A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients with Newly Diagnosed Stage IV Squamous Cell Lung Cancers

Purpose: Gemcitabine and albumin-bound paclitaxel (ABP) exhibit synergistic anti-tumor efficacy, with ABP serving to increase the intratumoral gemcitabine concentration. Both drugs are active in squamous cell lung cancers (SQCLCs) and are conventional partners for carboplatin. We hypothesized that combining gemcitabine and ABP would enhance the anti-tumor activity in patients with advanced SQCLCs. Experimental Design: This was a Simon two-stage, open-label, single-arm, multicenter phase II study that enrolled patients between August 1, 2015 and June 1, 2018. We enrolled 37 patients with chemotherapy-naive, PD-L1 low/unknown advanced stage IV SQCLC. Patients were administered weekly intravenous gemcitabine (1000 mg/m2) plus ABP (100 mg/m2) in a 3 week on, 1 week off schedule during Stage 1 and a 2 week on, 1 week off schedule in Stage 2. The primary endpoint was best objective response rate (ORR). Next-generation sequencing by MSK-IMPACT was used to calculate tumor mutation burden and genome doubling and assess somatic variants for correlations with efficacy. Results: Thirty-two patients were evaluable for response assessment. The study satisfied its primary endpoint, with confirmed partial responses in 18 of 32 patients and a complete response in 1 patient (ORR 59%, 95% CI 42% to 74%). Median progression-free survival (PFS), a secondary endpoint, was 7.5 (95% CI 6.7 to 10.5) months. There were no unexpected toxicities. Conclusions: Gemcitabine plus ABP was a safe, tolerable, and effective first-line therapy for patients with chemotherapy-naive SQCLCs, with an ORR and median PFS substantially higher than carboplatin doublet regimens and efficacy comparable to carboplatin plus taxane plus pembrolizumab.