In a poster presentation at the 2022 San Antonio Breast Cancer Symposium, Della Varghese, PharmD, PhD, and colleagues presented “A real-world evidence study of treatment patterns in patients with HER2-positive metastatic breast cancer who have received at least 2 lines of therapy,” studying second-line (2L) treatment patterns and outcomes among HER2+ metastatic breast cancer (mBC) patients in the United States.

In 2021, following the DESTINY Breast 03 trial results, fam-trastuzumab deruxtecan-nxki (T-DXd, Enhertu) was approved for the treatment of HER2+ mBC and demonstrated a significant reduction in the risk of progression compared to ado-trastuzumab emtansine (T-DM1) in 2L.

Using the Syapse Learning Health Network (LHN) database, the study authors identified 15,241 adult patients with HER2+ mBC who began 2L treatment between January 2014 to February 2021. Patient characteristics, treatment patterns (including prior metastatic treatments), time to treatment discontinuation (TTD), and reasons for 2L discontinuation were reported.

Of the 15,241 patients, 312 received at least 2L treatment; of that 312, 54% of patients initiated their 2L therapy during or after 2018. Treatment patterns that emerged consisted of most patients being White (69%) or African American (21%), with a median age of 59 years (interquartile range, 50-66; 50 for African American vs 54 for White) at the start of 2L.

Initial diagnosis was stage IV (62%); most common sites of metastasis at diagnosis were bone (52%), distant lymph node(s) (38%), liver (36%), and brain (10%).

The majority of the 312 patients (78%) had received a trastuzumab-based (T-based) regimen as first-line (1L) therapy; 37% had received two lines of therapy in the metastatic setting, 28% received three, and 35% received at least four lines.

In the 2L group, 89% of the 312 patients received a HER2-targeted treatment (monotherapy or combination); the most frequent 2L regimens included T-DM1 monotherapy (29%), trastuzumab/pertuzumab/taxane (10%), and T-DM1/trastuzumab (8%).

In the 3L group, the most frequently reported regimens were T-DM1 monotherapy (19%), T-DXd monotherapy (10%), and capecitabine/lapatinib (8%).

Approximately 88% of the 312 patients discontinued 2L therapy. Median TTD of 2L was 7.2 months (95% confidence interval [CI], 6.5-8.9); however, for a subgroup of patients who received a T-based regimen in their 2L (N = 116), median TTD was 10.6 months (95% CI, 7.4-14.0). Discontinuation due to progression/worsening of cancer was seen in 47% of patients, and 17% discontinued from intolerance/toxicity in the absence of progression.

Overall, the treatment path of patients with HER2+ mBC is variable in real-world clinical practice. About two-thirds of the 2L patients had to receive a subsequent therapy; disease progression was the most common reason for 2L treatment discontinuation, which reflects a need to improve outcomes for patients in 2L HER2+ disease.

Varghese D, Cruz G, Johanson C, et al. A real-world evidence study of treatment patterns in patients with HER2-positive metastatic breast cancer who have received at least 2 lines of therapy. Presented at: 2022 San Antonio Breast Cancer Symposium. December 6-10, 2022. Poster P1-11-19.