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Patient-Reported Outcomes of Trastuzumab Deruxtecan Therapy vs Treatment of Physician's Choice in Patients With HER2+ MBC
TAKE-HOME MESSAGE
- This study was a patient-reported outcome analysis of the DESTINY-Breast02 trial, which evaluated patients with advanced HER2-positive breast cancer after progression on trastuzumab emtansine in the advanced setting and randomized them to receive trastuzumab deruxtecan (T-DXd) or treatment of physician's choice (TPC), which included capecitabine with either trastuzumab or lapatinib. T-DXd delayed the median time to deterioration in quality of life compared with TPC (14.1 months vs 5.9 months). The median time to hospitalization was longer with T-DXd than with TPC (133 days vs 83 days).
- Despite the fact that patients received T-DXd longer than they received TPC, there was a longer time to deterioration with T-DXd, suggesting that deterioration was occurring as a result of disease progression and not adverse events. These data support the use of T-DXd in the treatment of advanced HER2-positive breast cancer that had progressed on trastuzumab emtansine.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
In DESTINY-Breast02, patients with HER2-positive unresectable or metastatic breast cancer who received trastuzumab deruxtecan demonstrated superior progression-free and overall survival compared with those receiving treatment of physician's choice. We present the patient-reported outcomes (PROs) and hospitalisation data.
METHODS
In this randomised, open-label, phase 3 trial conducted at 227 clinical sites globally, enrolled patients had to be aged 18 years or older with HER2-positive unresectable or metastatic breast cancer that had progressed on trastuzumab emtansine and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (2:1) using block randomisation (block size of 3) to receive trastuzumab deruxtecan (5·4 mg/kg intravenously once every 21 days) or treatment of physician's choice by an independent biostatistician using an interactive web-based system. Patients and investigators remained unmasked to treatment. Treatment of physician's choice was either capecitabine (1250 mg/m2 orally twice per day on days 1-14) plus trastuzumab (8 mg/kg intravenously on day 1 then 6 mg/kg once per day) or capecitabine (1000 mg/m2) plus lapatinib (1250 mg orally once per day on days 1-21), with a 21-day schedule. The primary endpoint, which was progression-free survival based on blinded independent central review, has previously been reported. PROs were assessed in the full analysis set (all patients randomly assigned to the study) using the oncology-specific European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), breast cancer-specific EORTC Quality of Life Questionnaire Breast 45 (QLQ-BR45), and the generic HRQoL EQ-5D-5L questionnaire. Analyses included change from baseline and time to definitive deterioration for PRO variables of interest and hospitalisation-related endpoints. This study is registered with ClinicalTrials.gov, NCT03523585, and is closed to recruitment.
FINDINGS
Between Sept 6, 2018, and Dec 31, 2020, 608 patients were randomly assigned to receive either trastuzumab deruxtecan (n=406; two did not receive treatment) or treatment of physician's choice (n=202; seven did not receive treatment). Overall, 603 patients (99%) were female and five (<1%) were male. The median follow-up was 21·5 months (IQR 15·2-28·4) in the trastuzumab deruxtecan group and 18·6 months (IQR 8·8-26·0) in the treatment of physician's choice group. Median treatment duration was 11·3 months (IQR 6·2-20·5) in the trastuzumab deruxtecan group and approximately 4·5 months in the treatment of physician's choice group (4·4 months [IQR 2·5-8·7] with trastuzumab; 4·6 months [2·1-8·9] with capecitabine; and 4·5 months [2·1-10·6] with lapatinib). Baseline EORTC QLQ-C30 global health status (GHS) scores were similar with trastuzumab deruxtecan (n=393) and treatment of physician's choice (n=187), and remained stable with no clinically meaningful change (defined as ≥10-point change from baseline) over time. Median time to definitive deterioration was delayed with trastuzumab deruxtecan compared with treatment of physician's choice for the primary PRO variable EORTC QLQ-C30 GHS (14·1 months [95% CI 10·4-18·7] vs 5·9 months [4·3-7·9]; HR 0·5573 [0·4376-0·7099], p<0·0001) and all other prespecified PROs (EORTC QLQ-C30 subscales, EORTC QLQ-BR45 arm and breast symptoms, and EQ-5D-5L visual analogue scale). Patient hospitalisation rates were similar in the trastuzumab deruxtecan (92 [23%] of 406) and treatment of physician's choice (41 [20%] of 202) groups; however, median time to hospitalisation was 133 days (IQR 56-237) with trastuzumab deruxtecan versus 83 days (30-152) with treatment of physician's choice.
