1459P Albumin as a simple criterion to reduce early mortality (EM) in gastric cancer (GC) trials
M. Ozguroglu1, K. Shitara2, K-W. Lee3, C.S. Fuchs4, H.C. Chung5, M. Di Bartolomeo6, J. Chao7, Z.A. Wainberg8, C. Caglevic9, I. Kudaba10, E. Van Custem11, M. Garrido12, J. Lee13, J. Ma14, Z.A. Cao14, S. Shah14, C-S. Shih14, P. Bhagia14, L. Wyrwicz15, J. Tabernero16
1Medical Oncology, Istanbul University- Cerrahpas¸a, Cerrahpas¸a School of Medicine, Istanbul, Turkey;2Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan;3Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;4Internal Medicine, Yale Cancer Center, Smilow Cancer Hospital, New Haven, CT, USA;5Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea;6Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;7Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA;8Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA, USA;9Medical Oncology, Cancer Research Department Fundación Arturo Lopez Perez, Santiago, Chile;10Medical Oncology, Latvian Oncology Center Rakus Gailezers, Riga, Latvia;11Oncology, University Hospitals Gasthuisberg and KU Leuven, Leuven, Belgium;12Hemato-Oncology, Ponti
fica Universidad Catόlica de Chile, Santiago, Chile;13Internal Medicine, Samsung Medical Center, Seoul, Re-public of Korea; 14Medical Oncology, Merck & Co., Inc., Kenilworth, NJ, USA; 15Oncology and Radiotherapy, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland;16Medical Oncology, Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Barcelona, Spain
Background:Some clinical trials in advanced/metastatic GC have observed that>20% of patients succumb to their disease within 3 months of enrollment. It is likely that these patients were poor performing at the time of enrollment and their inclusion is not suitable for the assessment of the efficacy of experimental therapies. This issue can be addressed by improving trial eligibility criteria.
Methods:Data from KEYNOTE-061 (NCT02370498) were analyzed retrospectively to identify general baseline factors for predicting EM using>70 baseline measurements (eg, demographic and clinical variables, lifestyle factors, tumor-related measure-ments, lab tests, and other study-specific measurements). An exclusion criterion for patients at risk for EM was then proposed based on the identified baseline factor. KEYNOTE-062 (NCT02494583), an independent study of 740 patients, was used to validate the proposed exclusion criterion for EM. Both steps were done without knowledge of the study treatment. The impact of the proposed criterion on treatment was further evaluated after unblinding in both studies.
Results:Using data from KEYNOTE-061, albumin level was the top-ranked baseline factor correlating to EM. An exclusion criterion of albumin3 g/dL was proposed, which identified 9% of the trial population. The EM rate was 53% in patients with albumin3 g/dL versus 20% in all patients regardless of albumin level (2.65 times enrichment). When applied to KEYNOTE-062, the same albumin criterion identified 8% of the trial population and the EM rate was 2.1 times enriched over that in all patients regardless of albumin level. After unblinding to study treatment and use of the proposed criterion, subsequent analysis showed improvement of pembrolizumab over the comparator in both trials.
Conclusions:Our exploratory analysis identified blood albumin level as an important measurement correlated to EM in GC studies. Exclusion of patients with albumin3 g/dL may reduce EM in clinical trials to enable a more appropriate assessment of clinical efficacy. This exploratory analysis suggests that the potential prognostic role(s) of serum albumin in select indications warrants further examination in immuno-oncology therapies in the clinical setting.
Clinical trial identification: KEYNOTE-061, NCT02370498; KEYNOTE-062, NCT02494583.
Editorial acknowledgement:Medical writing and/or editorial assistance provided by Holly C. Cappelli, PhD, CMPP, and Dana Francis, PhD, of the ApotheCom pem-brolizumab team (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp. Legal entity responsible for the study:Merck Sharp & Dohme Corp.
Funding:Merck Sharp & Dohme Corp.
Disclosure:M. Ozguroglu: Honoraria (self): Janssen, Astellas, Novartis; Honoraria (institution): JANSSEN; Advisory/Consultancy: MSD, SANOFI; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: BMS, AstraZeneca. K. Shitara: Honoraria (self): Novartis, AbbVie, and Yakult; Advisory/Consultancy: Astellas, Lilly, Bristol-Myers Squibb, Takeda, Pfizer, Ono, MSD, Taiho, Novartis, AbbVie, and GlaxoSmithKline; Research grant/Funding (institution): Astellas, Lilly, Ono, Sumoitomo Dainippon, Daiichi Sankyo, Taiho, Chugai, MSD, and Medi Science. K-W. Lee: Honoraria (self): Bristol-Myers Squibb, Eli Lilly, and Genexine; Research grant/Funding (self): Ono Pharmaceutical, Merck Sharp & Dohme Corp., AstraZeneca/MedImmune, Merck KGaA, Pfizer, MacroGenics, Green Cross Corporation, Five Prime Therapeutics, Pharmacyclics, LSK BioPharma, ALX Oncology, Zymeworks, BeiGene, Genexine, Daiichi Sankyo, and Taiho Ph. C.S. Fuchs: Leadership role: CytomX Therapeutics, Evolveimmune Therapeutics; Shareholder/Stockholder/Stock options: CytomX and Entrinsic Health exercised stock options; Advisory/Consultancy: Agios, Bain Capital, CytomX, Daiichi Sankyo, Eli Lilly, Entrinsic Health, Genetech, Merck, Taiho, Unum. H.C. Chung: Honoraria (self): Merck-Serono, Lilly, Foundation Medicine; Advisory/Consultancy: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, Beigene, Amgen, Zymework; Research grant/Funding (self): Lilly, GSK, MSD, Merck-Serono, BMS/Ono, Taiho, Amgen, Beigene. M. Di Bartolomeo: Honoraria (self): Lilly spa; Servier; Advisory/Consultancy: Taiho, Celltrion, MSD, Lilly, Quintiles, BMS, Merck-Serono, Gloria, Beigene, Amgen, Zymework; Research grant/Funding (institution): Lilly, GSK, MSD, Merck-Serono, BMS/Ono, Taiho, Amgen, Beigene. J. Chao: Advisory/Consultancy: Amgen, Macro-genics, Ono Pharmaceuticals, Foundation Medicine; Speaker Bureau/Expert testimony: Merck; Travel/Accommodation/Expenses: Amgen, Foundation Medicine, Macrogenics; Research grant/ Funding (self): Merck, Brooklyn Immunotherapeutics. Z.A. Wainberg: Advisory/Consultancy: Merck,
