CALGB 30306: A phase II study of cisplatin (C), irinotecan (I) and bevacizumab (B) for untreated extensive stage small cell lung cancer (ES-SCLC)

Abstract

7563 Background: VEGF is expressed in 80% of SCLC. Combining chemotherapy with B is effective in advanced non-small cell lung, breast and colon cancers. Methods: This was a phase II study of C 30 mg/m2 and I 65 mg/m2 days 1 and 8 plus B 15 mg/kg day 1 every 21 days for up to 6 cycles in patients with untreated ES-SCLC, PS 0–2, and adequate organ function. Eligibility required no significant bleeding, uncontrolled hypertension, brain mets or other risk factors for B therapy. An initial safety cohort of ten patients was closely followed for unexpected/severe toxicities. Pretreatment blood was collected for biomarker analysis. Statistical design: primary endpoint 12 mo survival rate > 57% (median survival ≥15 mo). Results: 72 pts were enrolled from 3/05–4/06 with one patient deemed ineligible due to diagnosis NSCLC. Demographics: 51% female; median age 62; PS 0–23%, 1–68%, 2–10%. There were no episodes of grade 3 or greater hemoptysis or other primary hemorrhagic episodes. One patient died after an embolic/thrombotic stroke bled secondarily. Other grade 3/4 toxicities included (%): anemia 5, neutropenia 23, platelets 10, hypertension 6, fatigue 12, diarrhea 17, nausea 11, bowel perforation 2, infection 14, all electrolyte 23, stroke 4, vascular access thrombosis 3. Deaths on therapy 3 (4%): pneumonitis 1, stroke 1, heart failure 1. Preliminary efficacy: CR 2 (3%), PR 42 (59%), SD 9 (13%), PD 1 (1%); ORR 62%; ORR excluding unevaluable (4%)/no data (18%): 80%; median progression free survival 7.0 mo (95% C.I. 6.2,8.0); median overall survival 10.6 mo (95% C.I. 8.5, 11.7); median follow-up 9.5 mo. Pretreatment VEGF/PDGF titers have been measured, reported to the CALGB statistics center, and will be analyzed in relation to response and survival outcomes. Conclusions: Although ES-SCLC often has bulky central disease there was no clinically significant hemoptysis. All patients will be at least 12 months from initiation of therapy by 5/07, and mature response and survival data will be presented. No significant financial relationships to disclose.