ≥50%
- Median OS: 30 months (95% CI, 18.3–NR) with KEYTRUDA vs 14.2 months (95% CI, 9.8–19.0) with chemotherapyd
- Events observed: 29% (44/154) with KEYTRUDA and 42% (64/151) with chemotherapy
UPDATED OVERALL SURVIVAL DATA
LIMITATION: The post-hoc analysis based on extended follow-up in KEYNOTE-024 was exploratory in nature. No formal statistical testing was planned and, therefore, no statistical conclusions can be drawn.
- Median OS: 26.3 months with KEYTRUDA (95% CI, 18.3–40.4) vs 14.2 months (95% CI, 9.8–18.3) with chemotherapy.
- Events observed: 63% (97/154) with KEYTRUDA and 75% (113/151) with chemotherapy.
APPROPRIATE PATIENTS
Risk of disease progression reduced by half
- HR=0.50; 95% CI, 0.37–0.68; P<0.001b
- 10.3-month median PFS (95% CI, 6.7–NR) with KEYTRUDA vs 6.0 months (95% CI, 4.2–6.2) with chemotherapy
- Events observed: 47% (73/154) with KEYTRUDA and 77% (116/151) with chemotherapy
Nearly half of patients responded
- 45% ORR (95% CI, 37–53; P=0.001) with KEYTRUDA vs 28% (95% CI, 21–36) with chemotherapy
- 4% CR and 41% PR with KEYTRUDA vs 1% CR and 27% PR with chemotherapy
Durable responses demonstrated
- Median DOR not reached (range: 1.9+ – 14.5+ months) with KEYTRUDA vs 6.3 months (range: 2.1+ – 12.6+ months) with chemotherapy
KEYNOTE-024 study design1: A randomized, open-label, multicenter, active-controlled, phase 3 trial, which included
treatment-naïve patients with mNSCLC whose tumors had high PD-L1 expression (TPS ≥50%). Patients with EGFR or
ALK genomic tumor aberrations; an autoimmune disease that required systemic therapy within 2 years of treatment; a
medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within 26
weeks were ineligible. Patients were randomized to receive KEYTRUDA 200 mg Q3W (n=154) or investigator’s choice
platinum-containing chemotherapy (n=151; including pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+cisplatin,
gemcitabine+carboplatin, or paclitaxel+carboplatin; patients with nonsquamous NSCLC could receive pemetrexed
maintenance). Treatment with KEYTRUDA continued until progression of disease, unacceptable toxicity, or for up to 24
months. Patients on chemotherapy who experienced disease progression were offered KEYTRUDA. The main efficacy
outcome measure was progression-free survival (PFS). Additional efficacy outcome measures were OS and objective
response rate (ORR).
For patients with PD-L1 ≥50%:
Single-agent pembrolizumab
(KEYTRUDA) is the preferred first-line therapy for patients with
nonsquamous or squamous mNSCLC, and with no EGFR
mutations or ALK rearrangements.
In advanced NSCLC with no EGFR or ALK genomic tumor aberrations and PD-L1 ≥1%
KEYNOTE-042 study design4: Phase 3, randomized, multicenter, active-controlled trial in systemic treatment–naïve patients
with locally advanced or metastatic NSCLC whose tumors expressed PD-L1 with a ≥1% TPS. Patients with EGFR or ALK
genomic tumor aberrations; autoimmune disease that required systemic therapy within 2 years of treatment; a medical
condition that required immunosuppression; or patients who had received more than 30 Gy of thoracic radiation within the
prior 26 weeks were ineligible. Patients were randomized to receive KEYTRUDA 200 mg Q3W (n=637) or investigator’s
choice of pemetrexed + carboplatin or paclitaxel + carboplatin (n=637; patients with nonsquamous NSCLC could receive
pemetrexed maintenance). Treatment continued until progression of disease, unacceptable toxicity, or up to 24 months. The
primary efficacy outcome measure was OS. Secondary efficacy outcome measures were PFS and ORR. PFS and ORR
were assessed by blinded independent central review (BICR) per RECIST v1.1 (modified to follow a maximum of 10 target
lesions and a maximum of 5 target lesions per organ).
aOriginally published by the American Society of Clinical Oncology. Reck M, Rodríguez-Abreu D, Robinson AG, et al: J Clin Oncol. 37(7), 2019:537–546. Reprinted with permission. © 2019 American Society of Clinical Oncology. All rights reserved.
bHR based on the stratified Cox proportional hazard model for the interim analysis; P value based on stratified log-rank test.
cP value is compared with 0.0118 of the allocated alpha for the interim analysis.
dBased on the protocol-specific final OS analysis conducted at 169 events, which occurred 14 months after the interim analysis.
eBased on the stratified Cox proportional hazard model.1
fSee NCCN Guidelines® for detailed recommendations, including combination regimens, in patients with no targetable genomic tumor aberrations.
gSee NCCN Guidelines for recommendations specific to genetic alterations.
hBased on a stratified log-rank test; compared to a P value boundary of 0.0291.
iNot evaluated for statistical significance as a result of the sequential testing procedure for the secondary end points.
jNot significant compared to a P value boundary of 0.0291.
kBased on observed duration of response.
Preferred intervention = Intervention that is based on superior efficacy, safety, and evidence; and, when appropriate, affordability.3
Category 1 = Based upon high-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate.3
ALK = anaplastic lymphoma kinase; CI = confidence interval; CR = complete response; DOR = duration of response; EGFR = epidermal growth factor receptor; HR = hazard ratio; mNSCLC = metastatic NSCLC; NR = not reached; NS = not significant; NSCLC = non–small cell lung cancer; OS = overall survival; PD-L1 = programmed death ligand 1; PR = partial response; Q3W = every 3 weeks; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1; TPS = tumor proportion score.