We've had a very nasty 20 days...so I thought I'd paste some paragraphs from analyst reports dating from after ph2 (Oppenheimer, Lazard,). Not sure if these guys ever updated their analysis...these long periods between trials are brutal..."no news, sell!". Who knows where this is going...but these are a reminder why some of us have stayed the course. #1 In a subset of patients with nonsquamous NSCLC, overall survival was a statistically significant 43.1 weeks for the ‘197 + Tarceva arm versus 29.4 weeks for Tarceva alone (HR=0.58, P<0.05), a 14-week benefit, when data were adjusted for various imbalances in key prognostic factors, such as EGFR and KRAS mutational status favoring the placebo arm, using a Cox regression analysis pre-specified in the trial protocol. We view the non-squamous subset results as particularly impressive, as this cohort met the OS endpoint with statistical significance, with no added toxicity, despite the crossover effect and not being powered for overall survival.
#2 We note one new data point presented at the ESMO conference was a statistical significant increase in time to new metastases for both the ITT population (7.3 months for ‘197 versus 3.6months for placebo) and 11.0 months compared to 3.6 months in the non-squamous subgroup; these data were not previously presented at ASCO. We view this as important because the results were significant for the overall ITT population, and substantiate current scientific theory that cMet plays a crucial role in the transformation of localized disease to metastatic disease.
#3 The updated results included some interesting points that further establish ARQ-197 as one of the most promising agents for lung cancer. There was a clear trend towards better overall survival in non-squamous patients, although the trial was not powered to show a statistically significant difference. In addition, investigators presented interesting findings on the drug’s ability to delay the formation of new metastases. This property could be a huge advantage in earlier treatment lines, but it will have to be proven prospectively in larger studies. Last, in patients from the Tarceva arm who switched to the combination arm after progressing on Tarceva alone, there was a clear signal including 2 partial responses and several cases of prolonged disease stabilization. Interestingly, the two partial responses were in patients with high MET expression. All the findings above are retrospective or anecdotal, and by themselves cannot justify moving into phase III, but they provide supportive evidence that is in line with the known biologic function of MET.