Global trends in the distribution of cancer types among patients in oncology phase I trials, 1991–2015
- 41 Downloads
Background Systematic analyses regarding cancer types of patients enrolled in oncology phase I trials are scarce. The global distribution, time-dependent change, and regional differences were evaluated. Methods A systematic search of the PubMed database, in which all single-agent phase I trials permitting the enrollment of all-comer patients with any type of solid tumor published between January 1991 and December 2015 were specified, was performed. Trials expected to enroll specific patient populations were excluded according to predefined criteria. Results Eight hundred and sixty-six eligible trials, which had enrolled 29,112 advanced solid tumor patients, were identified. Colorectal (n = 7510; 25.8%) and lung cancer (n = 3212; 11.0%) were the most prevalent solid tumors, followed by sarcoma (n = 1756; 6.0%), breast cancer (n = 1623; 5.6%), and renal cancer (n = 1589; 5.5%). The proportion of patients with either colorectal or lung cancer tended to decrease over time. The proportion of trials, in which patients with either of these two cancers accounted for ≥50.0% of the total number of patients in each trial, also decreased: 33 of 67 trials (31/67) (46.3%) in 1991–1995, 58/142 (40.8%) in 1996–2000, 59/223 (26.5%) in 2001–2005, 38/189 (20.1%) in 2006–2010, and 41/245 (16.7%) in 2011–2015. Instead, the proportion of patients with various types of cancer increased, leading to diversification of enrolled patients. Conclusions The distribution of cancer types among patients in phase I trials has changed. The comprehensive review of the distribution of solid tumor types could contribute to flexible trial designs and optimal patient recruitment.
KeywordsPhase I trial Cancer Cancer type Global trend
Itahashi and Yamamoto had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Itahashi, Yamamoto.
Acquisition, analysis, or interpretation of data: all authors.
Drafting of the manuscript: Itahashi, Shimizu, Yamamoto.
Critical revision of the manuscript for important intellectual content: all authors.
Statistical analysis: Itahashi.
Administrative, technical, or material support: Koyama, Yamamoto.
Study Supervision: Yamamoto.
Compliance with ethical standards
Conflict of interest disclosures
Kota Itahashi has no conflicts of interest.
Toshio Shimizu has provided consulting for Takeda Oncology; received honoraria from Ono Pharmaceutical, ONO Pharma Taiwan CO., LTD., Boehringer Ingelheim, Taiho Pharmaceutical and Chugai Pharmaceutical; and received research funding from Takeda Oncology, PharmaMar, Bristol-Myers Squibb Japan, Daiichi Sankyo, SymBio Pharmaceuticals, Five Prime Therapeutics, and 3D Medicine.
Takafumi Koyama has no conflicts of interest.
Shunsuke Kondo has received research funding from Astrazeneca, Eli Lilly, and Pfizer.
Yutaka Fujiwara has provided consulting for Ono Pharmaceutical and Bristol-Myers Squibb Japan; participated in speakers’ bureau for Ono Pharmaceutical, Bristol-Myers Squibb Japan, MSD, and Taiho Pharmaceutical; and received research funding from AstraZeneca, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Lilly Japan, Novartis, Bristol-Myers Squibb Japan, MSD, Merck Serono, Abbvie, and Incyte.
Noboru Yamamoto has provided consulting for Eisai, Takeda, Otsuka Pharmaceutical, and OncoTherapy Science; participated in speakers’ bureau for Bristol-Myers Squibb Japan, Pfizer, AstraZeneca, Lilly Japan, Ono Pharmaceutical, and Chugai Pharmaceutical; and received research funding from Chugai Pharmaceutical, Taiho Pharmaceutical, Eisai, Quintiles, Astellas Pharma, Novartis, Daiichi Sankyo, Boehringer Ingelheim, Takeda, Kyowa Hakko Kirin, Bayer, Pfizer, Bristol-Myers Squibb Japan, Ono Pharmaceutical, and Bayer.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
For this type of study formal consent is not required.
