Volkmar Müller, MD, PhD: Moving on to the new drugs, there are fantastic and exciting developments we can discuss. One aspect we can discuss are new studies and combined therapies, tucatinib. There are several ongoing studies. Dr Criscitiello can you comment on that?

Carmen Criscitiello, MD, PhD: Yes, there are…several ongoing trials with combinations of tucatinib and trastuzumab deruxtecan. One is the HER2CLIMB-02 trial, which is a phase 3 study in which patients with metastatic HER2 [human epidermal growth factor receptor 2]–positive breast cancer, who have had prior treatment with taxane and trastuzumab [INAUDIBLE], are randomized to receive either T-DM1 [trastuzumab emtansine] plus placebo or T-DM1 [trastuzumab emtansine] in combination with tucatinib. In this study, baseline brain MRI is required, and patients with stable, progressing, or untreated brain metastases may be eligible. The primary end point of the study is progression-free survival. Overall survival and objective response rate are key secondary end points of the study.

Another ongoing trial is HER2CLIMB-04, which looks at a combination of tucatinib and trastuzumab deruxtecan. This is a single-arm, open-label, phase 2 trial that evaluates the efficacy and safety of those combinations with HER2+ metastatic breast cancer with at least 2 prior anti-HER2 regimens in the metastatic setting. There’s a similar study, the DESTINY-Breast07 trial, which is a phase 1b/2 trial with multiple arms; 1 of those arms is assessing the safety of tucatinib plus trastuzumab deruxtecan. In the HER2CLIMB-04 trial, patients with the brain metastases, including the active brain metastases, may be included. The primary end point is confirmed objective response rate when looking at their assessment. The secondary end points are progression-free survival, duration of response, disease control rate, overall survival, and safety.

Volkmar Müller, MD, PhD: You mentioned brain metastases, which is an important point. The longer we have survival, there’s an increasing rate of brain metastases. For the HER2CLIMB trial, nearly 50% of the patients had brain metastases. You mentioned that patients with active brain metastases are eligible. In your clinical practice, do you differentiate between patients with active and progressing brain metastases and stable brain metastases? Does that have any implications for treatment in your clinical practice?

Carmen Criscitiello, MD, PhD: These situations are clinically diverse. Stable brain metastases are those previously treated with no evidence of progression. Active progressing brain metastases are those previously treated with progression of existing, new, or untreated lesions at baseline. Stable brain metastases are not a problem because they don’t affect the choice of treatment. Whereas progressing brain metastases in patients who have already received radiation therapy, cannot undergo further radiation therapy. Here, it’s 3 years.

Volkmar Müller, MD, PhD: That’s the most clinical implicant aspect. We need special trials. In the context of trastuzumab deruxtecan there are some ongoing trials.

Transcript edited for clarity.