Biotech Values

[p3analyze]

If what SNTA has claimed about LDH high predicts better efficacy of its HSP90 inhibitor were true, then VEGFR over-expression should be a predictive marker for VEGFR TKI.

Another possible biomarker for Sorafenib (partly a VEGFR TKI) is K-ras mutation, if you think like a Bayesian who designed the BATTLE trial.

http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=48785

Sorafenib treatment efficacy and KRAS biomarker status in the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial.

Background: BATTLE is a phase II study to prospectively use biomarkers (BM) to guide treatment selection in patients (PTS) with advanced non-small cell lung cancer (NSCLC). This report details a subset analysis of the 8-week disease control rate (DCR) of PTS treated with sorafenib (S) relative to their BM status. Methods: In this phase II, multi-arm study, PTS with pretreated NSCLC, ECOG PS 0-2, consented to fresh core needle biopsies to test, in a research lab, 11 biomarkers related to 4 molecular pathways in NSCLC (EGFR, KRAS, and BRAF gene mutation [PCR-based sequencing], EGFR and Cyclin D1 copy number [FISH], and 6 proteins via IHC [VEGF/R and RXR receptors/Cyclin D1]). PTS were randomized, based on eligibility and BM grouping, into 1 of 4 treatments (erlotinib [E], sorafenib, vandetinab and erlotinib plus bexarotene). PTS randomized to the S arm received S 400 mg orally twice daily until tumor progression or an unacceptable toxicity. Tumor evaluations were performed at baseline and every 8 weeks. The primary objective was to assess DCR. Results: 105 PTS were randomized to receive S: 82% Caucasian, 51% male, 68% adenocarcinoma, 13% squamous cell carcinoma, ECOG status was 0-1 in 89% of PTS. 31 PTS had dose reduction/discontinuation of S. The most common reasons were hand-foot syndrome (n = 6), hemoptysis (n = 5), fatigue, and rash (n = 2 each). DCR for PTS treated with S was 58% (57 in 98 pts with outcome). No responses were observed. In PTS with the presence of a KRAS mutation, DCR was 61% (11/18), in contrast to 31% (4/13) in KRAS-mutated PTS treated with regimens with E. In PTS with an EGFR mutation, DCR was significantly lower (23%, 3/13) when compared to those PTS without the mutation (64%, n = 43/67) (p = 0.012). PTS with EGFR high-polysomy had a lower DC than those who did not (27%, 3/11; 62%, 42/68) (p = 0.048). Conclusions: DCR was improved in PTS treated with S who had KRAS mutations when compared to those who had EGFR mutations or copy number gain. This result suggests that PTS who have KRAS mutations may derive benefit from treatment with S, while those who have EGFR mutation/copy number gain may do worse. Supported by DoD grant W81XWH-6-1-03

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