Oncologists’ perspectives on individualizing dose selection for patients with metastatic cancer.
Authors: Jimenez Rachel , Schenkel Caroline , Levit Laura , Hu Bonnie , Harvey R. Donald , Morrison Vicki A. , Pollastro Teri , Waterhouse David Michael , Weekes Colin D. , Williams Grant Richard , Bruinooge Suanna Steeby , Garrett-Mayer Elizabeth , Peppercorn Jeffrey M. 
Published: June 2022

1531

Background: The goal of treatment for patients with metastatic cancer (MC) is to prolong and maintain quality of life. Patients and oncologists have questioned the current paradigm of initial dose selection for systemic therapy and want additional information about the potential trade-offs between efficacy and toxicity. However, empirical data on oncologists’ dose selection strategies and beliefs is lacking. Methods: ASCO conducted an international survey of medical oncologists who treat patients with metastatic breast or gastrointestinal cancers. Survey questions addressed experience with and attitudes towards reducing the standard dose of the first cycle of systemic therapy to minimize potential toxicity. The survey was open November 14 to December 13, 2021. Results: Among 3,099 eligible ASCO members, 367 completed the survey (response rate 12%), including 117 general oncologists (GO), 142 breast specialists (BRS), and 108 GI specialists (GIS). 77% of respondents practice in the US, 94% had experience leading a clinical trial, and 50% had been caregivers or patients themselves. Most respondents (52%) reported reducing the first dose of systemic agents at least 10% of the time in patients with MC to minimize toxicities. GIS were more likely to report reducing the first dose at least 10% of the time (72% vs. 50% of GO and 51% of BRS, p <.005). Of those who dose reduce, 89% reported discussing potential tradeoffs between efficacy and toxicity with patients. Among 10 common breast cancer drugs, capecitabine (76%) was the most likely to be dose reduced at initiation while tamoxifen (4%) was the least likely. Among 10 common GI cancer drugs, regorafenib (78%), capecitabine (71%) and sorafenib (66%) were most commonly dose reduced at initiation, while bevacizumab (7%) and panitumumab (8%) were the least likely. Overall, 65% of respondents agreed it is acceptable to lower starting doses to reduce side effects even at the potential expense of efficacy, with younger clinicians more likely to agree vs. older clinicians (72% age < 50 vs. 55% age > 50, p <.005). While the majority (53%) believe that oncologists should start with the recommended dose and lower it in response to side effects, GIS were more likely to disagree with this approach compared to BRS or GO (57% vs. 37% and 36% respectively, p <.005). In contrast, 45% of respondents believe that oncologists should start at a lower dose and consider increasing the dose for future cycles if the drug is well tolerated. There was strong support (89%) for future trials that seek to determine the minimal effective dose as opposed to the maximum tolerated dose. Conclusions: Oncologists frequently dose reduce to avoid toxicity in patients with MC but practices and attitudes regarding dose reduction vary considerably. Further research is needed to establish optimal dosing during drug development and to support oncologists and patients in selecting the starting dose in clinical practice.