Tucatinib therapy combined with trastuzumab and capecitabine was shown to be well-tolerated in the HER2CLIMB clinical trial of patients with HER2-positive breast cancer, according to adverse event (AE) data presented at the virtual 2020 ASCO Annual Meeting.

Using the randomized HER2CLIMB trial data, which compared the use of tucatinib plus trastuzumab and capecitabine with placebo, Alicia Frances Clare Okines, MBBCh, The Royal Marsden NHS Foundation Trust, London, United Kingdom, and co-investigators explored the management of AEs in this setting.

Because recipients of tucatinib had longer durations of toxicity than those given placebo, time-at-risk exposure-adjusted incidence rates of diarrhea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and palmar-plantar erythrodysesthesia syndrome (PPE) were calculated as the number of patients with an event divided by the total exposure time-at-risk of an initial occurrence of the event.

Ms Okines et al conducted time-to-event analyses for diarrhea, PPE, and AST/ALT/bilirubin (collectively).

The majority of diarrhea and elevated AST/ALT/bilirubin cases in the tucatinib and control arms were grade 1/2 and manageable with dose modifications or (in some cases) antidiarrheals.

The median time to onset of diarrhea was shorter with tucatinib than in the control arm, and the median time to first onset of AST/ALT/bilirubin and PPE were cycles 1 and 2.

In the tucatinib arm, 49.7% of cycles with reports of diarrhea used antidiarrheals compared with 39.8% of cycles in the control arm; the median duration of antidiarrheal use was 3 days per cycle in each arm.

Per protocol, prophylactic antidiarrheals were not compulsory.

When adjusted for exposure, the difference in grade ≥3 AEs between treatment arms was similar for diarrhea and PPE, but the difference was reduced for AST and ALT.

“Tucatinib with trastuzumab and capecitabine was well-tolerated,” Ms Okines and colleagues concluded.

“Elevated liver enzymes were higher on the tucatinib arm, but were transient and reversible,” they added, noting that tucatinib therapy discontinuation because of AEs was rare.—Hina M. Porcelli

Okines AFC, Paplomata E, Wahl TA, et al. Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB). Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 1043.