INTERPRETATION
Overall, GHS and quality of life were maintained for both treatment groups, with prespecified PRO variables favouring trastuzumab deruxtecan over treatment of physician's choice, suggesting that despite a longer treatment duration, there was no detrimental impact on patient health-related quality of life with trastuzumab deruxtecan. When considered with efficacy and safety data from DESTINY-Breast02, these results support the overall benefit of trastuzumab deruxtecan for patients with HER2-positive unresectable or metastatic breast cancer previously treated with trastuzumab emtansine.
FUNDING
Daiichi Sankyo and AstraZeneca.
Additional Info
Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial
Lancet Oncol 2024 May 01;25(5)614-625, T Fehm, F Cottone, K Dunton, F André, I Krop, YH Park, M De Laurentiis, Y Miyoshi, A Armstrong, MR Borrego, R Yerushalmi, FP Duhoux, T Takano, W Lu, A Egorov, SB KimFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Studies evaluating patient-reported outcomes (PROs) provide important data for assessing the value of anti-cancer treatments in maintaining patients’ quality of life (QOL). Treatment of metastatic breast cancer aims to not only maximize efficacy but also to preserve QOL. While our pivotal trials generate efficacy and toxicity data as a basis for FDA approval, only PRO analyses directly address the QOL patients can expect on the treatment under investigation. In this era of shared decision–making, PRO analyses provide additional data that patients can readily understand and use to help make decisions regarding potential treatment options.
When trastuzumab deruxtecan (T-DXd) was first FDA-approved for HER2-positive metastatic breast cancer, there was great enthusiasm about efficacy but also significant concerns surrounding interstitial lung disease (ILD). Two patients in DESTINY-Breast02 suffered from fatal ILD related to T-DXd, and 10% developed any grade ILD compared with <1% any grade ILD with treatment of physician’s choice (TPC). The improvement in median time to hospitalization with T-DXd over TPC (133 days vs 83 days) with a similar overall hospitalization rate between arms suggests that these patients are at greater risk of hospitalization related to symptoms of cancer progression than from ILD. These data, in combination with truly impressive efficacy data, help clinicians feel comfortable with the therapeutic index of T-DXd.
Patients considering treatment with T-DXd are often more concerned about common cancer symptoms like pain and side effects like fatigue and nausea. The current analysis showed that median time to definitive deterioration was significantly longer with T-DXd compared with TPC across prespecified variables including physical functioning, emotional functioning, and pain. These data can provide reassurance to patients considering T-DXd who prioritize QOL in making treatment decisions.
Studies evaluating patient-reported outcomes (PROs) provide important data for assessing the value of anti-cancer treatments in maintaining patients’ quality of life (QOL). Treatment of metastatic breast cancer aims to not only maximize efficacy but also to preserve QOL. While our pivotal trials generate efficacy and toxicity data as a basis for FDA approval, only PRO analyses directly address the QOL patients can expect on the treatment under investigation. In this era of shared decision–making, PRO analyses provide additional data that patients can readily understand and use to help make decisions regarding potential treatment options.
When trastuzumab deruxtecan (T-DXd) was first FDA-approved for HER2-positive metastatic breast cancer, there was great enthusiasm about efficacy but also significant concerns surrounding interstitial lung disease (ILD). Two patients in DESTINY-Breast02 suffered from fatal ILD related to T-DXd, and 10% developed any grade ILD compared with <1% any grade ILD with treatment of physician’s choice (TPC). The improvement in median time to hospitalization with T-DXd over TPC (133 days vs 83 days) with a similar overall hospitalization rate between arms suggests that these patients are at greater risk of hospitalization related to symptoms of cancer progression than from ILD. These data, in combination with truly impressive efficacy data, help clinicians feel comfortable with the therapeutic index of T-DXd.
Patients considering treatment with T-DXd are often more concerned about common cancer symptoms like pain and side effects like fatigue and nausea. The current analysis showed that median time to definitive deterioration was significantly longer with T-DXd compared with TPC across prespecified variables including physical functioning, emotional functioning, and pain. These data can provide reassurance to patients considering T-DXd who prioritize QOL in making treatment decisions.