Randomized phase III study (SPEAR) of picoplatin plus best supportive care (BSC) or BSC alone in patients (pts) with SCLC refractory or progressive within 6 months after first-line platinum-based chemotherapy. (2010)

7002^ Background: Picoplatin is a new platinum compound designed to overcome platinum resistance and has demonstrated less neurotoxicity and nephrotoxicity than other platinum agents. The SPEAR study was designed to assess the efficacy and safety of picoplatin + BSC (pico) vs. BSC for the treatment of SCLC, nonresponsive or progressive within 6 months of platinum-based therapy. Methods: 401 pts were randomly assigned 2:1 to pico IV 150 mg/m2 q3w, n = 268 or BSC, n = 133. Overall survival (primary endpoint), progression-free survival (PFS), response rate, and time-to-progression (TTP) were assessed. Adverse events (AEs) were assessed with NCI-CTCAE v3. Results: Pt demographics were balanced with a median age of 58 yrs, 84% male, 88% Caucasian, 85% PS 0-1, 15% PS 2. Median pico cycles = 3 (1-15). With a hazard ratio (HR) of 0.8, median survival time (MST) for pico vs BSC was 21 wks (CI 19-25) vs 20 wks (CI 16-24) (p = 0.09). However, refractory pts (pts who never responded or pts who relapsed within 45 days) had a significant improvement in survival when treated with pico vs BSC. After progression, 28% vs. 41% of pts received post study chemotherapy for pico vs BSC. In pts who did not receive post study chemotherapy, MST for pico (n = 194) was 18 wks (CI 16-20) and for BSC (n = 79) was 14 wks (CI 11-20). For pico vs. BSC, PFS was 9 vs. 7 wks (HR 0.8, p = 0.03) and TTP was 11 vs. 7 wks (HR 0.61, p = 0.02). AEs for BSC pts were associated with SCLC. On pico, grade 3/4 AEs > 10% were thrombocytopenia (44%), anemia (29%), neutropenia (18%), asthenia (11%). Febrile neutropenia occurred in < 1%. No pico treatment-related deaths due to hematologic toxicity were observed. Conclusions: Analysis of survival (321 events) did not achieve statistical significance (p = 0.09); imbalanced use of post study chemotherapy may have impacted this result. Refractory pts who never responded or relapsed within 45 days had a significant improvement in survival with picoplatin. Picoplatin was well-tolerated with manageable hematological toxicity. The study supports the use of picoplatin in the 2nd-line treatment of SCLC after platinum therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Poniard Pharmaceuticals Poniard Pharmaceuticals 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.