A retrospective analysis of outcomes across histological subgroups in a three-arm phase III trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin for advanced non-small cell lung cancer

Purpose: Three phase III trials have shown pemetrexed to be associated with improved clinical outcomes among patients with adenocarcinoma and large cell histology compared with patients with squamous histology in advanced non-small cell lung cancer (NSCLC). The current retrospective analysis examined whether differences were present by histology in a three-arm trial of gemcitabine-carboplatin (GCb) or gemcitabine-paclitaxel (GP) versus a standard regimen of paclitaxel-carboplatin (PCb). Materials and methods: 1135 chemonaïve patients with stage IIIB or IV NSCLC were randomly allocated to receive: gemcitabine 1000mg/m² days 1 and 8 plus carboplatin area under the curve (AUC) 5.5 day 1 (GCb); or gemcitabine 1000mg/m² days 1 and 8 plus paclitaxel 200mg/m² day 1 (GP); or paclitaxel 225mg/m² plus carboplatin AUC 6.0 day 1 (PCb). Cycles were repeated every 21 days up to 6 cycles or disease progression. Clinical results were retrospectively analyzed in by patient histology. Results: 202 patients (17.8%) had squamous, 555 (48.9%) had adenocarcinoma, 45 (4.0%) had large cell, and 333 (29.3%) had another histologic type. The overall response rate for squamous patients was greater than non-squamous (35.1% versus 27.8%, P=0.04). Median survival (9.5 months for squamous and 8.3 months for non-squamous) and median time to progression (5.0 months for squamous and 4.4 months for non-squamous) did not significantly vary by histologic group. For squamous histology, median survival was 6.6 months for GCb, 10.2 months for GP, and 10.3 months for PCb. For non-squamous disease, median survival was 8.2 months for GCb, 8.4 months for GP, and 8.3 months for PCb. A formal test for a histology-by-treatment interaction effect between GCb and PCb was significant (P=0.04). Conclusion: In this trial of commonly used agents for advanced NSCLC, overall survival and time to progression were similar when comparing patients across histologies. The effect of treatment, however, varied across histologies.