Abstract 559P
Background
Somatic HER2 mutations are oncogenic drivers in 3–6% of CC. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor, has demonstrated single-agent activity in multiple HER2-mutant cancers [Hyman et al. Nature 2018], including HER2-mutant R/M CC [Oaknin et al. doi.org/10.1016/j.ygyno.2020.07.025]. We describe updated findings from the HER2-mutant R/M CC cohort from SUMMIT (cut-off date: Mar 18, 2022).
Methods
Patients (pts) with R/M CC and HER2 mutations documented by local testing received oral neratinib 240 mg once daily with up to 2 cycles of mandatory loperamide prophylaxis. Tumor response was assessed by investigators using RECIST 1.1 and/or PET Response Criteria. Endpoints: confirmed objective response rate (ORR); duration of response; clinical benefit rate (CBR); progression-free survival (PFS); safety. Clinicaltrials.gov: NCT01953926.
Results
As of Mar 18, 2022, 22 pts with HER2-mutant R/M CC were enrolled (adenocarcinoma, 82%; squamous cell carcinoma, 18%). Single HER2 mutations: S310F/Y (n=10); R678Q (n=2); D769H/N (n=2); other (n=4). Four pts had 2 HER2 mutations, 3 of which included S310F/Y. Prior treatments included platinum-based chemotherapy (100%), bevacizumab (73%), and pembrolizumab (18%). Median duration of neratinib therapy was 3.7 months (range 0.5–64.7 months). Efficacy results (efficacy evaluable population) are shown in the Table. ORR was 18% (95% CI 5–40%) and CBR was 46% (95% CI 24–68%). Median PFS was 5.1 months (95% CI 1.7–7.2 months). Prior treatment with bevacizumab did not appear to influence outcomes. Diarrhea was the most commonly reported adverse event (all grade, 90.9%; grade 1, 31.8%; grade 2, 36.4%, grade 3, 23%; grade 4, 0%). No patients discontinued treatment due to diarrhea. Table: 559P
| Endpoint | Prior bevacizumab | Total (N=22) | |
| Yes (n=16) | No (n=6) | ||
| Confirmed objective response, n (%) | 3 (19) | 1 (17) | 4 (18) |
| CR | 1 (6) | 0 | 1 (5) |
| PR | 2 (13) | 1 (17) | 3 (14) |
| ORR, % (95% CI) | 19 (4–46) | 17 (0–64) | 18 (5–40) |
| Median DoR, months (95% CI) | 5.9 (5.6–9.3) | 12.3 (NE) | 7.6 (5.6–12.3) |
| Clinical benefit, n (%) | 7 (44) | 3 (50) | 10 (46) |
| CR | 1 (6) | 0 | 1 (5) |
| PR | 2 (13) | 1 (17) | 3 (14) |
| SD (≥16 weeks) | 4 (25) | 2 (33) | 6 (27) |
| Clinical benefit rate, % (95% CI) | 44 (20–70) | 50 (12–88) | 46 (24–68) |
| Median PFS, months (95% CI) | 4.4 (1.7–7.2) | 5.5 (1.7–20.1) | 5.1 (1.7–7.2) |
CBR, CR + PR + SD ≥16 weeks; CR, complete response; DoR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease
Conclusions
These encouraging results support the clinical benefit of neratinib in this patient population and warrant further investigation following platinum failure.
Clinical trial identification
NCT01953926.
Editorial acknowledgement
Lee Miller, Miller Medical Communications Ltd., provided editorial/writing assistance for this abstract.
Legal entity responsible for the study
Puma Biotechnology, Inc.
Funding
Puma Biotechnology, Inc.
Disclosure
C.F. Friedman: Non-Financial Interests, Personal, Advisory Board: Merck, Genentech; Financial Interests, Personal, Other, Consultant: Seagen, BMS. A.V. Tinker: Financial Interests, Personal and Institutional, Advisory Board: AztraZeneca; Financial Interests, Personal and Institutional, Funding: AztraZeneca; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Advisory Board: GSK, Eisai, Viatris. J.W. Goldman: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech, Eli Lilly, Janssen, AbbVie; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Genentech, Eli Lilly, Janssen, BMS, AbbVie. S. Loi: Financial Interests, Institutional, Research Grant: Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca, Roche-Genentech, Seattle Genetics; Financial Interests, Institutional, Other, Consultant: Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, AstraZeneca, Silverback Therapeutics, G1 Therapeutics, Puma Biotechnologies, Pfizer, Gilead Therapeutics, Seattle Genetics, Daiichi Sankyo, Merck, Amunix, Tallac Therapeutics, Eli Lilly, Bristol Meyers Squibb. M. Melisko: Financial Interests, Institutional, Research Grant, PI on Clinical Trial: Novartis, KCRN, Puma Biotechnology. A. Oaknin: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Deciphera Pharmaceuticals, Genmab, GSK, ImmunoGen, Mersana Therapeutics, PharmaMar, Roche, Tesaro, Merck Sharps & Dohme de España, SA, Agenus, Sutro, Corcept Therapeutics, EMD Serono, Novocure, prIME Oncology, Sattucklabs, Itheos, Eisai, F. Hoffmann-La Roche,; Financial Interests, Personal, Other, Travel and accomodation: AstraZeneca, PharmaMar, Roche; Financial Interests, Institutional, Funding: Abbvie Deutschland, Advaxis Inc., Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Clovis Oncology Inc, EISAI limited LTD, F. Hoffmann –La Roche LTD, Regeneron Pharmaceuticals, ImmunoGen Inc, Merck, Sharp & Dohme de España SA, Millennium Pharmaceuticals Inc, PharmaMar SA, Tesaro Inc., Bristol Myers Squibb; Non-Financial Interests, Leadership Role, Executive Board member as a Co-Chair: GEICO; Non-Financial Interests, Leadership Role, Phase II Committee and Cervix Cancer Committee Representative on behalf of GEICO: GCIG; Non-Financial Interests, Officer, Chair of Gynaecological Track ESMO 2019. Scientific Track Member Gynaecological Cancers ESMO 2018, ESMO 2020, ESMO 2022. Member of Gynaecological Cancers Faculty and Subject Editor Gyn ESMO Guidelines.: ESMO; Non-Financial Interests, Member: ESMO, ASCO, GCIG, SEOM, GOG. I. Spanggaard: Financial Interests, Institutional, Principal Investigator: Roche, Puma Biotechnology, MSD, Genentech, Incyte, AstraZeneca, Orion, Pfizer; Financial Interests, Institutional, Research Grant: Genmab, Bristol-Myers Squibb, Loxo/Bayer, Loxo/Lilly, Novartis. A.L. Frazier: Financial Interests, Personal, Full or part-time Employment: Puma Biotechnology, Inc.; Financial Interests, Personal, Stocks/Shares: Puma Biotechnology, Inc. B. Zhang: Financial Interests, Personal, Full or part-time Employment: Puma Biotechnology, Inc.; Financial Interests, Personal, Stocks/Shares: Puma Biotechnology, Inc. L.D. Eli: Financial Interests, Personal, Full or part-time Employment: Puma Biotechnology, Inc.; Financial Interests, Personal, Stocks/Shares: Puma Biotechnology, Inc. D.B. Solit: Financial Interests, Personal, Advisory Board: Pfizer, Loxo/Lilly Oncology, Scorpion Therapeutics, Vividion Therapeutics, FORE Therapeutics, BridgeBio; Financial Interests, Personal, Stocks/Shares: Scorpion Therapeutics, Vividion Therapeutics, FORE Therapeutics. All other authors have declared no conflicts of interest.