A phase II study of sunitinib (S) plus erlotinib (E) in advanced renal carcinoma (RCC).

Abstract

4528^ Background: Overexpression of EGFR is frequent in RCC, but EGFR-directed therapies have shown little single-agent activity. Preclinical studies suggest that combined VEGF and EGFR inhibition may overcome resistance. We performed a phase II study of S with E in patients with advanced RCC. Results of the dose-escalation phase were previously reported (Ryan et al., GU ASCO 2008). We now report the results of the efficacy phase. Methods: Eligibility included advanced clear cell or papillary RCC, measurable disease, performance status 0-2, and no prior S or anti-EGFR therapy. The dose as determined by the escalation phase was E 150 mg daily with S 50 mg 4/2 wk schedule. Response was determined using RECIST at 6 weeks and every 12 weeks thereafter. The primary endpoint was 8-month PFS. A 70% 8-month PFS rate would be considered promising, given the ∼50% rate in previous phase II studies with single-agent sunitinib. Results: 37 patients were enrolled from 6/07 to 7/09; all are evaluable for efficacy and toxicity. Patient characteristics: Median age 58 (range 24-78); clear cell/papillary/mixed = 89%/8%/3%; prior nephrectomy 84%; prior sorafenib 22%; see Table. Most common adverse events were diarrhea (95%), rash (92%), fatigue (81%), and dysgeusia (78%). Most common grade 3-4 events were hypophosphatemia (22%), rash (22%), fatigue (14%), and diarrhea (11%). 32% underwent dose reduction of both drugs; 14% and 3% underwent reduction of only E or S, respectively. The 8-month PFS rate was 39% (95% CI: 22-55). Median PFS was 5.8 months (95% CI: 4.1-9.7) and estimated median OS is 24.3 months (95% CI: 15.1-24.3). PFS for subgroups are shown in table. Best response was PR 22%, SD 62%, and PD 16%. Conclusions: While S and E are combinable, rash and diarrhea are notable overlapping toxicities. The 8- month PFS rate does not suggest improvement over S monotherapy. Patient selection and dose reductions may have influenced results. N % PFS (months) 95% CI (months) First-line 19 51 5.1 2.8-6.9 Prior-treated 18 49 9.7 4.1-17.9 Prior cytokine 10 27 15.3 3.1-17.9 No prior cytokine 27 73 5.1 4.1-6.9 MSKCC risk Favorable 8 22 10.1 1.3-NR Intermediate 24 65 6.9 5.1-12.4 Poor risk 5 14 1.7 1.3-4.3 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, Gerson Lehrman Group, Novartis, Onyx, OSI, Pfizer, Wyeth Bayer, Novartis, Onyx, Pfizer, sanofi-aventis, Wyeth Amgen, Bayer, Novartis, Onyx, OSI, Pfizer In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2010 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest.