The optimal duration for ADC maintenance therapy is a major unanswered question, with current trials using fixed timeframes like 12 or 24 months. Experts suggest that future practice may rely on biomarkers like ctDNA to personalize treatment duration, stopping therapy when molecular remission is achieved to minimize toxicity and tailor care.
Despite next-generation sequencing (NGS) identifying ERBB2 amplification, clinicians still order immunohistochemistry (IHC) tests. The IHC score (e.g., 3+) provides a quantitative measure of protein expression, which can offer greater confidence in the efficacy of HER2-targeted therapies and help decide between treatment options.
For GYN cancer patients with HER2 1+ expression who are ineligible for trials and have exhausted standard options, clinicians may consider off-label TDXD. Experts acknowledge some activity exists in this 'HER2-low' population but caution that efficacy is lower than in HER2 3+ cases and urge thoughtful consideration as new ADCs with different targets emerge.
Clinicians are not concerned about using the antibody-drug conjugate (ADC) TDXD in patients who have already progressed on the monoclonal antibody trastuzumab. Drawing from extensive breast cancer data, TDXD remains a highly effective option in this post-trastuzumab setting, demonstrating that prior exposure to the antibody alone does not confer resistance to the ADC.
For first-line HER2+ advanced endometrial cancer, a key debate is whether to use a chemo-immunotherapy regimen or a chemo-trastuzumab regimen. The former preserves future clinical trial eligibility, which often requires prior IO, while the latter saves a powerful IO combination for a later line of therapy.
When sequencing antibody-drug conjugates (ADCs), the critical factor for efficacy may not be switching the antibody target, but rather switching the cytotoxic payload. For example, using an ADC with a different payload (like tizotumab vedotin’s MMAE) after one with a topoisomerase inhibitor (like TDXD) could overcome resistance, shifting the paradigm from 'ADC after ADC' to 'payload after payload'.