Management of adverse events in patients with HER2+ metastatic breast cancer treated with tucatinib, trastuzumab, and capecitabine (HER2CLIMB)


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Session type:

Alicia Okines1, Elisavet Paplomata2, Tanya Wahl2, Gail Wright2, Stephanie Sutherland3, Erik Jakobsen2, Frances Valdes-Albini2, Arlene Chan2, Amy Clark4, Alison Conlin2, Maryam Lustberg2, Jennifer Specht2, Timothy Pluard2, Xiaofu Zhu2, Ian Krop5, Karen Gelmon6, Dennis Slamon2, Jorge Ramos2, Wentao Feng2, Erika Hamilton2
1Royal Marsden NHS Foundation Trust, 2Other, 3Mount Vernon Cancer Centre, 4University of Pennsylvania, 5Dana-Farber Cancer Institute, 6BC Cancer Agency

Abstract

Background

Tucatinib (TUC), approved in multiple regions for HER2+ metastatic breast cancer (MBC), is a highly selective HER2-directed tyrosine kinase inhibitor with minimal EGFR inhibition. HER2CLIMB is a randomized trial of TUC vs placebo (Pbo) in combination with trastuzumab and capecitabine in patients (pts) with HER2+ MBC. The most common G ≥3 adverse events (AEs) with higher incidence on TUC (diarrhea, palmar-plantar erythrodysesthesia syndrome [PPE], and elevated liver enzymes) are described herein.

Method

AEs were classified by MedDRA Version 22.0 or higher and severities were classified using Version 4.03 of the CTCAE criteria. Safety data were reviewed annually by an Independent Data Monitoring Committee. AEs were treatment-emergent, and recorded after the first dose through 30 days after the last dose. Time-to-event analyses were conducted for AST/ALT/bilirubin (in aggregate), diarrhea, and PPE.

Results

Diarrhea and elevated AST/ALT/bilirubin on both TUC and Pbo were primarily G1/2 and manageable with dose modifications, and in some cases of diarrhea, with antidiarrheal treatment. Median time to diarrhea onset was shorter on TUC than control. For AST/ALT/bilirubin and PPE, median time to first onset was Cycles 1 and 2.

 

 

Diarrhea

Elevated

AST/ALT/bilirubin

PPE

TUC

Pbo

TUC

Pbo

TUC

Pbo

Pts with any event, %

80.9

53.3

21.3/20/18.6

11.2/6.6/10.2

63.4

52.8

G ≥3 events

12.9

8.6

4.5/5.4/0.7

0.5/0.5/2.5

13.1

9.1

Median days to onset

12

22

36

32

33

34.5

Events resolved, %

79.6

84.1

83.7

68.8

54.2

58.3

Median days to resolution

8

6

22

26.5

62.5

51

Dose holds, %

13.9

8.6

5.4/6.4/8.2

1.0/0.5/7.1

6.4

2

Dose reductions, %

5.7

4.6

4.2/4.7/2.2

1.0/0.5/1.0

1.2

0.5

Dose discontinuations, %

1.0

0.5

0.7/1.0/0.7

0.5/0.5/0.5

0

0

TUC=tucatinib arm; Pbo=placebo arm

 

On TUC, antidiarrheals were used in 49.7% of cycles in which diarrhea was reported (39.8% on Pbo); when used, the median duration of use on each arm was 3 days/cycle. Prophylactic antidiarrheals were not required per protocol.

Conclusion

TUC with trastuzumab and capecitabine was well-tolerated. Rates of G ≥3 diarrhea and PPE were similar between treatments. Elevated liver enzymes were higher on TUC, but were transient and reversible. Discontinuation of TUC due to AEs was rare.

Impact statement