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Twardowski PW , Tangen CM , Wu X , Plets MR , Plimack ER , Agarwal N , Vogelzang NJ , Wang J , Tao S , Thompson IM , Lara P
Parallel (Randomized) Phase II Evaluation of Tivantinib (ARQ197) and Tivantinib in Combination with Erlotinib in Papillary Renal Cell Carcinoma: SWOG S1107
Kidney Cancer. 2017 Nov 27;1(2) :123-132
PMID: 30334014    PMCID: PMC6179121   
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Background: Papillary renal cell carcinoma (pRCC) is associated with EGFR expression and activation of MET signaling pathway. A randomized multicenter parallel two-stage phase II trial of MET inhibitor tivantinib alone or in combination with EGFR inhibitor erlotinib was conducted in patients with pRCC. Methods: Patients with advanced pRCC and 0-1 prior systemic therapy were randomly assigned to tivantinib 360 mg BID (Arm 1) or tivantinib 360 mg BID plus erlotinib 150 mg daily (Arm 2). Target max accrual was 70 patients (35 per arm) with interim analysis planned after enrollment of 20 patients per arm. Results: Six % of patients had type 1 pRCC, 42% had type 2, and 52% had no subtype assigned. The study was closed after the first stage when both arms yielded RR of 0%. Median progression free survival (PFS) was 2.0 and 3.9 months, and OS was 10.3 and 11.3 months in Arms 1 and 2 respectively. Treatment was well tolerated. Exome of tumor tissue from 16 patients were successfully sequenced using Agilent SureSelect probes. Only 1 of 16 samples harbored MET mutation. Other mutations associated primarily with type 2 pRCC were noted and included CDKN2A, PBRM1, SETD2, KDM6A, FAT1 and NF2. Conclusions: Tivantinib - either alone or in combination with erlotinib has no clinical activity in patients with advanced pRCC. The S1107 cohort had a low proportion of patients with MET alterations. MET remains a reasonable therapeutic target in pRCC, but selection of patient subsets exhibiting MET activation may be required to better benefit from therapy with MET inhibitors.
2468-4570 Twardowski, Przemyslaw W Tangen, Catherine M Wu, Xiwei Plets, Melissa R Plimack, Elizabeth R Agarwal, Neeraj Vogelzang, Nicholas J Wang, Jinhui Tao, Shu Thompson, Ian M Lara, Primo Journal Article Netherlands Kidney Cancer. 2017 Nov 27;1(2):123-132. doi: 10.3233/KCA-170018.