Bevacizumab, pertuzumab, and sandostatin for patients (pts) with advanced neuroendocrine cancers (NET)

4127 Background: Targeted agents are used to treat well-differentiated NET. Octreotide binds somatostatin receptors and improves time to progression (TTP) of carcinoid tumors, and VEGF pathway targeting improves TTP of pancreatic NET. HER2 overexpression is reported in NET, and pertuzumab blocks HER2 receptor dimerization. This phase II trial combined bevacizumab, pertuzumab, and octreotide LAR for pts with advanced NET. Methods: Pts with advanced well-differentiated NET were enrolled. Pts had ECOG 0-1, and normal end-organ function, including left ventricular ejection fraction (LVEF) ≥50%. Pts received bevacizumab 15 mg/kg IV, pertuzumab 420 mg IV (following an 840 mg loading dose) day 1 of a 21 day cycle, and octreotide LAR 30 mg IM every 28 days. Primary endpoint was objective response rate (ORR). Results: Between 6/10 and 4/11, 43 pts enrolled. 22 M/21 F, med age 62 (33-88), 32 (74%) carcinoid, 11 (26%) PNET. 26% had prior sandostatin, 72% prior surgery, 19% prior radiation, 23% with > 2 previous systemic therapies. Treatment-related grade 3 toxicities included: hypertension (28%), LVEF dysfunction (9%) (reversible with trial drug hold), and diarrhea (7%). No grade 4 toxicity was reported. Median treatment duration was 38 weeks (range: 0 – 76). Chromogranin A values were elevated in 27 pts; 59% had decreases during treatment. Seven pts (16%) achieved objective response [CR: 1 carcinoid (2%), PR: 6 (4 carcinoid, 2 PNET) (14%)]. ORR for carcinoid pts was 15.6%. Median PFS for the entire group was 8.2 months (95% CI: 6.3 – NA). PFS for carcinoid pts was 8.5 months (95% CI: 6.3 – NA); PFS for PNET pts was 6.4 months (95% CI: 3.9 – NA). Median OS has not been reached at 14.3 months followup. Conclusions: The ORR of the combination of bevacizumab, pertuzumab, and octreotide LAR in NET pts was encouraging. Particularly the response rate in carcinoid pts appears higher than historical data, warranting further investigation of this regimen in these pts.