Ibsen, Lilly, Five prime, QED, Molecular Templates, Daiichi, Astra Zeneca; Travel/Accommodation/ Expenses: Lilly, Merck, Novartis, Daiichi. C. Caglevic: Honoraria (self): Andes Biotechnologies; Advi-sory/Consultancy: BMS, MSD, Roche, Boehrnger Ingelheim; Speaker Bureau/Expert testimony: MSD, BMS, Lilly, Roche; Research grant/Funding (self): MSD, Medivation, AstraZeneca, Roche, Astellas Pharma, BMS; Travel/Accommodation/Expenses: BMS, Roche, MSD. E. Van Custem: Advisory/Con-sultancy: Array, Astrazeneca, Bayer, Biocartis, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre-Fabre, Roche, Servier, Sirtex, Taiho; Research grant/Funding (institution): Bayer, Boehringer Ingelheim, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier paid to the institution. M. Garrido: Honoraria (self): BMS, MSD, Novartis, Roche, Pfizer, Bayer; Advisory/Consultancy: MSD, Bayer; Speaker Bureau/ Expert testimony: MSD, BMS; Travel/Accommodation/Expenses: BMS, Novartis. J. Lee: Advisory/ Consultancy: Oncologie, Seattle Genetics; Research grant/Funding (self): Astra Zeneca, Merck Sharp and Dohme, Eli Lilly and Company. J. Ma, Z.A. Cao, C-S. Shih, P. Bhagia: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Shareholder/ Stockholder/Stock options: Merck & Co., Inc., Kenilworth, NJ, USA. S. Shah: Full/Part-time employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. J. Tabernero: Advisory/Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partn. All other authors have declared no conflicts of interest.
https://doi.org/10.1016/j.annonc.2020.08.1965
1460P Impact of sites of metastatic dissemination on survival in advanced gastroesophageal adenocarcinoma
X. Wang1, O. Espin-Garcia2, C. Suzuki1, Y. Bach1, D. Jiang1, L.X. Ma1, M.J. Allen1, M.X. Honório3, E. Chen1, G. Darling4, J.C-W. Yeung4, R. Wong5, P. Veit-Haibach6, K. Sangeetha7, R.W-J. Jang8, E. Elimova1
1Medical Oncology, UHN - Princess Margaret Cancer Centre, Toronto, ON, Canada; 2Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada; 3Medical Oncology, UHN - Princess Margaret Cancer Centre, Toronto, ON, Canada;4Surgical Oncology, UHN - Princess Margaret Cancer Centre, Toronto, ON, Canada;5Radiation Oncology, UHN - Princess Margaret Cancer Centre, Toronto, ON, Canada;6Diagnostic Radiology, UHN - Princess Margaret Cancer Centre, Toronto, ON, Canada;7Pathology, UHN - Princess Margaret Cancer Centre, Toronto, ON, Canada;8Medical Oncology, Princess Margaret Cancer Center, Toronto, ON, Canada
Background:Metastatic gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with an overall poor prognosis. The impact of sites of metastatic dissemina-tion on survival is not well characterized. This study aimed to evaluate whether certain sites of metastatic disease impacts survival.
Methods:A retrospective analysis of 375 patients with metastatic GEA treated at the Princess Margaret Cancer Centre from 2006 to 2016 was performed. Sites of metastasis were determined by baseline computed tomography of chest, abdomen, and pelvis, and additional investigations as clinically indicated. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association between patient characteristics, including sites of metastases, and OS.
Results:Patients were primarily male (67%), non-Asian (85%), with Eastern Cooper-ative Oncology Group Performance Status (ECOG PS) 0e1 (81%). Median follow-up duration was 47.8 months. Median OS in this cohort was 11.8 months (95% CI: 10.2-12.9 months). Patients with lymph node only disease, compared to those with other sites of metastases, had the longest median OS (20.4 months) and PFS (11.4 months). Sites of metastases associated with decreased OS were metastases to the lung with a median OS of 9.6 months, and metastases to the bone, with a median OS of only 8.1 months. On multivariate analysis adjusting for relevant clinical factors including age, sex, and ECOG PS, the presence of lung or bone metastases were independently associated with shorter OS, with hazard ratios of 1.67 (95% CI: 1.23-2.26; p< 0.001) for presence of lung metastases and 1.84 (95% CI: 1.31-2.59; p< 0.001) for presence of bone metastases. Other sites of metastases including liver, peritoneal, adrenal, and ovarian were not associated with decreased OS. Majority of patients (68%) were treated with palliative intent platinum-based chemotherapy.
Conclusions:Patients with metastatic GEA have a poor prognosis. The presence of lung or bone metastases are independent risk factors for decreased survival. Prog-nostic models incorporating sites of metastasis should be considered in the clinical evaluation of metastatic GEA.
Legal entity responsible for the study:The authors. Funding:Has not received any funding.
Disclosure:E. Elimova: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
https://doi.org/10.1016/j.annonc.2020.08.1966
