Abstract 779P
Background
Enrolling patients with advanced, relapsed, or refractory bladder cancers in phase I trials of novel therapies may yield some unique insight into previously unexplored therapeutic targets, provide an opportunity to identify signals of early treatment response in these patients, and benefit these patients clinically. Prognostic scores could be helpful in selecting patients for referral to these trials.
Methods
We retrospectively analyzed medical records of patients with mBC who received an investigational therapy at the phase 1 clinic at MD Anderson. The Bellmunt score (hemoglobin, liver metastases, Eastern Cooperative Oncology Group performance status [ECOG PS]) was used as an mBC-specific score. The Royal Marsden Hospital (RMH) (LDH, albumin, and number of metastatic sites) and MDACC (RMH + ECOG PS) were selected as phase I prognostic scores. Hazard ratios (HR) were calculated using the Cox proportional hazard model. The prognostic values of the IMDC, RMH, and MDACC scores were assessed using the Likelihood ratio (LR) χ2 test and the c-index.
Results
Between June 2015 and Sept 2019, 43 patients were enrolled in an early phase trial and 12 were enrolled in >1 trial leading to a total of 57 trial participations. 97% of patients had received prior platinum therapy and 60% had received a prior checkpoint inhibitor. Median overall survival (OS) and progression-free survival (PFS) were significantly shorter with increasing RMH (n=56), or MDACC scores (n=56), but not with increasing Bellmunt score (n=57). The RMH (c-index=0.658, LR χ2=11.8, p=0.008) and MDACC scores (c-index =0.66, LR χ2=12.76, p=0.01) outperformed the Bellmunt score (c-index=0.537, LR χ2=0.36, p=0.9) in predicting OS. The RMH, and MDACC scores, but not the Bellmunt score, were also predictive of PFS. The RMH (c-index=0.65, LR χ2=8.65, p=0.03) and MDACC scores (c-index =0.613, LR χ2=6.87, p=0.1) again outperformed the Bellmunt score (c-index=0.572, LR χ2=1.35, p=0.7).
Conclusions
The RMH and MDACC prognostic scores were predictive of survival in patients with mBC, and performed better than the Bellmunt score at time of enrollment on early phase clinical trials. Further prospective validation of these scores are warranted.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vivek Subbiah.
Funding
Has not received any funding.
Disclosure
P. Msaouel: Honoraria (self): Pfizer, Bristol-Myers Squibb, Mirati, Exelixis; Advisory/Consultancy: Mirati, Bristol-Myers Squibb; Research grant/Funding (institution): Mirati, Bristol-Myers Squibb, Takeda, Gateway for Cancer Research. F. Meric-Bernstam: Advisory/Consultancy: Aduro BioTech Inc., DebioPharm, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., Genentech Inc., IBM Watson, Jackson Laboratory, Kolon Life Science, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Samsung Bioepis, Seattle Genetics Inc., Tyra Bi; Advisory/Consultancy: : Immunomedics, Inflection Biosciences, Mersana Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Silverback Therapeutics, Spectrum Pharmaceuticals; Research grant/Funding (self): Aileron Therapeutics, Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Mill; Honoraria (self): Chugai Biopharmaceuticals, Mayo Clinic, Rutgers Cancer Institute of New Jersey. A. Naing: Research grant/Funding (institution): NCI; Research grant/Funding (institution): EMD Serono; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Healios Onc; Research grant/Funding (institution): Nutrition; Research grant/Funding (institution): Atterocor; Research grant/Funding (institution): Amplimmune; Research grant/Funding (institution), Tavel: ARMO BioSciences; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Karyopharm ; Research grant/Funding (institution): Incyte; Research grant/Funding (institution), Advisory board: Novartis; Research grant/Funding (institution): Regeneron; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Bristol Myers Squibb; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution), Advisory