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.
Key Results
- 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
Conclusions:
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