Validation of prognostic scoring systems for patients with metastatic renal cell carcinoma enrolled in phase I clinical trials.

BACKGROUND

For patients with metastatic renal cell carcinoma (mRCC) who progress on standard-of-care therapies, there is an unmet need for novel treatments. Phase I clinical trials are designed to test the safety, toxicity and optimal dosing of novel agents. Herein, we analysed the outcomes of patients with mRCC enrolled in phase I trials and assess the utility of prognostic scores.

METHODS

Patients with all histologies of mRCC were included if they received treatment on a phase I clinical trial at MD Anderson Cancer Center (MDACC). Survival outcomes were calculated using Cox proportional hazard model. Prognostic value of the International Metastatic RCC Database Consortium (IMDC), Royal Marsden Hospital (RMH) and MDACC scores was assessed using the likelihood ratio (LR) χ

RESULTS

Among 82 patients with mRCC who received treatment, 21 patients participated in more than one trial, resulting in 106 trial participants (TP). Median prior therapies was two. For all TPs, median overall survival (OS) was 31.2 months, progression-free survival (PFS) was 5.9 months and objective response rate was 22%. Median OS and PFS were significantly shorter with increasing IMDC, RMH and MDACC scores. The RMH and MDACC scores outperformed the IMDC score for predicting OS (RMH LR χ

CONCLUSIONS

The RMH and MDACC prognostic scores can be used to predict OS for patients with mRCC in phase I trials and may guide patient selection. Patients with mRCC should be considered for phase I trials.

Informations de copyright

© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.

Déclaration de conflit d'intérêts

Competing interests: AWH, OA, EC, HL and JR have no conflicts to disclose. PM reports consultancy/honoraria to Pfizer, Bristol-Myers Squibb, Mirati, Exelixis and Axiom Healthcare Strategies; research funding to his institution from Mirati, Takeda, Bristol-Myers Squibb and Gateway for Cancer Research. FM-B reports consulting to Aduro BioTech, DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche, Genentech, IBM Watson, Jackson Laboratory, Kolon Life Science, OrigiMed, PACT Pharma, Parexel International, Pfizer, Samsung Bioepis, Seattle Genetics, Tyra Biosciences, Xencor and Zymeworks. She reports honoraria from Chugai Biopharmaceuticals, Mayo Clinic and Rutgers Cancer Institute of New Jersey. She reports research funding to her institution from Aileron Therapeutics AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences, Curis, CytomX Therapeutics, Daiichi Sankyo, Debiopharm International, eFFECTOR Therapeutics, Genentech, Guardant Health, Millennium Pharmaceuticals, Novartis, Puma Biotechnology and Taiho Pharmaceutical. AN reports consulting to CytomX Therapeutics, Novartis, Kymab and Genome. He reports travel and accommodation expenses from ARMO BioSciences. He reports research funding to his institution from NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor, Amplimmune, ARMO BioSciences, Eli Lilly, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Kymab, PsiOxus and Immune Deficiency Foundation (Spouse). EJ reports research funding to his institution from Exelixis, Merck and Pfizer. He reports consulting for Eisai, Exelixis, Novartis, Merck, Pfizer, Roche. Sarina Piha-Paul reports research funding to her institution from AbbVie, ABM therapeutics, Acepodia, Alkermes, Aminex Therapeutics, Amphivena Therapeutics, BioMarin Pharmaceutical, Boehringer Ingelheim, Bristol Myers Squib, Chugai Pharmaceutical, Daichi Sankyo, Eli Lilly, Five Prime Therapeutics, Genmab A/S, GlaxoSmithKline, Helix BioPharma, Incyte, Jacobio Pharmaceuticals, Medimmune, Medivation, Merck Sharp and Dohme, Novartis Pharmaceuticals, Pieris Pharmaceuticals, Pfizer, Principia Biopharma, Puma Biotechnology, Rapt Therapeutics, Seattle Genetics, Taiho Oncology, Tesaro and TransThera Bio. NMT reports consultancy and honoraria from Pfizer, Novartis, Bristol-Myers Squibb, Exelixis, Nektar, Eisai, Ono Pharmaceutical, Eli Lilly, Oncorena, Ipsen, Surface Oncology and Neolukin Therapeutics. He reports research funding to his institution from Bristol-Myers Squibb, Exelixis, Pfizer, Nektar Therapeutics, Calithera Bioscience, Eli Lilly, Mirati Therapeutics, Arrowhead Pharmaceuticals, Takeda, Epizyme and Eisai. He reports travel expenses from Pfizer, Novartis, Nektar, Bristol-Myers Squibb, Eisai, Onco Pharmaceuticals, Oncorena, Surface Oncology, Lilly Oncology, Ipsen, and Neolukin Therapeutics. David S. Hong reports research funding to his institution from AbbVie, Adaptimmune, Aldi-Norte, Amgen, Astra-Zeneca, Bayer, BMS, Daiichi-Sankyo, Eisai, Fate Therapeutics, Genentech, Genmab, GSK, Ignyta, Infinity, Kite, Kyowa, Lilly, LOXO, Merck, MedImmune, Mirati, miRNA, Molecular Templates, Mologen, NCI-CTEP, Novartis, Pfizer, Seattle Genetics, Takeda, and Turning Point Therapeutics. He reports travel expenses from Bayer, LOXO, miRNA, Genmab, AACR, ASCO, and SITC. He reports consulting for Alpha Insights, Amgen, Axiom, Adaptimmune, Baxter, Bayer, Genentech, GLG, Group H, Guidepoint, Infinity, Janssen, Merrimack, Medscape, Numab, Pfizer, Prime Oncology, Seattle Genetics, Takeda, Trieza Therapeutics, and WebMD. He reports ownership interests in Molecular Match (Advisor), OncoResponse (Founder), Presagia Inc (Advisor). Shubham Pant reports research funding to his institution from Mirati Therapeutics, Eli Lilly, Red Hill Biopharma Ltd., Xencor, Five Prime Therapeutics, Novartis, Rgenix, Sanofi-Aventis, Arqule, Bristol-Myers Squibb, Onco Response, Sanofi US Services Inc., and GlaxoSmithKline. Timothy Yap reports research funding to his institution from: AstraZeneca, Bayer, Clovis, Constellation, Cyteir, Eli Lilly, EMD Serono, Forbius/Formation Biologics, F-Star, GlaxoSmithKline, Genentech, ImmuneSensor, Ipsen, Jounce, Karyopharm, Kyowa, Novartis, Pfizer, Ribon Therapeutics, Regeneron, Sanofi, Seattle Genetics, Tesaro, and Vertex Pharmaceuticals. He reports consultancy from Almac, Aduro, AstraZeneca, Atrin, Axiom, Bayer, Calithera, Clovis, Cybrexa, EMD Serono, F-Star, Guidepoint, Ignyta, I-Mab, Jansen, Kyn Therapeutics, Merck, Pfizer, Roche, Seattle Genetics, and Zai Labs.Vivek Subbiah reports research funding to his institution from LOXO Oncology, Roche/Genentech, Novartis, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, Pharmamar, D3, Pfizer, Amgen, Multivir, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exelixis, Blueprint Medicines, Medimmune, Altum, Dragonfly Therapeutics, Takeda, National Comprehensive Cancer Network, Turning Point Therapeutics, and Boston Pharmaceuticals. He reports consultancy for Helsinn, Incyte, and QED Pharma. He reports travel expenses from Helsinn, Incyte, ASCO and ESMO.