163O - Patient-reported outcomes (PROs) from DESTINY-Breast03, a randomized phase 3 study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC)

Background

In DESTINY-Breast03 (NCT03529110), T-DXd showed superior progression-free survival by BICR vs T-DM1 (HR, 0.28 [95% CI, 0.22-0.37]; P < 0.001) and manageable safety in pts with HER2+ MBC. PRO measures incorporate pts’ perspective in clinical trials to assess effect of treatment on health-related quality of life (QoL). Here, PROs and hospitalization rate for T-DXd vs T-DM1 (May 21, 2021, data cutoff) are reported.

Methods

Pts with HER2+ (IHC 3+ or IHC 2+/ISH+) MBC whose disease progressed on or after trastuzumab and a taxane were assigned 1:1 to T-DXd or T-DM1. PRO endpoints were assessed before infusion on day 1 of the first 3 21-day cycles, then every 2 cycles, at end of treatment, at 40-days’ follow-up, then every 3 months until end of follow-up; endpoints included European Organization for Research and Treatment of Cancer QoL questionnaires (EORTC QLQ-C30; primary variable: global health status [GHS]/QoL scale score) and the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analog scale (VAS). Analyses included change from baseline (CFB) and time to definitive deterioration (TDD). Hospitalization-related endpoints were also measured.

Results

Compliance for questionnaires was >97% at baseline and >80% for cycles 3-29. QLQ-C30 baseline GHS scores recorded for T-DXd (n = 253) and T-DM1 (n = 260) were similar. At end of treatment, mean CFB was not meaningfully different vs baseline (<10-point CFB) in both arms. Median TDD of QLQ-C30 GHS was 9.7 mo for T-DXd vs 8.3 mo for T-DM1 (HR, 0.88 [95% CI, 0.70-1.11]), and all prespecified QLQ-C30 subscales presented longer TDD with T-DXd, including emotional functioning (HR, 0.69 [95% CI, 0.53-0.89]) and pain (HR, 0.75 [95% CI, 0.59-0.95]). Median TDD of EQ-5D-5L VAS was 13.2 mo for T-DXd vs 8.5 mo for T-DM1 (HR, 0.77 [95% CI, 0.61-0.98]). With T-DXd vs T-DM1, 18 pts (6.9%) vs 19 pts (7.2%) were hospitalized; median time to first hospitalization was 219.5 vs 60.0 days, respectively.

Conclusions

The improved efficacy and manageable toxicity reported previously for T-DXd, together with this evidence of maintained or improved QoL supports the overall benefit of T-DXd for pts with HER2+ MBC.

Clinical trial identification

NCT03529110.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Marianna B. Johnson, PhD, and Eileen McIver, PhD, of ApotheCom, and was funded by Daiichi Sankyo, Inc.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

Daiichi Sankyo, Inc., AstraZeneca.

Disclosure

G. Curigliano: Financial Interests, Personal, Other, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Advisory Board, Honoraria: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer, Roche; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Novartis, Lilly, Roche, AstraZeneca, Daiichi Sankyo, Exact Sciences, Seagen, Gilead, Celcuity; Financial Interests, Personal, Officer: ESMO, LILT, EUSOMA; Financial Interests, Personal, Other: National Health Council. K. Dunton: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Rosenlund: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Janek: Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. J. Cathcart: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Liu: Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc.; Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. P.A. Fasching: Financial Interests, Personal, Other, Honoraria: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Personal, Advisory Board: Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck Sharp & Dohme, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia, Sanofi Aventis, Gilead; Financial Interests, Institutional, Research Grant: Cepheid, BioNTech; Financial Interests, Personal, Officer: TRIO. H. Iwata: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, Chugai, AstraZeneca, Sanofi, Lilly, MSD, Pfizer; Financial Interests, Personal, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer; Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Chugai, AstraZeneca, Lilly, MSD, Pfizer.