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Sarah Badaoui, Andrew Rowland, Michael J. Sorich, Ashley M. Hopkins, Regarding the Article by Rugo et al., The Oncologist, Volume 26, Issue 7, July 2021, Page e1285, https://doi.org/10.1002/onco.13781
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We read with great interest Rugo et al. [1], whose study evaluated the association between early adverse events (AEs) and progression-free survival (PFS) in patients with hormone receptor–positive, human epidermal growth receptor 2–negative advanced breast cancer treated with abemaciclib. However, we highlight two additional analyses that would significantly enhance the completeness of the results reported: (a) impact of dose omissions/interruptions and (b) prognostic association of early AEs by grade of severity.
It is comforting to both patients and clinicians that an abemaciclib dose reduction from 150 mg to 50–100 mg resulted in no difference in PFS [1], highlighted by 16% and 12% of abemaciclib-treated patients enrolled across MONARCH 2 and MONARCH 3 requiring a dose reduction due to diarrhea or neutropenia, respectively. Importantly, study reports highlight that investigators also managed AEs through dose omissions/interruptions, which occurred in 17% and 17% of patients due to diarrhea and neutropenia, respectively [1]. Information regarding the association between dose omissions/interruptions and PFS would be warranted to provide a comprehensive analysis of the management of AEs with abemaciclib.
Although we appreciate that the main focus of analyses was the treatment effect difference (abemaciclib arms compared with placebo) by early AE subgroups, we believe that reporting the prognostic impact of diarrhea and neutropenia for individuals treated with abemaciclib would provide important complementary information—particularly if analyzed by toxicity grade (severity). McAndrew et al. [2] have recently reported a significantly prolonged PFS for patients who experienced low-grade neutropenia within the first 56 days of palbociclib monotherapy (hazard ratio, 0.29; 95% confidence interval: 0.11–0.74; p = .01). To complement this future area of research, information on the association between abemaciclib-induced diarrhea/neutropenia by grade of severity and PFS would be required.
The information from both analyses would provide insight regarding whether low-grade early AEs may have value as a dose titration marker to improve dose optimization. Several studies have successfully investigated dose escalation to low-grade AEs as a mechanism to increase efficacy of other targeted therapeutics [3, 4].
In summary, the results reported by Rugo et al. are generally reassuring to patients initiating abemaciclib, but information regarding the impact of abemaciclib dose omissions/interruptions on PFS and the association between early AEs by grade and PFS would provide further valuable insights.
Acknowledgments
Cancer Council South Australia; National Breast Cancer Foundation, PF-17-007.
Disclosures
Andrew Rowland: Pfizer Worldwide Research and Development (RF); Michael J. Sorich: Pfizer (RF). The other authors indicated no financial relationships.
(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board
References
Author notes
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