490MO - Patient-reported outcomes of first-line selpercatinib versus chemotherapy with or without pembrolizumab in RET fusion-positive advanced non-small cell lung cancer: Interim analysis of LIBRETTO-431

Background

Selpercatinib, a highly selective and potent CNS penetrant RET inhibitor has been approved for treatment of advanced RET fusion+ non-small-cell lung cancer (NSCLC). LIBRETTO-431 (NCT04194944), is a randomized, phase 3 trial comparing first-line selpercatinib to platinum-based chemotherapy +/- pembrolizumab (pembro). This analysis describes the patient-reported outcomes (PROs) from LIBRETTO-431.

Methods

PRO data (data cut-off: 01 May 2023) were evaluated for the intent-to-treat (ITT) population and the subgroup of patients that received pembro (ITT-pembro). Time to confirmed deterioration (TTCD) of pulmonary symptoms (using NSCLC-Symptom Assessment Questionnaire [SAQ]) and physical function (using EORTC QLQ-C30 Physical Function scale [QLQ-C30 PF]) was time from randomization to the first ≥2 point increase of NSCLC-SAQ total score or ≥5 point decrease in QLQ-C30 PF, confirmed at next assessment. TTCD was compared between treatment groups using log rank test and Cox proportional hazards model. Symptomatic adverse events (using PRO version of the CTCAE item library) were reported descriptively as baseline-adjusted worst score. PROs were also analyzed for East Asia vs. non-East Asia subgroups.

Results

In ITT-pembro (selpercatinib n=129 and control n=83), selpercatinib delayed TTCD of pulmonary symptoms (hazard ratio [HR]=0.34, 95% CI: 0.20-0.55) and physical function (HR=0.54, 95% CI: 0.39-0.75). Patients in the selpercatinib arm reported worse PRO-CTCAE scores of dry mouth, diarrhea, and arm/leg swelling, whereas those in the control arm reported worse scores of nausea, fatigue, and decreased appetite. Results were consistent in the ITT population. PROs were similar between East Asia and non-East Asia subgroups.

Conclusions

PRO data were consistent with the favorable efficacy of selpercatinib compared with platinum-based chemotherapy +/- pembro. Selpercatinib significantly delayed TTCD of pulmonary symptoms and physical function and was well-tolerated in these patient populations.

Clinical trial identification

NCT04194944.

Editorial acknowledgement

Keerthana Muthiah, Eli Lilly and Company.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co., Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Taiho Pharmaceutical Co., Ltd., Syneos Health Clinical K.K., Life Technologies Japan Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K., Medpace Japan K.K., Haihe Biopharma Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., KISSEI Pharmaceutical CO., LTD., Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical&Biological Laboratoires Co., LTD., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Craif Inc., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K., Pfizer R&D Japan G.K., Turning Point Therapeutics,Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. S. Novello: Financial Interests, Personal, Invited Speaker: AZ, MSD, Eli Lilly, Novartis, BeiGene, Amgen; Financial Interests, Personal, Advisory Board: BI, BMS, Pfizer, Takeda, Roche, Sanofi, Amgen; Financial Interests, Institutional, Coordinating PI, IIT: MSD, BI; Non-Financial Interests, Personal, Leadership Role, president of this european advocacy: WALCE. P. Garrido Lopez: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BMS, GSK, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Sanofi, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Advisory Board, Spouse: Boehringer Ingelheim, Gebro, Janssen, Nordic; Financial Interests, Personal, Invited Speaker, Spouse: Boehringer Ingelheim, Janssen; Financial Interests, Personal, Other, Data monitoring committee for INC280I12201 trial in 2020: Novartis; Financial Interests, Personal, Steering Committee Member, CACZ885V2201C_CANOPY-N trial: Novartis; Financial Interests, Personal, Other, Lung Cancer Medical Education TASC Committee 2021: Janssen; Financial Interests, Institutional, Local PI: Novartis, Janssen, AstraZeneca, Pfizer, Blue print, Apollomics, Amgen, Array Biopharma; Financial Interests, Personal, Steering Committee Member, IO102-012/KN-764 trial: IO Biotech; Financial Interests, Personal, Steering Committee Member, JNJ-61186372 (JNJ-372) Clinical Development Program: Janssen; Non-Financial Interests, Personal, Leadership Role, Council member as Women for Oncology Committee ChairFellowship and Award Committee and Press CommitteeFaculty for lung and other thoracic tumours: ESMO; Non-Financial Interests, Personal, Leadership Role, President of the Spanish Federation of Medical Societies (FACME) 2020-2022Past President 2023-2024: FACME; Non-Financial Interests, Personal, Leadership Role, Former President of Spanish Medical Oncology Society: SEOM; Non-Financial Interests, Personal, Leadership Role, Member of the Scientific Committee of the Spanish Against Cancer Research Foundation (aecc) and also Board member: AECC; Non-Financial Interests, Personal, Leadership Role, IASLC Women in Thoracic Oncology Working Group Member: IASLC; Non-Financial Interests, Personal, Advisory Role, Member of the Spanish National Health Advisory Board: Spanish Minister of Health; Non-Financial Interests, Personal, Advisory Role, Assesmment for lung cancer screening evaluation: EUnetHTA,; Non-Financial Interests, Personal, Advisory Role: Spanish National Evaluation network (RedETS); Non-Financial Interests, Personal, Advisory Role, scientific advisory group member for clinical immunological, oncology and lung cancer areas: EMA; Other, Personal, Other, My son is working in the pharma company TEVA as an engineer. I do not have any kind of relationship with TEVA: TEVA. J.A. Alatorre Alexander: Financial Interests, Personal, Funding, Payments Done to Health Pharma Professional Reseach: Eli Lilly and Company; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting fees: BMS; Financial Interests, Personal, Other, Support for attending meetings and/or travel: MSD, AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: BMS, MSD, AstraZeneca, TAKEDA, Roche, Amgen, Janssen, ASO PHARMA. N. Reinmuth: Financial Interests, Personal, Invited Speaker, including Ad-Boards: AstraZeneca; Financial Interests, Personal, Invited Speaker: Amgen, Lilly, Pfizer, Takeda, Merck, Hoffmann-La Roche, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker, including Advisory Boards: Bristol Myers Squibb, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Invited Speaker: Sanofi. A. Gilligan: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. N. Payakachat: Financial Interests, Personal, Full or part-time Employment: Eli Lilly and Company. C. Zhou: Financial Interests, Personal, Invited Speaker, Honoraria: Eli Lily, Roche, Sanofi, Qilu Pharma, Hengrui, Innovent Biologics, C-Stone, LUYE Pharma, TopAlliance Biosciences Inc; Financial Interests, Personal, Invited Speaker, BI: BI; Financial Interests, Personal, Invited Speaker, MSD: MSD; Financial Interests, Personal, Advisory Board, Advisor: Amoy Diagnositics. All other authors have declared no conflicts of interest.