We presented this work at the Annual Meeting of the American Society of Clinical Oncology; June 2–6, 2017; Chicago, Illinois.
All opinions expressed by the authors in this paper are solely the author’s opinions and do not reflect the opinions of the journal.
- 5.Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (London, England) 387(10027):1540–1550. https://doi.org/10.1016/s0140-6736(15)01281-7 CrossRefGoogle Scholar
- 6.Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin CC, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M, Bang YJ (2016) Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 17(6):717–726. https://doi.org/10.1016/s1470-2045(16)00175-3 CrossRefPubMedGoogle Scholar
- 7.Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520. https://doi.org/10.1056/NEJMoa1500596 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Tsimberidou AM, Iskander NG, Hong DS, Wheler JJ, Falchook GS, Fu S, Piha-Paul S, Naing A, Janku F, Luthra R, Ye Y, Wen S, Berry D, Kurzrock R (2012) Personalized medicine in a phase I clinical trials program: the MD Anderson Cancer Center initiative. Clin Cancer Res 18(22):6373–6383. https://doi.org/10.1158/1078-0432.CCR-12-1627 CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Schwaederle M, Zhao M, Lee JJ, Lazar V, Leyland-Jones B, Schilsky RL, Mendelsohn J, Kurzrock R (2016) Association of Biomarker-Based Treatment Strategies with Response Rates and Progression-Free Survival in refractory malignant neoplasms: a meta-analysis. JAMA Oncology 2(11):1452–1459. https://doi.org/10.1001/jamaoncol.2016.2129 CrossRefPubMedGoogle Scholar
- 14.Italiano A, Massard C, Bahleda R, Vataire AL, Deutsch E, Magne N, Pignon JP, Vassal G, Armand JP, Soria JC (2008) Treatment outcome and survival in participants of phase I oncology trials carried out from 2003 to 2006 at Institut Gustave Roussy. Ann Oncol 19(4):787–792. https://doi.org/10.1093/annonc/mdm548 CrossRefPubMedGoogle Scholar
- 15.Karavasilis V, Digue L, Arkenau T, Eaton D, Stapleton S, de Bono J, Judson I, Kaye S (2008) Identification of factors limiting patient recruitment into phase I trials: a study from the Royal Marsden Hospital. Eur J Cancer 44(7):978–982. https://doi.org/10.1016/j.ejca.2008.02.040 CrossRefPubMedGoogle Scholar
- 16.Roberts TG Jr, Goulart BH, Squitieri L, Stallings SC, Halpern EF, Chabner BA, Gazelle GS, Finkelstein SN, Clark JW (2004) Trends in the risks and benefits to patients with cancer participating in phase 1 clinical trials. Jama 292(17):2130–2140. https://doi.org/10.1001/jama.292.17.2130 CrossRefPubMedGoogle Scholar
- 20.Weber JS, Levit LA, Adamson PC, Bruinooge S, Burris HA, Carducci MA, Dicker AP, Gonen M, Keefe SM, Postow MA, Thompson MA, Waterhouse DM, Weiner SL, Schuchter LM (2015) American Society of Clinical Oncology policy statement update: the critical role of phase I trials in cancer research and treatment. J Clin Oncol Off J Am Soc Clin Oncol 33(3):278–284. https://doi.org/10.1200/jco.2014.58.2635 CrossRefGoogle Scholar
- 22.Von Hoff DD, Stephenson JJ Jr, Rosen P, Loesch DM, Borad MJ, Anthony S, Jameson G, Brown S, Cantafio N, Richards DA, Fitch TR, Wasserman E, Fernandez C, Green S, Sutherland W, Bittner M, Alarcon A, Mallery D, Penny R (2010) Pilot study using molecular profiling of patients' tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol Off J Am Soc Clin Oncol 28(33):4877–4883. https://doi.org/10.1200/JCO.2009.26.5983 CrossRefGoogle Scholar