(335) Patient characteristics, treatment patterns, and real-world outcomes among patients in the US with human epidermal growth factor receptor 2 (HER2)-expressing solid tumors

Background: : In April 2024, trastuzumab deruxtecan (T-DXd) was granted accelerated approval in the US for patients (pts) with unresectable/metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors following disease progression after prior treatment (Tx) and with no alternative Tx options. Prior to this US approval, HER2 IHC testing was primarily performed in pts with breast and gastric tumors; thus, real-world data on the Tx patterns and outcomes of pts with other HER2 IHC 3+/2+ solid tumors are limited.

Objective: : Describe demographic and clinical characteristics, and Tx patterns and real-world response rates (rwRRs) by HER2 IHC status among pts in the US with HER2 IHC 3+/2+ solid tumors.

Methods: : This retrospective cohort study used data from the Tempus multi-modal database (a primarily US-based population combining curated sources and electronic health records). Adult (≥18 years) pts with HER2 IHC 3+ or 2+ advanced (Stage IV) solid tumors, diagnosed from Jan 2016 to Dec 2023, were selected for analysis. Pts with multiple solid tumors, breast or gastric cancer, clinical trial enrollment during the study period, or Tx with T-DXd were excluded.

Results: : Among 392 identified pts (median age 66 years [IQR 57.0–72.0]; 66.6% female; 42.5% White), tumor types included endometrial (26.5%), colorectal (25.5%), NSCLC (18.9%), and other solid tumors (29.1%, < 15 pts per tumor type). 127 and 265 pts had HER2 IHC 3+ and 2+ tumors, respectively. First-line (1L) Tx was received by 276 pts. In pts with HER2 IHC 3+ tumors, the most common Tx was immunotherapy-based regimens (32.6%; n/N=30/92) at 1L, chemotherapy or HER2-targeted therapy (28.9%; n/N=11/38) at second line (2L), and chemotherapy (36.8%; n/N=7/19) at third line (3L); rwRRs (95% CI) were 40% (30, 51), 8% (2, 22), and 21% (7, 46) with 1L, 2L, and 3L Tx, respectively. In pts with HER2 IHC 2+ tumors, the most common Tx was chemotherapy (44.6%; n/N=82/184) at 1L, chemotherapy or immunotherapy-based regimens (28.8%; n/N=23/80) at 2L, and chemotherapy or biologic ± chemotherapy (28.2%; n/N=11/39) at 3L; rwRRs (95% CI) were 39% (32, 47), 19% (11, 29), and 21% (10, 37) with 1L, 2L, and 3L Tx, respectively.

Conclusions: : These data provide valuable insights into the Tx patterns and rwRRs for pts with IHC 3+/2+ solid tumors between 2016 and 2023. The poor rwRRs shown here, particularly with 2L/3L Tx, highlight the need for effective biomarker-directed Tx options in these pts. However, results should be interpreted with caution owing to the selective pt population who underwent HER2 IHC testing when it was not routinely performed.

Sponsorship:: AstraZeneca, Daiichi Sankyo.