A potential new enriching trial design for selecting non‐small‐cell lung cancer patients with no predictive biomarker for trials based on both histology and early tumor response: further analysis of a thalidomide trial

There are few predictive biomarkers for antiangiogenic trials in lung cancer. We examine a potential treatment strategy in which a patient group is enriched using both histology and an early assessment of response during standard chemotherapy, and where a new agent is given for the remainder of chemotherapy and as maintenance. We performed a retrospective analysis of 722 stage IIIB/IV non‐small‐cell lung cancer patients from a double‐blind placebo‐controlled trial of thalidomide or placebo 100–200 mg/day, combined with gemcitabine/carboplatin (for up to four cycles), then given as single agent maintenance therapy. There was a significant statistical interaction between treatment and histology, with a possible benefit among squamous cell cancer ( SCC ) patients. We examined 150 SCC patients who were “nonprogressors” (stable disease or complete/partial response) after completing the second chemotherapy cycle. Endpoints were progression‐free survival ( PFS ) and overall survival ( OS ). Among the 150 patients nonprogressors after cycle 2 (thalidomide, n  =   72; placebo, n  =   78; baseline characteristics were similar), the hazard ratios ( HR s) were: OS  = 0.76 (95% CI : 0.54–1.07) and PFS  = 0.69 (95% CI : 0.50–0.97). In 57 patients who had a complete/partial response, the HR s were: OS  = 0.63 (95% CI : 0.34–1.15) and PFS  = 0.50 (95% CI : 0.28–0.88). SCC patients who were nonprogressors after 2 cycles of standard chemotherapy showed evidence of a benefit from thalidomide when taken for the remainder of chemotherapy and as maintenance. This strategy based on histology and, importantly, early assessment of tumor response, as a means of patient enrichment, could be examined in other lung cancer studies. Such an approach might be suitable for trials where there are no predictive biomarkers.