INTRODUCTION: Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown. METHODS: A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021. RESULTS: Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases (n = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade
- Illini, O.
- Hochmair, M. J.
- Fabikan, H.
- Weinlinger, C.
- Tufman, A.
- Swalduz, A.
- Lamberg, K.
- Hashemi, S. M. S.
- Huemer, F.
- Vikström, A.
- Wermke, M.
- Absenger, G.
- Addeo, A.
- Banerji, S.
- Calles, A.
- Clarke, S.
- Di Maio, M.
- Durand, A.
- Duruisseaux, M.
- Itchins, M.
- Kääränien, O. S.
- Krenn, F.
- Laack, E.
- de Langen, A. J.
- Mohorcic, K.
- Pall, G.
- Passaro, A.
- Prager, G.
- Rittmeyer, A.
- Rothenstein, J.
- Schumacher, M.
- Wöll, E.
- Valipour, A.
Keywords
- RET gene fusions
- non-small cell lung cancer (NSCLC)
- real-world data
- selpercatinib
- targeted therapy
- tyrosine kinase inhibitor (TKI)
- honoraria for advisory boards from Boehringer Ingelheim, Eli Lilly, Menarini, Merck
- Sharp & Dohme, Pfizer, and Roche. Maximilian Johannes Hochmair, Honoraria from
- AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme,
- Pfizer, and Roche, and has had consulting or advisory roles with Boehringer
- Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, and Roche. Hannah Fabikan, Speaker
- fee from Roche. Christoph Weinlinger, No conflict of interest. Amanda Tufman,
- Advisory Boards: Lilly, Pfizer, MSD, BMS, GSK, Celgene, Roche, Takeda, Boehringer
- Ingelheim, Amgen, AstraZeneca. Projects financed by AstraZeneca und Takeda. Aurélie
- Swalduz, Roche, Bristol-Myers Squibb, Takeda, Lilly, Pfizer, AstraZeneca,
- Boehringer-Ingelheim. Kristina Lamberg, Advisory boards: MSD and AstraZeneca. Sayed
- M.S. Hashemi, Advisory board/research grants: Abbvie, AstraZeneca, BMS, Boehringer
- Ingelheim, Eli Lilly, GSK, MSD, Novartis, Roche, Takeda, Xcovery. Florian Huemer,
- Advisory Boards and Honoraria: MSD, BMS, Roche, Sanofi, Lilly, Takeda, Astra Zeneca,
- Boehringer Ingelheim. Anders Vikström, Ad-boards: AstraZeneca, Abbvie, BMS,
- Boehringer-Ingelheim, Pfizer, Roche, Takeda. Lectures: AstraZeneca, BMS,
- Boehringer-Ingelheim, MSD, Roche, Takeda. Grants: Boehringer-Ingelheim
- Consultancies: Astra Zeneca, Boehringer-Ingelheim, Roche. Martin Wermke, Received
- speaker fees and/or honoraria for advisory boards from BMS, Merck, Roche, Novartis,
- Kite, Boehringer Ingelheim, Astra Zeneca, Heidelberg Pharma. Gudrun Absenger,
- Honoraria from: AMGEN, AstraZeneca, BMS, Böhringer Ingelheim, Lilly, MSD, Novartis,
- Pfizer, Roche, Sanofi, Takeda. Alfredo Addeo, Personal fees from Bristol-Myers
- Squibb, AstraZeneca, Roche, Pfizer, Merck Sharp and Dohme, and Boehringer-Ingelheim
- for work performed outside of the current study. Shantanu Banerji, Honoraria for
- advisory board: AstraZeneca, Bayer, BMS, EMD-Serono, Merck, Novartis, Pfizer, Roche,
- Takeda Speaker Fees: None Research Funds: AstraZeneca. Antonio Calles,
- Honoraria/consulting fees from AstraZeneca, Boehringer-Ingelheim, Pfizer,
- Roche/Genentech, Eli Lilly and Company, Takeda, Novartis, Merck Sharp & Dohme, and
- Bristol-Myers Squibb
- Research grants from MSD and PharmaMar. Stephen Clarke,
- Advisory board and speaking remuneration from AstraZeneca. Massimo Di Maio,
- Honoraria and had roles as consultant or advisor for AstraZeneca, Pfizer, Novartis,
- Roche, Takeda, Eisai, Janssen, Astellas
- received institutional research grant by
- Tesaro – GlaxoSmithKline. Alice Durand, No conflict of interest. Michaël
- Duruisseaux, Membership of an advisory council or committee for Roche, BMS, MSD,
- AstraZeneca, Abbvie, Takeda, Boehringer Ingelheim, Merus, Amgen and Pfizer
- consulting fees from Roche, BMS, MSD, AstraZeneca, Abbvie, Takeda, Boehringer
- Ingelheim, and Pfizer
- research grants from Takeda, NanoString, and Blueprint.
- Malinda Itchins, AdBoard: Pfizer, Takeda. Consultancy: Roche, Merck. Honoraria: AZ,
- Pfizer, takeda, Roche, Novartis. Academic travel support: Roche, MSD. Okko-Sakari
- Kääränien, No conflict of interest associated with this study. Florian Krenn,
- Advisory Boards: Roche, MSD. Eckart Laack, Honoraria for advisory boards:
- AstraZeneca, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD, Novartis, Lilly.
- Speaker fees. AstraZeneca, BMS, Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD,
- Novartis, Lilly. Research grants and clinical study: AstraZeneca, BMS,
- Boehringer-Ingelheim, Pfizer, Roche, Takeda, MSD, Novartis, Lilly. Adrianus Johannes
- de Langen, Research grants: BMS, MSD, AstraZeneca, Boehringer, Merus Non-financial
- support: Merck, Roche Advisory boards: Lilly, Bayer, MSD, AstraZeneca. Katja
- Mohorcic, Honoraria for ad-boards and speaker from MSD, Pfizer, Roche, AstraZeneca,
- Boehringer Ingelheim, BMS, Abbvie. Georg Pall, Speakers honoraria and advisory
- board-member: Eli Lilly, Roche. Antonio Passaro, Honoraria for consulting, advisory
- role or lectures from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli
- Lilly, Janssen, Merck Sharp & Dohme, Pfizer and Roche Genentech. Gerald Prager,
- Advisory Board Meetings/Symposiums: Merck, Roche, Amgen, Sanofi, Lilly, Servier,
- Taiho, Bayer, BMS, MSD, Celgene, Pierre Fabre, Terumo. Achim Rittmeyer, Grants as an
- advisor or speaker: AbbVie, Astra Zeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD,
- Novartis, Pfizer and Roche. Jeffrey Rothenstein, Advisory Boards: Amgen, AZ, BMS,
- Merck, Pfizer, Roche. Michael Schumacher, Consulting, speakers fee, advisory panel
- membership, travel grants: AstraZeneca, Pfizer, Boehringer Ingelheim, Takeda, Roche,
- Amgen, Eli Lilly, MSD, BMS, Novartis. Ewald Wöll, Advisory boards or speaker fees:
- Amgen, Astra Zeneca, BMS, Celgen, Ebewe, Eli Lilly, Eisai, Janssen Cilag, Merck,
- MSD, Pierre Fabre, Pfizer, Ratiopharm, Roche, Sanofi Aventis. Arschang Valipour,
- Personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini, Merck,
- Novartis, and Roche for lectures and/or advisory boards outside of the submitted
- study.
