Dealing with lung toxicity
“We are getting new drugs to improve the treatment of cancer, but they always come with a price in terms of toxicity,” observed David Cameron, MD, professor of medical oncology at Edinburgh University in Scotland. Dr. Cameron chaired the session.
“Several measures were taken to identify and mitigate ILD,” across all the T-DXd studies, Dr. Powell explained. As well as the independent adjudication committee, available guidelines were followed and updated on how to diagnose and treat drug-induced lung injuries, and a “safe use” campaign was run in 2019.
Many patients in the early MBC studies were recruited before these measures were in place, such as the use of systemic steroids to manage low-grade events.
The bottom line, however, is that if a patient develops ILD then treatment should be stopped, Dr. Powell said. “Patients with grade 1 events may restart once the ILD has resolved, but those with grade 2 to 4 events must discontinue treatment.”
Dr. Powell concluded: “The overall clinical data support the positive risk-benefit profile of T-DXd. Phase 3 randomized controlled trials in breast cancer are ongoing.”
ILD also seen in monarchE trial with abemaciclib
Data on ILD events seen in the phase 3 monarchE trial were also reported separately at the ESMO Breast Cancer virtual meeting. The analysis population included 2,971 patients who had been treated with the CDK 4/6 inhibitor abemaciclib (Verzenio) together with endocrine therapy and 2,800 who had received endocrine therapy alone in the early-stage, adjuvant advanced breast cancer setting.
Most ILD (97%) events that occurred were single occurrences, with any grade of ILD occurring in a higher percentage of patients treated with abemaciclib with endocrine therapy than endocrine therapy alone (2.9% vs. 1.2%). Grade 3 events occurred in a respective 0.4% and 0.0% of patients.
So who’s at risk?
The risk factors for ILD and pneumonitis are not well characterized with either of the two drugs discussed, Dr. Burstein observed.
“In the abemaciclib experience, it looked like obesity might be a predisposing factor, with trastuzumab deruxtecan, it looked like patients of Asian ancestry were greater risk, but we need more data to really understand who’s at jeopardy.”
Dr. Burstein observed: “This is something patients need to be aware of as they’re contemplating this treatment.”
While data to prove the benefit of the drug need to mature, Dr. Burstein “would likely discontinue therapy” if a patient were to develop ILD or pneumonitis and treat accordingly.
As for T-DXd, he said: “It’s important that patients know that lung disease is a potentially severe side effect of treatment and that any respiratory symptoms need to be jumped on quickly.”
While prospective studies are now needed, and the phase 3 data should help to better understand the risk of ILD with T-DXd, Dr. Burstein believes it will be important to develop algorithms to ensure the safe administration of the drug.
These algorithms should include “appropriate surveillance and monitoring, especially as we think about trying to move this drug forward into the early stage setting where we’re using it in women who have favorable prognosis, and potentially curative situations for breast cancer.”
The trastuzumab deruxtecan trials were cosponsored by Daiichi Sankyo and AstraZeneca. The monarchE trial was supported by Eli Lilly.
Dr. Powell acknowledged receiving personal fees for acting as an advisory or consultant to both companies as well as to Voluntis. Dr. Burstein had nothing to disclose, and Dr. Cameron had no relevant financial interests in the data being presented.