board: CytomX ; Research grant/Funding (institution): Neon ; Research grant/Funding (institution): Calithera ; Research grant/Funding (institution): TopAlliance ; Research grant/Funding (institution), Advisory board: Kymab; Research grant/Funding (institution): PsiOxus; Advisory/Consultancy: Novartis; Advisory/Consultancy: Genoma. S. Piha-Paul: Research grant/Funding (self): AbbVie, Inc.; ABM therapeutics, Inc; Acepodia, Inc; Alkermes, Inc.; Aminex Therapeutics; Amphivena Therapeutics, Inc.; BioMarin Pharmaceutical, Inc; Boehringer Ingelheim; Bristol Myers Squib; Chugai Pharmaceutical Co., Ltd; Daichi Sankyo, Inc.; Eli Lilly;. F. Janku: Research grant/Funding (institution): Novartis, Gentech, BioMed Valley Discoveries, Plexxikon, Deciphera, Piqur, Symphogen, Bayer; Advisory/Consultancy: Deciphera; Research grant/Funding (institution): FujiFilm Corporation and Upsher-Smith Laboratories; Research grant/Funding (institution): Astex, Asana, Astellas, Agios, Proximagen, Bristol-Myers Squibb ; Advisory/Consultancy: IFM Therapeutics; Advisory/Consultancy: Synlogic; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: Ideaya, PureTech Health ; Honoraria (self): Trovagene; Honoraria (self): Immunomet; Honoraria (self): Jazz Pharmaceuticals; Honoraria (self): Sotio. S. Pant: Research grant/Funding (self): Mirati Therapeutics, Inc., Eli Lilly, Red Hill Biopharma Ltd., Xencor, Five Prime Therapeutics, Novartis, Rgenix, Sanofi-Aventis, Arqule, Bristol-Myers Squibb, Onco Response, Sanofi US Services Inc., GlaxoSmith Kline; Advisory/Consultancy, Speaker Bureau/Expert testimony: Tyme, Inc., Zymeworks, Xencor and 4-D Pharma. T.A. Yap: Research grant/Funding (self): 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 Ge; Advisory/Consultancy: 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. D.S. Hong: Research grant/Funding (self): 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, Novarti; Travel/Accommodation/Expenses: Bayer,LOXO, miRNA, Genmab, AACR, ASCO, SITC; Advisory/Consultancy: 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, WebMD; Shareholder/Stockholder/Stock options: Molecular Match (Advisor), OncoResponse (Founder), Presagia Inc (Advisor). M.T. Campbell: Research grant/Funding (institution): Exelixis, Janssen, AstraZeneca, Pfizer/EMD Serono, ApricityHealth; Honoraria (institution): Exelixis, AstraZeneca, Eisai, EMD Serono, Pfizer; Travel/Accommodation/Expenses, Education Programs non-CME: Roche, Pfizer/EMD Serono. A.Y. Shah: Research grant/Funding (self): Eisai, BMS, EMD Serrono; Honoraria (self): Pfizer, Oncology Information Group. N. Tannir: Honoraria (self): Pfizer, Novartis, Bristol-Myers Squibb, Exelixis, Nektar, Eisai Medical Research, Ono, Eli Lilly, Oncorena, Ipsen, Surface Oncology, Neoleukin ; Advisory/Consultancy: Pfizer, Novartis, Bristol-Myers Squibb, Exelixis, Nektar, Eisai Medical Research, Ono, Oncorena, Ipsen, Surface Oncology, Neoleukin ; Research grant/Funding (institution): Bristol-Myers Squibb, Exelixis, Pfizer, Nektar, Calithera, Lilly, Mirati, Ar, Takeda, Epizyme, Eisai; Travel/Accommodation/Expenses: Pfizer, Novartis, Bristol-Myers Squibb, Nektar, Eisai Medical Research, Ono, Oncorena, Surface Oncology, Lilly, Ipsen, Neoleukin . A.O. Siefker-Radtke: Advisory/Consultancy: Merck, Bavarian Nordic, Seattle Genetics, Genentech, Janssen, Mirati, AstraZeneca, Nektar Therapeutics, Pfizer; Speaker Bureau/Expert testimony: Janssen. V. Subbiah: Research grant/Funding (self): Roche/ Genentech, Novartis, Bayer, GlaxoSmithKline, Nanocarrier, Vegenics, Celgene, Northwest Biotherapeutics, Berghealth, Incyte, Fujifilm, Pharmamar, D3, Pfizer, Multivir, Amgen, Abbvie, Alfa-sigma, Agensys, Boston Biomedical, Idera Pharma, Inhibrx, Exe; Travel/Accommodation/Expenses: Pharmamar, ASCO, ESMO, Helsinn, Incyte; Advisory/Consultancy: Helsinn, LOXO Oncology/ Eli Lilly, R-Pharma US, Incyte, QED pharma, Medimmune, Novartis; Travel/Accommodation/Expenses, Other Expenses: Medscape. All other authors have declared no conflicts of interest.