Health-related quality of life associated with trifluridine/tipiracil in combination with bevacizumab in refractory metastatic colorectal cancer: An analysis of the phase 3 SUNLIGHT trial

The SUNLIGHT trial, an international, open-label, randomised, phase 3 study comparing trifluridine/tipiracil (FTD/TPI) plus bevacizumab (bev) to FTD/TPI monotherapy in patients with refractory metastatic colorectal cancer (mCRC), demonstrated that the combination of FTD/TPI + bev significantly improved overall survival (OS) and progression-free survival (PFS) with a predictable and manageable safety profile. The median OS was improved by 3.3 months with FTD/TPI + bev (10.8 months with FTD/TPI + bev vs. 7.5 months with FTD/TPI), hazard ratio of 0.61 (95% CI, 0.49 to 0.77; P < 0.001). Median PFS in the FTD/TPI + bev group was of 5.6 months vs. 2.4 months in the FTD/TPI group (hazard ratio, 0.44; 95% CI, 0.36 to 0.54; P < 0.001). Here, we report health-related quality of Life (HRQoL) outcomes.

HRQoL was evaluated at baseline, at each cycle, and at withdrawal visit using EORTC QLQ-C30 and EQ-5D-5L questionnaires. QoL outcomes were defined as mean changes from baseline in QLQ-C30 domains (at least 10 points were considered as the minimal important difference) and time to deterioration. Post-hoc analyses assessing the time to definitive worsening of EQ-5D-5L utility score and visual analog scale (VAS) by more than 0.08 and 7 points respectively, are reported.

Among the 492 randomized patients, 239 and 241 (>97%) had QoL data at baseline in the combination and monotherapy arms, respectively. The cut-off point for the analysis was 12 cycles for FTD/TPI + bev and 6 cycles for FTD/TPI monotherapy owing that higher number of cycles were associated with a lower completion rate ( < 10%) not allowing us a meaningful interpretation. For both questionnaires, mean baseline scores were similar throughout the treatment and showed a comparable HRQoL scores with no clinically relevant changes over time. Patients treated with FTD/TPI + bev or with FTD/TPI monotherapy, did not show increased symptom burden as assessed by the QLQ-C30 symptom domains. Patients receiving FTD/TPI plus bevacizumab had a reduced risk of global health status (GHS) definitive worsening of more than 10 points (median time to worsening in GHS was 8.54 months in the FTD/TPI + bev arm vs. 4.7 months in the FTD/TPI arm [hazard ratio, 0.50; 95% CI, 0.38 to 0.65]) and in all scales and subscales. In a sensitivity analysis considering disease progression and death as a definitive deterioration measured by QLQ-C30, HRQoL deteriorated significantly later (median GHS in the FTD/TPI + bev group was of 4.5 months vs. 2.07 months in the FTD/TPI group (hazard ratio, 0.49; 95% CI, 0.40 to 0.60), consistently favoring the combination arm. A similar result was observed with the EQ-5D-5L utility score and VAS showing that patients treated with the combination were less likely to deteriorate before those treated with FTD/TPI monotherapy.

QoL was maintained in both arms with a trend toward a prolonged time to definitive deterioration of HRQoL scales and subscales in FTD/TPI + bev as compared to FTD/TPI monotherapy.

NCT04737187.

Institut de Recherches Internationales Servier and Taiho Oncology, Inc.

The study was sponsored by Institut de Recherches Internationales Servier and and Taiho Oncology, Inc.

G. Prager: Advisory / Consultancy: Merck, Roche, Amgen , Sanofi, Lilly, Bayer, Servier, CECOG, MSD, BMS, Pierre Fabre, Incyte, Novartis; AstraZeneca. J. Taieb: Honoraria (self): servier; Advisory / Consultancy: servier; Speaker Bureau / Expert testimony: servier. M. Fakih: Honoraria (self): Guardant Health, Incyte; Advisory / Consultancy: Incyte, Seattle Genetic, GSK; Research grant / Funding (institution): Verastem, Amgen, BMS. E. Van Cutsem: Advisory / Consultancy: Array BioPharma, Astellas Pharma, Astrazeneca, Bayer, Biocartis, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, GSK, Halozyme, Incyte, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis,Pierre Fabre, Roche, SERVIER, Sirtex Medical, Taiho Pharmaceutical; Research grant / Funding (institution): Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier . E. Elez: Honoraria (self): Amgen, Bayer, Hoffman La - Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, Seagen, Servier.; Advisory / Consultancy: Amgen, Bayer, Hoffman La - Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, Seagen, Servier.; Speaker Bureau / Expert testimony: Novartis, Organon; Research grant / Funding (institution): Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc.; Travel / Accommodation / Expenses: Amgen, Bayer, Hoffman La - Roche, Merck Serono, MSD, Novartis, Organon, Pierre Fabre, Sanofi, Seagen, Servier.; Non-remunerated activity/iesA: American Society of Clinical Oncology (ASCO), Volunteer member of the ASCO Annual Meeting Scientific Program Committee: Developmental Therapeutics – Immunotherapy. European Society for Medical Oncology (ESMO), Speaker of the ESMO Academy. Sociedad Española de Oncología Médica (SEOM), Coordinator of the SEOM +MIR Section of Residents and Young Assistants. P. Poureau: Speaker Bureau / Expert testimony: BAYER, ROCHE; Research grant / Funding (institution): SERVIER; Travel / Accommodation / Expenses: IPSEN, SERVIER. D. Modest: Honoraria (self): Amgen, Merck, Roche, BMS, MSD, Pierrefabre; Servier, AstraZeneca, Sanofi, Takeda, GSK, Seagen, Onkowissen, G1, Transgene, Incyte; Research grant / Funding (institution): Servier , Amgen; Travel / Accommodation / Expenses: Amgen, Servier. H. Hassan: Full / Part-time employment: Institut de Rercherches Internationales Servier. D. Skanji: Honoraria (Institution): SERVIER. J. Tabernero: Honoraria (self): educational collaboration with Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER); Advisory / Consultancy: scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Cardiff Oncology, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, TheraMyc and Tolremo Therapeutics; Research grant / Funding (institution): institutional financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK.; Shareholder / Stockholder / Stock options: Oniria Therapeutics. All other authors have declared no conflicts of interest.