Abstract 212P
Background
Cabozantinib and temozolomide are effective agents for the treatment of well-differentiated neuroendocrine tumors. Whether combining cabozantinib and temozolomide might be safe and effective in patients with gastroenteropancreatic or lung NETs is currently unknown.
Methods
We performed an open-label, single-arm, multicenter, phase II trial of cabozantinib 40 mg daily plus temozolomide 100 mg/m2 one week on/one week off in patients with advanced, gastroenteropancreatic or lung, well-differentiated NET with evidence for progressive disease on prior treatment. The primary endpoint was overall response rate (ORR) as assessed by RECIST 1.1 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and 1-year OS.
Results
37 patients were enrolled of whom 27 were assessable for response. Primary sites included pancreas (13 patients), small bowel (9), lung (9), colon (2), stomach (1), gallbladder (1), unknown (2). 11 patients had G1 tumors, 22 patients had G2 tumors and 4 patients had G3 tumors. Patients had received a median of 2 lines of prior treatment. Among evaluable patients, an ORR of 22% was recorded, with a clinical benefit rate (CR+PR+SD) of 100%. After a median follow-up of 10 months, median PFS was 28.5 months (95% CI, 22-28.5 months). Median OS was not reached and the 1-year OS rate was 77.6% (±7%). Ten patients discontinued the treatment before the first restaging due to adverse events (n=9) or withdrawal of consent (n=1). The most common G3/G4 treatment-related adverse events included diarrhea (18%), thrombocytopenia (12%), abdominal pain (6%), oral mucositis (6%) and anemia (6%).
Conclusions
The combination of cabozantinib and temozolomide shows promising antitumor activity in patients with NETs. While tolerability appears to be an issue, the relatively high rate of toxicities leading to early treatment discontinuation observed in this study should be weighted against the characteristics of a heavily pretreated patient population.
Clinical trial identification
EudraCT 2020-001898-78.
Legal entity responsible for the study
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples (Italy).
Funding
Ipsen (no-profit trial- Ipsen provided cabozantinib).
Disclosure
All authors have declared no conflicts of interest.