Real-world data comparison of time to next treatment for patients with HER2 low metastatic treated with either chemotherapy or fam-trastuzumab deruxtecan-nxki following chemotherapy in the metastatic setting.
Authors: Gorantla Vikram C. , Rui Anna , Rosenfeld Stephan B. , Kudrik Fred J. , Vasudevan Anupama , Sura Teena , Gart Mike , Kanovsky Doug , Brenneman Dawn , Varughese Prateesh , Scott Jeffrey A. , Choksi Rushir J. , Geller Robert B. , Blanc Simon 
Published: June 2024

e13169

Background: In the Destiny-04 trial, pts who received TDxd following chemo in the metastatic setting experienced 10.1 months of progression-free survival compared to 5.4 months for pts who received chemo. We sought to evaluate the TTNT, a surrogate for progression-free survival, and OS using real-world data to assess whether such pts see similar benefits beyond the clinical trial setting. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify 252 breast cancer pts for the analysis. Pts were identified as HER2 low (IHC of 1+ or an IHC of 2+ with an ISH/FISH negative result) at the time of treatment initiation following the chemo in the metastatic setting, and each started treatment on or after June 1, 2022, through December 31, 2023. The first treatment following chemo in the metastatic setting was used for comparison. TTNT was measured from the treatment start to either the initiation of a subsequent line of therapy or death. Descriptive analyses were used, proportions were compared using a chi-squared test, and TTNT and OS were analyzed using a Kaplan-Meier analysis. Results: Median (IQR) age was 56 (47.5, 66). 100% of the pts were female; 108 (42.9%) received TDxd with a median (IQR) age of 65.5 at treatment start, and 144 (57.1%) received chemo (most commonly paclitaxel, capecitabine, carboplatin, gemcitabine) with a median (IQR) age of 64 (54, 74) at treatment. TDxd pts had higher ECOG scores (p<0.05) and higher rates of lung (p<0.05) and bone (p<0.05) metastases. Median TTNT was 9.0 months (95% confidence interval [CI], 7.9 to 11.1) for pts who received TDxd compared to 5.4 months (95% CI, 4.6 to 6.0) for pts who received chemo ( p<0.01). Median OS was not reached (NR) in TDxd pts (95% CI, 13.0 to NR) whereas it was 13.1 months (95% CI, 10.8 to NR) in the pts treated with chemo ( p<0.01). The percent of TDxd pts who were deceased was 22.2% compared to 34.7% for chemo treated pts. The probability of pts on therapy after 6 months was 72.8% (95% CI, 62.3% to 80.8%) for those who received TDxd compared to 38.0% (95% CI, 28.9% to 17.1%) for those who received chemo ( p<0.01). The probability of pts on therapy after 12 months was 31.4% (95% CI, 19.7% to 43.8%) for those who received TDxd compared to 17.1% (95% CI, 9.7% to 26.3%) for those who received chemo ( p<0.05). Conclusions: The real-world comparison of TDxd to chemo in the metastatic setting for pts with HER2low breast cancer demonstrated a statistically significant difference in both OS and TTNT, reaffirming the results of the Destiny-04 trial. However, 57% of pts were found to not have received TDxd, suggestingan opportunity to improve outcomes in HER2low breast cancer pts.