Early detection key in management of lung disease linked to trastuzumab deruxtecan
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Lung disease that patients with cancer experience from the antibody-drug conjugate fam-trastuzumab deruxtecan-nxki can be treated effectively if detected early and managed promptly, according to study results published in ESMO Open.
Background and methods
“The accumulating experience with antibody-drug conjugate treatment for advanced cancers suggest these agents are effective and that adverse events, such as drug-induced interstitial lung disease, are common,” Charles A. Powell, MD, MBA, Janice and Coleman Rabin professor of medicine and chief of pulmonary critical care and sleep medicine at Icahn School of Medicine at Mount Sinai, told Healio. “Fam-trastuzumab deruxtecan-nxki [Enhertu; AstraZeneca, Daiichi Sankyo] is approved for treatment of patients with advanced HER2-positive breast cancer, advanced HER2-mutant non-small cell lung cancer and HER2-positive gastric carcinoma.”
During early phase clinical trials of trastuzumab deruxtecan, researchers identified fatal cases of interstitial lung disease (ILD), an adverse event of special interest, Powell added.
“In response, the sponsors established an adjudication process that was led by me,” he continued. “The adjudication committee is comprised of international experts in pulmonary, radiology and oncology who independently review all suspected cases of ILD and reach consensus on the incidence of ILD and whether it is attributable to a study drug. While there are similarities to the ILD events associated with other cancer drugs, such as immune checkpoint inhibitors, it was apparent that there are differences that are important to communicate to physicians and patients in the cancer community.”
For this reason, Powell and colleagues sought to assess cases of ILD/pneumonitis among 1,150 patients (median age, 60 years) included in four phase 1 and five phase 2 studies and treated with at least one 5.4 mg/kg dose of trastuzumab deruxtecan for breast cancer (44.3%), gastric cancer (25.6%), lung cancer (17.7%), colorectal cancer (9.3%) and other cancer types (3%).
Patients received a median four lines of prior therapy. Median treatment duration was 5.8 months.
Key findings
Results showed an overall incidence of adjudicated treatment-associated ILD/pneumonitis of 15.4%. Twenty-five patients (2.2%) experienced a grade 5 event, and 137 (77.4%) had a grade 1 or grade 2 event. Most (87%) experienced their first event within 1 year.
In addition, the adjudication committee found onset of ILD/pneumonitis earlier than investigators identified for 53.2% of events, for a median difference in onset date of 43 days.
Moreover, researchers identified several baseline factors potentially associated with an increased risk for adjudicated treatment-associated ILD/pneumonitis, including age younger than 65 years, study enrollment in Japan, trastuzumab deruxtecan dosed higher than 6.4 mg/kg, oxygen saturation less than 95%, moderate/severe renal impairment, presence of lung comorbidities and time since initial diagnosis longer than 4 years.
Implications
“ILD is a known risk factor for several cancer therapies, including trastuzumab deruxtecan, which can be severe, life-threatening and fatal,” Powell said.
“These study results suggest that close monitoring and proactive management may reduce the risk for ILD, and patient awareness and ongoing education can aid in early detection,” Powell continued. “Important next steps are to conduct studies to better understand risk factors for ILD onset and for ILD severity, as well as to develop approaches to enhance monitoring and education to increase early identification and management of ILD.”
References:
- Powell CA, et al. ESMO Open. 2022;doi:10.1016/j.esmoop.2022.100554.
- Prompt recognition and treatment found effective for lung disease in patients who received new drug for advanced cancer (press release). Available at: www.mountsinai.org/about/newsroom/2022/prompt-recognition-and-treatment-found-effective-for-lung-disease-in-patients-who-received-new-drug-for-advanced-cancer. Published Aug. 11, 2022. Accessed Sept. 27, 2022.
For more information:
Charles A. Powell, MD, MBA, can be reached at charles.powell@mssm.edu.
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