In squamous mNSCLC
- Median OS: 15.9 months (95% CI, 13.2–NE) with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound vs 11.3 months (95% CI, 9.5–14.8) with carbo + paclitaxel or paclitaxel protein-bound
- Events observed: 31% (85/278) with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound and 43% (120/281) with carbo + paclitaxel or paclitaxel protein-bound
NCCN® RECOMMENDATION
Choose KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound first line for all appropriate patients with squamous mNSCLC, including PD-L1 nonexpressers.
NONEXPRESSERS
LIMITATION: KEYNOTE-407 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-407 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
44% reduction in the risk of disease progression or death with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound
- HR=0.56; 95% CI, 0.45–0.70; P<0.0001b
- 6.4-month median PFS (95% CI, 6.2–8.3) with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound vs 4.8 months (95% CI, 4.3–5.7) with carbo + paclitaxel or paclitaxel protein-bound
- Events observed: 55% (152/278) with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound and 70% (197/281) with carbo + paclitaxel or paclitaxel protein-bound
Over half of patients responded
- 58% ORR (95% CI, 48–68) with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound vs 35% (95% CI, 26–45) with carbo + paclitaxel or paclitaxel protein-bound (P=0.0008e) in a primary analysisf
Durable responses demonstrated
- 7.2-month median DOR (range: 2.4–12.4+ months) with KEYTRUDA + carbo + paclitaxel or paclitaxel protein-bound vs 4.9 months (range: 2.0–12.4+ months) with carbo + paclitaxel or paclitaxel protein-boundf
KEYNOTE-407 study design1: Phase 3, randomized, multicenter, double-blind, placebo-controlled trial in systemic therapy–naïve patients with metastatic squamous NSCLC, regardless of PD-L1 tumor expression status. 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 Q3W, carboplatin Q3W, and either paclitaxel Q3W or paclitaxel protein-bound Q1W intravenously for four 3-week cycles followed by KEYTRUDA 200 mg Q3W (n=278); or carboplatin Q3W and either paclitaxel Q3W or paclitaxel protein-bound Q1W intravenously for four 3-week cycles followed by placebo Q3W (n=281). Treatment continued until progression of disease, unacceptable toxicity, or up to 24 months. The main efficacy outcome measures were OS, PFS, and ORR. An additional efficacy outcome measure was duration of response (DOR). PFS, ORR, and DOR 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). Patients receiving carboplatin and either paclitaxel or paclitaxel protein-bound alone 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
carboplatin and either paclitaxel or paclitaxel protein-bound, is
recommended (category 1 and preferred) as first-line therapy for patients
with metastatic squamous NSCLC.
aFrom The New England Journal of Medicine, Paz-Ares L, Luft A, Vicente D, et al; for the KEYNOTE-407 investigators, Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer. N Engl J Med. 2018;379(21):2040–2051. Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from
Massachusetts Medical Society.
bHR based on the stratified Cox proportional model; P value based on stratified log-rank test.
cFrom The New England Journal of Medicine, Paz-Ares L, Luft A, Vicente D, et al; for the KEYNOTE-407 investigators, Supplement to: Pembrolizumab plus chemotherapy for squamous non–small-cell lung cancer. N Engl J Med. 2018;379(21):2040–2051. Copyright © 2018 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.
dHR based on the stratified Cox proportional hazard model.1
eBased on stratified Miettinen-Nurminen test.
fORR primary analysis and DOR analysis were conducted with the first 204 patients enrolled.
gSee NCCN Guidelines® for detailed recommendations, including combination regimens, in patients with no targetable genomic tumor aberrations.
hSee NCCN Guidelines for recommendations specific to genetic alterations.
iPembrolizumab/carboplatin/paclitaxel (or albumin-bound paclitaxel) is recommended (category 1 preferred) as first-line therapy for certain patients with metastatic squamous NSCLC.4
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; albumin-bound paclitaxel = paclitaxel protein-bound; carbo = carboplatin; CI = confidence interval; HR = hazard ratio; mNSCLC = metastatic NSCLC; NE = not estimable; NSCLC = non–small cell lung cancer; ORR = objective response rate; OS = overall survival; PD-L1 = programmed death ligand 1; PFS = progression-free survival; Q1W =
every week; Q3W = every 3 weeks; RECIST v1.1 = Response Evaluation Criteria In Solid Tumors v1.1.