Updated results of CABINET trial/alliance A021602: cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy

MD Thorvardur R. Halfdanarson,; PhD Susan Geyer,; MS Tyler Zemla,; MD, PhD Michael V. Knopp,; MD Spencer Behr,; MPH Sydney Pulsipher,; PhD Fang-Shu Ou,; MD Jared Acoba,; MD Ardaman Shergill,; MD Edward M. Wolin,; MD, MPH Bhavana Konda,; MD Nikolaos A. Trikalinos,; MD Bernard Tawfik,; MD Nitya Raj,; MD Shagufta Shaheen,; MD Namrata Vijayvergia,; MD, MS Arvind Dasari,; MD Jonathan R. Strosberg,; MD Elise C. Kohn,; MD, MMSc Matthew H. Kulke,; MD Eileen M. O; MD, MPH Jeffrey A. Meyerhardt,; MD & MPH Jennifer A. Chan

doi:10.1530/endoabs.108.C9

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Endocrine Abstracts (2024) 108 C9 | DOI: 10.1530/endoabs.108.C9

NANETS2024 17th Annual Multidisciplinary NET Medical Symposium NANETS 2024 Clinical - Chemo/SSA/Biologics (19 abstracts)

Updated results of CABINET trial/alliance A021602: cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy

Thorvardur R. Halfdanarson, MD¹, Susan Geyer, PhD², Tyler Zemla, MS², Michael V. Knopp, MD, PhD³, Spencer Behr, MD⁴, Sydney Pulsipher, MPH², Fang-Shu Ou, PhD², Jared Acoba, MD⁵, Ardaman Shergill, MD⁶, Edward M. Wolin, MD⁷, Bhavana Konda, MD, MPH⁸, Nikolaos A. Trikalinos, MD⁹, Bernard Tawfik, MD¹⁰, Nitya Raj, MD¹¹, Shagufta Shaheen, MD¹², Namrata Vijayvergia, MD¹³, Arvind Dasari, MD, MS¹⁴, Jonathan R. Strosberg, MD¹⁵, Elise C. Kohn, MD¹⁶, Matthew H. Kulke, MD, MMSc¹⁷, Eileen M. O’Reilly, MD¹¹, Jeffrey A. Meyerhardt, MD, MPH¹⁸, Jennifer A. Chan MD & MPH¹⁸

Author affiliations

¹Mayo Clinic Comprehensive Cancer Center, Rochester, MN; ²Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN; ³Wright Center of Innovation & IROC, University of Cincinnati, Cincinnati, OH; ⁴University of California, San Francisco, San Francisco, CA; ⁵University of Hawaii Cancer Center, Honolulu, HI; ⁶Alliance Protocol Operations Office, University of Chicago, Chicago, IL; ⁷Mount Sinai Medical Center, New York, NY; ⁸The Ohio State University Comprehensive Cancer Center, Columbus, OH; ⁹Washington University School of Medicine and Siteman Cancer Center, St. Louis, MO; ¹⁰University of New Mexico Comprehensive Cancer Center, Albuquerque, NM; ¹¹Memorial Sloan Kettering Cancer Center, New York, NY; ¹²Stanford Cancer Center, Stanford, CA; ¹³Fox Chase Cancer Center, Philadelphia, PA; ¹⁴MD Anderson Cancer Center, Houston, TX; ¹⁵Moffitt Cancer Center, Tampa, FL; ¹⁶National Cancer Institute, Bethesda, MD; ¹⁷Boston Medical Center and Boston University, Boston, MA; ¹⁸Dana-Farber Cancer Institute, Boston, MA

Background: NETs are sensitive to VEGF pathway inhibitors. We compared cabozantinib (CABO), a multi-kinase inhibitor targeting VEGFR, c-MET, AXL and RET, with placebo (PB) in a phase 3 trial including previously treated patients (pts) with advanced NET (NCT03375320). The study was stopped early and unblinded, per DSMB recommendations, based on interim results showing improvement in PFS by local radiology assessment (ESMO 2023). Final analyses of PFS by blinded independent central review (BICR), objective response rate (ORR), subgroup analyses, and safety are presented.

Methods: Pts with locally advanced or metastatic extra-pancreatic NET (epNET) or pancreatic NET (pNET) were randomized 2:1 in separately powered cohorts to receive CABO 60 mg daily vs PB. Eligibility: progression by RECIST within 12 months (mo) prior to registration, ≥ 1 prior therapy. Prespecified primary endpoint: PFS by BICR. Secondary endpoints: ORR, overall survival (OS), safety.

Results: 203 pts with epNET and 95 pts with pNET were randomized through the data cutoff of 8/24/2023. Primary tumor sites for pts with epNET included GI tract 57%, lung 19%, unknown 12%. In both cohorts, CABO significantly improved PFS by BICR and resulted in higher confirmed ORR (Table). Across clinical subgroups, including primary tumor site and prior anticancer therapy, PFS favored CABO. Grade 3+ treatment-related adverse events (AEs) were higher in the CABO arm; no new safety signals were noted. The most common ≥ grade 3 treatment-related adverse events in the epNET cohort included hypertension (21%), fatigue (13%) and diarrhea (11%); in the pNET cohort, they included hypertension (22%), fatigue (11%) and thromboembolic events (11%).

Table 1. Progression-free survival and objective tumor response by BICR of patients enrolled in the epNET and pNET cohorts
	CABO - epNET (n = 134)	PB - epNET (n = 69)	CABO - pNET (n = 64)	PB - pNET (n = 31)
Median PFS (BICR), months	8.5	4.0	13.8	4.5
Stratified HR (95% CI)	0.38 (0.25-0.58)	Ref	0.23 (0.12-0.42)	REF
Ref Stratified log-rank p-value	P < 0.0001		P < 0.0001
Confirmed ORR (BICR), n (%)
Partial response	7 (5%)	0	12 (19%)	0
Stable disease	87 (65%)	37 (54%)	39 (61%)	17 (55%)
Progressive disease	15 (11%)	24 (35%)	5 (8%)	12 (39%)
Not evaluable/missing	25 (19%)	8 (12%)	8 (13%)	2 (6%)

Conclusions: CABO demonstrates significant improvement in PFS by BICR in epNET and pNET. AEs are consistent with the known safety profile of CABO. CABO may be a new treatment option for pts with previously treated, advanced NET.

ABSTRACT ID28623