In this phase II trial, irinotecan, carboplatin, and bevacizumab achieved response, TTP, and survival outcomes that compare favorably with larger randomized trials using chemotherapy alone. Randomized trials can best assess bevacizumab's impact in the first-line treatment of extensive-stage SCLC.

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3529 Background: Cancer stem cells are considered to be fundamentally important for resistance, recurrence and metastasis. Napabucasin is a first-in-class cancer stemness inhibitor in development identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al, PNAS 112(6):1839, 2015). Preclinically, napabucasin sensitizes cancer cells to chemotherapy and targeted agents. Methods: A phase Ib/II multi-center study in mCRC pts was done to confirm the RP2D and signs of anti-cancer activity of napabucasin in combination with FOLFIRI +/- Bev. Pts received napabucasin 240 mg PO BID with bi-weekly FOLFIRI IV +/- Bev 5 mg/kg until disease progression or other discontinuation criterion. Results: 82 pretreated mCRC pts were enrolled (ITT); including 32 (39%) previously treated with FOLFIRI +/- bev. Of the 82 pts, 48 received FOLFIRI and 34 FOLFIRI plus bev in combination with napabucasin. There was no dose-limiting or unexpected toxicity or significant PK interactions. Most common adverse events (AEs) included grade 1/2 diarrhea, cramping, nausea, vomiting, fatigue and anorexia with grade 4 diarrhea in 1 pt and 27 pts with grade 3 AEs including: diarrhea (15), fatigue (5), dehydration (1), electrolyte imbalance (4), abdominal pain (1), vomiting (1) and weight loss (1), which resolved with dose reduction and supportive care. Disease control (CR+PR+SD) was observed in 55 of 66 pts who received RECIST evaluation (83%), with 1 CR (1.5%), 13 PR (20%) (33-100% regression) and 27 SD with tumor regression (41%). Conclusions: This phase Ib/II study confirmed that napabucasin can be safely combined with FOLFIRI +/- bev, and shows encouraging signs of efficacy in pretreated mCRC pts, including pts previously treated with FOLFIRI +/- bev. Clinical trial information: NCT02024607. [Table: see text]

7085 Background: Targeting VEGF has proven to be an effective tx strategy in many solid tumors including non-small cell lung cancer. VEGF expression in SCLC provides rationale for studying B in addition to chemoradiotherapy. Methods: The endpoints of this multicenter community-based study were to assess the safety, response rate (RR), and progression-free survival (PFS) of I/C/RT followed by B in patients (pts) with LS-SCLC. Tx included: C AUC = 5 IV D1, I 50mg/m2 IV D1,8 Q 21D x 4 cycles, and RT 1.8 Gy daily to a total of 61.2 Gy, beginning with the 3rd cycle. 3rd and 4th cycles were 28D each. Pts were restaged after 4 cycles. If no progressive disease (PD) pts received B 10 mg/kg IV Q 14D x 10 doses. Eligibility included: measurable disease, ECOG PS 0–1, informed consent, and no new brain metastases or bleeding. Results: Fifty-seven pts were enrolled from 8/03 to 10/04. Forty-five pts (79%) and 41 pts (72%) received planned tx with I/C/RT and B, respectively. The range of follow-up is 14–28 months. Baseline features: median age 65 years (42–80); male/female, 37%/63%; ECOG PS 0,1: 26%/74%. Grade (G) 3/4 non-hematologic toxicity: diarrhea (9%), DVT (4%), vomiting (11%), and fatigue (9%). G3/4 hematologic toxicity: neutropenia (37%), anemia (5%), and thrombocytopenia (13%). Only 9% of pts experienced G3/4 toxicity during B tx (1 pt each: DVT, hypokalemia, depression, pain, and colon perforation). There were 2 tx-related deaths (both from respiratory failure; 1 and 2 doses of B had been administered). Complete/partial responses were observed in 15 pts (26%)/31 pts (54%), respectively, for an overall RR of 80% (95% CI 70%-90%). Four pts had stable disease, and 5% had PD (4 pts were unevaluable.) 1- and 2-year PFS rates were 63% and 54%, respectively. 1- and 2- year overall survival (OS) rates were 71% and 29%, respectively. Median OS was 15 months. Conclusions: The safety, RR, and 1- and 2-year survival results of I/C/RT followed by B compare favorably with standard tx for LS-SCLC; and B may improve PFS. Assessing the role of B as maintenance tx in improving OS in this setting will require randomized trials. [Table: see text]