Abstract 723O
Background
Angiogenesis plays a key role in development and progression of endocrine neoplasms and synergism has been observed when combined with immune-checkpoint inhibitors in other tumors. We aimed to demonstrate the activity and safety of cabozantinib (cabo) plus atezolizumab (atezo) in different endocrine neoplasms refractory to standard therapies.
Methods
This is a prospective, multi-center, open-label, phase II study including patients (pts) with advanced and refractory endocrine tumors in 6 independent cohorts (C): (1) well-differentiated neuroendocrine tumors of the lung (LungNET), (2) anaplastic thyroid cancer (ATC), (3) adrenocortical carcinoma (ACC), (4) pheochromocytoma/ paraganglioma (PPGL), (5) well-differentiated gastroenteropancreatic NET (GEPNET), (6) grade 3 extrapulmonary neuroendocrine neoplasms (G3 EP-NEN). All pts received atezo 1200 mg IV Q3W plus cabo 40 mg/day PO until progression or unacceptable toxicity. The primary endpoint was Overall Response Rate (ORR) by RECIST 1.1. With a Simon II stage design, 1 response of 9 pts/C were needed at 1st stage to continue accrual in 2nd stage. C1 and C6 did not pass 1st stage, and C2 and C4 were closed due to slow accrual.
Results
93 pts were enrolled. Cabo and atezo were administered for a median of 5.8 m (95% CI: 3.4-7.5) and 6.3 m (95% CI: 3.5-7.7), respectively. Most frequent grade ≥3 toxicities were fatigue (7.5%), neutropenia (6.5%) and liver enzyme increase (6.5%). 2 pts died due to drug-related ischemic stroke and pancreatitis. Due to AE’s, cabo and atezo treatment was interrupted in 67.7% and 35.5% of pts, and discontinued in 16.1% and 14% of pts, respectively. Cabo was reduced to 20 mg/day in 41.9% of pts. Survival was similar regardless of cabo reduction.
Table: 723O
LungNET | ATC | ACC | PPGL | GEPNET | G3 EP-NEN | |
N | 9 | 14 | 24 | 13 | 24 | 9 |
ORR (%) | 0 | 21.4 | 8.3 | 7.7 | 16.7 | 0 |
median PFS (m [95% CI]) | 8.4 [7.7-NR] | 4.1 [2.7-NR] | 2.9 [2.8-5.7] | 8.6 [5.7-NR] | 13 [11.2-NR] | 2.7 [2.6-NR] |
Conclusions
Cabo plus atezo showed limited activity in progressive / refractory endocrine malignancies, surpassing the futility threshold in ATC. Atezo does not improve the outcomes of cabo as a single agent in NEN.
Clinical trial identification
EudraCT 2019-002279-32; NCT04400474.
Editorial acknowledgement
We acknowledge MFAR Clinical Research staff for their assistance in the development of this abstract.
Legal entity responsible for the study
Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).
Funding
GETNE through industry partners Ipsen and Roche.
Disclosure
R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, BMS, HMP, Ipsen, Merck, Midatech, MSD, Novartis, Pharma Mar, Pierre Fabre, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Global PI of investigator-initiated clinical trials (AXINET, NICENEC, PEMBROLA): BMS, MSD, Pfizer; Other, Honoraria received by spouse for advisory board or invited speaker roles: Abbvie, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Genomica, Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. C. López: Financial Interests, Personal, Invited Speaker: AAA, Amgen, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Merk, Novartis, Pfizer, Roche, Servier; Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Eisai, Ipsen, Lilly, Merk, Pfizer, Roche, Servier; Financial Interests, Personal and Institutional, Research Grant: Amgen, AstraZeneca; Financial Interests, Personal, Funding: Bayer, Eisai, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Coordinating PI: Eisai, Ipsen; Financial Interests, Personal, Steering Committee Member: Ipsen; Financial Interests, Personal, Local PI: Ipsen, Roche; Financial Interests, Personal, Research Grant: Servier. C. Hierro: Financial Interests, Personal, Invited Speaker: MSD, Lilly; Financial Interests, Personal, Research Grant, Principal Investigator of Merk sponsored trial: Merk; Non-Financial Interests, Principal Investigator, Clinical Trial: BMS, Zymeworks, ALX Oncology, AstraZeneca; Other, Travel fees: BMS, Amgen, Roche, Merck. M. Llanos: Financial Interests, Personal, Speaker, Consultant, Advisor: Ipsen, Amgen, Servier, AAA, Eisai, Roche, Merck, Lilly, Bristol, Sanofi. E. Grande: Financial Interests, Personal, Invited Speaker: Adacap, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, Ipsen, Janssen, Lilly, Merck KGa, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, ONCODNA (Biosequence); Non-Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche; Non-Financial Interests, Institutional, Coordinating PI: Ipsen; Non-Financial Interests, Personal, Other, AD Board member: Enets. All other authors have declared no conflicts of interest.
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