Multidisciplinary Strategies for Dato-DXd in Pretreated EGFR-Mutated Advanced NSCLC (Full Video)
Key Points
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Datopotamab deruxtecan (Dato-DXd) is approved for EGFR-mutated non-small cell lung cancer (NSCLC) after prior anti-EGFR therapy and platinum-based chemotherapy.
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Notable toxicities to watch for and manage with Dato-DXd include eye, lung, and oral side effects, although most patients can restart Dato-DXd once events resolve.
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To implement Dato-DXd in practice, community oncologists should form partnerships with pulmonary and ophthalmology colleagues to help monitor patients and manage toxicity.
EGFR-Mutated Metastatic NSCLC Treatment With Dato-DXd
The Oncology Brothers podcast cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Aaron Lisberg, MD, of UCLA Health; Blanca Ledezma, NP, of UCLA Health, and Sarah Sunshine, MD, of University of Maryland, to share clinical insights on Dato-DXd in EGFR-mutated NSCLC including side effects, prophylactic strategies, and multidisciplinary care.
Dato-DXd, an antibody-drug conjugate (ADC) against TROP-2, is approved for patients with EGFR-mutated locally advanced or metastatic NSCLC after prior EGFR-targeted therapy and platinum-based chemotherapy. It was granted accelerated approval based on a pooled analysis of the TROPION-Lung01 and TROPION-Lung05 trials. In the analysis, Dato-DXd had an overall response rate of 45% (95% CI, 35-54) and a median duration of response of 6.5 months (95% CI, 4.2-8.4).
Dato-DXd Side Effects and Management Strategies
Dato-DXd is associated with interstitial lung disease (ILD) pneumonitis, stomatitis and mucositis, and ocular effects like dry eyes and keratitis. Before starting Dato-DXd, oncologists need to educate patients on the potential side effects and proactive management strategies. For the oral toxicities, Dr. Lisberg assigns two mouthwashes to patients on day one, a steroidal mouthwash and a medicated oral rinse, and emphasizes the importance of good oral hygiene. ILD pneumonitis with Dato-DXd is very similar in presentation and management to immunotherapy-associated ILD, said Dr. Lisberg.
To manage ocular toxicity, patients should avoid contact lenses and use preservative-free eyedrops four times a day. Patients should also have an eye exam as early as possible when starting treatment to establish a baseline that eye changes can be tracked against, said Dr. Sunshine. Ocular toxicities are typically low-grade, but may accumulate over the course of treatment. Long-term therapy can be a balancing act of holding treatment while toxicities resolve, followed by rechallenge until toxicities again interrupt doses.
Based on the potential lung and eye toxicities, the doctors stressed the need for community oncologists implementing Dato-DXd or other ADCs to establish relationships with pulmonologists and ophthalmologists. These colleagues can help recognize when toxicities are developing, and clear patients to restart treatment when they resolve.
Typically, patients are able to restart treatment at the standard dose after toxicities resolve, but if toxicities continue to occur, a dose reduction may be warranted. Anecdotally, dose delays or reductions have not correlated to loss of tumor control in Dr. Lisberg’s practice. While the side effect management for Dato-DXd is an involved process, patients in this population have shown durable benefits and lack additional treatment options.
How Will Dato-DXd Be Sequenced in EGFR-Mutated NSCLC?
The line of therapy in which Dato-DXd is used depends on what patients received in prior lines of therapy. For patients who received osimertinib monotherapy or the MARIPOSA regimen of amivantamab plus lazertinib, they would need to go to platinum-based doublet chemotherapy with or without amivantamab before meeting the approval criteria for Dato-DXd. For patients who received the FLAURA2 regimen of osimertinib plus chemotherapy, Dato-DXd could enter as a second-line therapy.
Various active trials are also evaluating different sequences or combinations for Dato-DXd. For patients who progressed on osimertinib, the ORCHARD trial is investigating the addition of Dato-DXd while continuing osimertinib.The TROPION-Lung15 trial comparesDato-DXd, with or without continued osimertinib, toplatinum-based chemotherapy. The TROPION-Lung14 trial is examining osimertinib with or without Dato-DXd in first-line therapy.