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Call to Action: TROP2 ADCs in Lung Cancer
Call to Action: Misperceptions on TROP2-Targeted Antibody–Drug Conjugates in Lung Cancer

Released: February 24, 2023

Expiration: February 23, 2024

Stephen V. Liu
Stephen V. Liu, MD
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Key Takeaways
  • A survey of oncology healthcare professionals revealed key misperceptions around TROP2-targeted antibody–drug conjugates for the treatment of patients with lung cancer, including a need for clarity on mechanism of action and how to identify patient candidates.
  • To learn more about the evolving role of TROP2-targeted antibody–drug conjugates in the management of NSCLC, please visit the CCO website often as this educational program unfolds.

Antibody–drug conjugates (ADCs) targeting the transmembrane protein TROP2 are an emerging treatment option for patients with advanced non-small-cell lung cancer (NSCLC). In this commentary, Stephen Liu, MD, discusses findings from a recent survey conducted to assess awareness of key issues related to this promising treatment paradigm in lung cancer care among a global audience of oncology healthcare professionals.

Key Finding 1: Understanding the Mechanism of TROP2-Targeted ADCs
Survey results suggest that healthcare professionals caring for patients with lung cancer need more information on how these agents work, including key factors contributing to their efficacy (ie, antibody specificity, cleavable drug linker, specific payload, and drug-to-antibody ratio) and the multiple mechanisms by which they exert an antitumor effect (ie, direct cytotoxicity, bystander effect, and elicitation of an immune response). Furthermore, there appears to be uncertainty around the nature of TROP2 as a therapeutic target and how TROP2-targeted ADCs can be beneficial for patients with lung cancer. Of note, TROP2 is expressed across lung cancer subtypes, with expression observed in both nonsquamous and squamous NSCLC.

Key Finding 2: Identifying Candidates for TROP2-Targeted ADCs
Only 1 in 3 survey respondents were aware that TROP2 testing by immunohistochemistry is NOT currently required for patients to be considered candidates for treatment with a TROP2-targeted ADC on a clinical trial. Although this story is still being written, early data have shown that these agents are effective independent of TROP2 expression, suggesting that TROP2 likely will not be a useful biomarker of response to these agents. However, we still hope to find some way to enrich patients who will derive benefit from being treated with a TROP2-targeted ADC.

Key Finding 3: Efficacy of TROP2-Targeted ADCs in NSCLC
Approximately one half of the survey respondents incorrectly thought that the demonstrated antitumor response rate of TROP2-targeted ADC therapy is as high as the rate for traditional targeted agents (eg, tyrosine kinase inhibitors) used in the treatment of advanced NSCLC with actionable driver mutations (ie, overall response rates ≥50%). In reality, overall response rates observed with these agents so far have been in the range of 15% to 30% in patients with heavily pretreated disease. We may see increased efficacy as we move these drugs into earlier stages of the disease course. That said, I want to remind all of the readers that development of these drugs is in early stages, and we are still figuring out how to best use them.

Want to Learn More?
To learn more about the evolving role of TROP2-targeted ADCs in the management of NSCLC, please visit the CCO website often as this educational program unfolds. Upcoming activities will include a CME-certified text module and downloadable slideset capturing a panel discussion among 5 lung cancer experts led by Dr Liu, which will provide additional expert insights on the above topics and more; a series of expert-authored commentaries; and a guided infographic focused on management of adverse events associated with these agents.

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