Pembrolizumab plus Chemotherapy as first-line treatment of metastatic squamous NSCLC
New Data suggest Pembrolizumab (Pembro) plus carboplatin and paclitaxel or nab-paclitaxel should become a new standard-of-care for first-line treatment of metastatic squamous non small cell lung cancer (sq NSCLC), irrespective of PD-L-1 expression, according to the authors of the Keynote-407 study (NCT02775435). The study was presented by lead study author Luis G Paz-Ares, University Hospital Madrid at the ASCO 2018.
Source: ASCO Annual Meeting 2018
Keynote-407 is a randomized, placebo-controlled, global study of 560 untreated pts with metastatic sq NSCLC with ECOG 0-1. Patients (Pts) were stratified by type of taxane, PD-L1 (TPS <1% vs ≥1%), and site (East Asia vs other). Pts were randomized 1:1 to receive carboplatin 6 mg/mL/min and paclitaxel 200 mg/m2 every 3 weeks or nab-paclitaxel 100 mg/m2 weekly plus pembro or saline placebo for 4 cycles followed by pembro/placebo for a total of 35 treatments.
Imaging was sent for blinded independent central review (BICR) per RECIST 1.1. The primary endpoints are PFS by BICR and OS in the intent-to-treat population. Alpha is strictly controlled at 0.025 one-sided; PFS and OS each have 0.01. A key secondary endpoint is ORR by BICR in about the first 200 pts randomized with 0.005 alpha. A second interim analysis was performed on PFS and OS when approximately 332 PFS events occurred.
- Pembro plus chemo significantly improved the OS (HR 0,64) over chemo alone (42,7% vs 30,6%, p=0,0008), median OS at IA2 in the ITT group: Pembro 15,9 months (13,2-NE) vs Chemo 11,3 months (9,5-14,8),
- The benefit was observed irrespective of PD-L1 TPS: HR 0,61 for TPS<1%, 0,57 for TPS 1-49%, and 0,64 for TPS>50%.
- PFS (HR 0,56) and ORR (p=0,0004) were also improved with pembro plus chemotherapy and responses were more durable (PFS at IA2 int ITT: Pembro 6,4 months (6,2-8,3) vs Chemo 4,8 months (4,3-5,7).
- AE frequency and severity were mostly similar between arms. No new safety concerns were observed.
- Rates of discontinuation due to AEs were higher in the Pembro plus Chemo-arm,but generally low overall.
- Immune mediated AEs were more frequent in the Pembro arm, with frequency and severity consistent with those observed for pembrolizumab monotherapy
Adding pembro almost doubled the ORR of chemo for pts with untreated metastatic sq NSCLC. Pembro + chemo has a tolerable safety profile.
Paz-Ares LG et al, Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC), #105