In nonsquamous mNSCLC with no EGFR or ALK genomic tumor aberrations
- Median OS not reached (95% CI, NR–NR) with KEYTRUDA + plat/pem vs 11.3 months with plat/pem alone (95% CI, 8.7–15.1).
- Events observed: 31% (127/410) with KEYTRUDA + plat/pem and 52% (108/206) with plat/pem alone.
NCCN® RECOMMENDATION
UPDATED OVERALL SURVIVAL DATA
LIMITATION: The protocol-specified final analysis occurred after an interim analysis that demonstrated the superiority of KEYTRUDA + plat/pem in overall survival compared to plat/pem alone. No formal statistical testing was planned for the final analysis and, therefore, no statistical conclusions can be drawn.
- Median OS: 22.0 months with KEYTRUDA + plat/pem (95% CI, 19.5–25.2) vs 10.7 months with plat/pem alone (95% CI, 8.7–13.6).
- Events observed: 52% (213/410) with KEYTRUDA + plat/pem and 70% (144/206) with plat/pem alone.
Choose KEYTRUDA + plat/pem first line for all appropriate patients with nonsquamous mNSCLC, including PD-L1 nonexpressers.
NONEXPRESSERS
LIMITATION: KEYNOTE-189 was not powered to detect differences in the treatment effect in this subgroup; therefore, results from this exploratory analysis should be interpreted with caution because of the modest patient numbers and potential imbalances in baseline characteristics within the subgroup.
EXPRESSERS
LIMITATION: KEYNOTE-189 was not powered to detect differences in the treatment effect in this subgroup; therefore, results from this exploratory analysis should be interpreted with caution because of the modest patient numbers and potential imbalances in baseline characteristics within the subgroup.
APPROPRIATE PATIENTS
Significantly improved
- 48% reduction in the risk of disease progression or death with KEYTRUDA + plat/pem vs plat/pem alone (HR=0.52; 95% CI, 0.43–0.64; P<0.0001)b
- 8.8-month median PFS (95% CI, 7.6–9.2) with KEYTRUDA + plat/pem vs 4.9 months (95% CI, 4.7–5.5) with plat/pem alone
- Events observed: 60% with KEYTRUDA + plat/pem (244/410) and 81% (166/206) with plat/pem alone
More than doubled
- 48% ORR (95% Cl, 43–53) with KEYTRUDA + plat/pem vs 19% (95% CI, 14–25) with plat/pem alone (P<0.0001)d
- 0.5% CR and 47% PR with KEYTRUDA + plat/pem vs 0.5% CR and 18% PR with plat/pem alone
Durable responses demonstrated
- 11.2-month median DOR (range: 1.1+ – 18.0+ months) with KEYTRUDA + plat/pem vs 7.8 months (range: 2.1+ – 16.4+ months) with plat/pem alone
KEYNOTE-189 study design1: Phase 3, randomized, multicenter, double-blind, active-controlled trial in systemic therapy–naïve patients with metastatic nonsquamous NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or
ALK genomic tumor aberrations. Patients with 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, cisplatin or
carboplatin, and pemetrexed intravenously Q3W for 4 cycles followed by KEYTRUDA 200 mg for up to 24 months and
pemetrexed Q3W (n=410); or cisplatin or carboplatin and pemetrexed intravenously Q3W for 4 cycles followed by pemetrexed
Q3W (n=206). Treatment continued until progression of disease or unacceptable toxicity. Primary efficacy outcome measures
were OS and PFS 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). Secondary efficacy outcome measures were ORR and
duration of response (DOR). Patients receiving chemotherapy and pemetrexed who experienced disease progression could
cross over to receive KEYTRUDA as monotherapy.
For patients with or without PD-L1 expression:
Pembrolizumab (KEYTRUDA), in combination with pemetrexed and platinum chemotherapy, is recommended (category 1 and preferred) as first-line treatment for patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations.
aFrom The New England Journal of Medicine, Gandhi L, Rodríguez‑Abreu D, et al; for the KEYNOTE-189 Investigators. Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med. 2018;378(22):2078–2092. Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
bHR based on the stratified Cox proportional hazard model with Efron’s method of tie handling; P value based on stratified log-rank test.2
cHR based on the stratified Cox proportional hazard model.1
dResponse: Best objective response as confirmed complete response or partial response; P value based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy, and smoking status.
eSee NCCN Guidelines® for detailed recommendations, including combination regimens, in patients with no targetable genomic tumor aberrations.
fSee NCCN Guidelines for recommendations specific to genetic alterations.
Preferred intervention = Intervention that is based on superior efficacy, safety, and evidence; and, when appropriate, affordability.4
Category 1 = Based upon high-level evidence there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate.4
1L = first line; ALK = anaplastic lymphoma kinase; CI = confidence interval; CR = complete response; EGFR = epidermal growth factor receptor; HR = hazard ratio;
mNSCLC = metastatic NSCLC; NR = not reached; NSCLC = non–small cell lung cancer; ORR = objective response rate; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival; plat/pem = cisplatin or carboplatin and pemetrexed; PR = partial response; Q3W = every 3 weeks; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1.