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Randomized Controlled Trial
. 2024 Aug 1;7(8):e2429772.
doi: 10.1001/jamanetworkopen.2024.29772.

Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial

Heikki Joensuu  1 , Judith Fraser  2 , Hans Wildiers  3 , Riikka Huovinen  4 , Päivi Auvinen  5 , Meri Utriainen  1 , Kenneth K Villman  6 , Päivi Halonen  1 , Helena Granstam-Björneklett  7 , Minna Tanner  8 , Liisa Sailas  9   10 , Taina Turpeenniemi-Hujanen  11 , Jeffrey Yachnin  12 , Teppo Huttunen  13 , Patrick Neven  3 , Peter Canney  2 , Vernon J Harvey  14 , Pirkko-Liisa Kellokumpu-Lehtinen  8 , Henrik Lindman  15
Affiliations
Randomized Controlled Trial

Long-Term Outcomes of Adjuvant Trastuzumab for 9 Weeks or 1 Year for ERBB2-Positive Breast Cancer: A Secondary Analysis of the SOLD Randomized Clinical Trial

Heikki Joensuu et al. JAMA Netw Open. .

Abstract

Importance: The standard adjuvant treatment for patients with ERRB2-positive breast cancer is chemotherapy plus 1 year of trastuzumab. Shorter durations of trastuzumab administration improve cardiac safety, but more information is needed about their effect on survival.

Objective: To compare survival outcomes after 9-week vs 1-year administration of trastuzumab with the same adjuvant chemotherapy.

Design, setting, and participants: This post hoc secondary analysis of an open-label, multicenter, noninferiority-design randomized clinical trial included women aged 18 years or older with early ERBB2-positive, axillary node-negative or axillary node-positive breast cancer who were enrolled from January 3, 2008, to December 16, 2014, at 65 centers in 7 European countries. The current exploratory analysis was conducted after achieving the maximum attainable follow-up data when the last patient enrolled had completed the last scheduled visit in December 2022.

Intervention: Chemotherapy consisted of 3 cycles of docetaxel administered at 3-week intervals followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide at 3-week intervals. Trastuzumab was administered in both groups for 9 weeks concomitantly with docetaxel. In the 9-week group, no further trastuzumab was administered after chemotherapy, whereas in the 1-year group, trastuzumab was continued after chemotherapy to complete 1 year of administration.

Main outcomes and measures: The primary objective was disease-free survival (DFS). Distant DFS and OS were secondary objectives. Survival between groups was compared using the Kaplan-Meier method and log-rank test or univariable Cox proportional hazards regression.

Results: Among the 2174 women analyzed, median age was 56 years (IQR, 48-64 years). The median follow-up time was 8.1 years (IQR, 8.0-8.9 years); 357 DFS events and 176 deaths occurred. Trastuzumab for 9 weeks was associated with shorter DFS compared with trastuzumab for 1 year (hazard ratio [HR], 1.36; 90% CI, 1.14-1.62); 10-year DFS was 80.3% in the 1-year group vs 78.6% in the 9-week group. The 5-year and 10-year OS rates were comparable between the 9-week and 1-year groups (95.0% vs 95.9% and 89.1% vs 88.2%, respectively; HR for all time points, 1.20; 90% CI, 0.94-1.54). In multivariable analyses, 9-week treatment was associated with shorter DFS compared with 1-year treatment (HR for recurrence or death, 1.36; 95% CI, 1.10-1.68; P = .005), but there was no between-group difference in OS (HR, 1.22; 95% CI, 0.90-1.64; P = .20). Only 4 patients (0.2%) died of a cardiac cause.

Conclusions and relevance: In this secondary analysis of a randomized clinical trial, 1-year vs 9-week adjuvant trastuzumab was associated with improved DFS among patients with ERRB2-positive breast cancer receiving chemotherapy, but there was no significant difference in OS between the groups.

Trial registration: ClinicalTrials.gov Identifier: NCT00593697.

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Conflict of interest statement

Conflict of Interest Disclosures: Prof Joensuu reported receiving personal fees from Orion Pharma and the Maud Kuistila Foundation, nonfinancial support from Neutron Therapeutics, and grants from Mersana Therapeutics and Defense Therapeutics outside the submitted work and having stock ownership in Orion Pharma and Sartar Therapeutics. Dr Fraser reported being supported during the conduct of the study by Sanofi-Aventis with a per-patient recruited payment to the Beatson West of Scotland Cancer Centre Trial to recompense for additional work generated by the trial. Dr Wildiers reported receiving advisory board fees from Roche to the institute during the conduct of the study and lecture fees and advisory board fees to the institute from Augustine Therapeutics, Gilead, Novartis, Immutep, Eli Lilly, AstraZeneca, Seagen, Daiichi Sankyo, and Pfizer outside the submitted work. Dr Halonen reported receiving travel grants from Bayer, MSD, and Servier outside the submitted work. Dr Tanner reported receiving consulting and lecture fees from Roche Finland and institutional support from Roche for serving as principal investigator in a trial. Mr Huttunen reported receiving personal fees from Helsinki University Hospital for statistical services during the conduct of the study. Dr Harvey reported receiving grants from Auckland Hospital during the conduct of the study. Dr Kellokumpu-Lehtinen reported serving on the data safety monitoring board for TILT Biotherapeutics outside the submitted work. Dr Lindman reported receiving personal fees for advising from AstraZeneca, Novartis, Pfizer, Amgen, and Daiichi Sankyo and for serving on speakers’ bureaus for Servier, Amgen, Celgene, AstraZeneca, and Roche outside the submitted work. No other disclosures were reported.

Figures

Figure.
Figure.. Survival Outcomes After the Date of Randomization
Hash marks indicate patients without an event. HR indicates hazard ratio.
See this image and copyright information in PMC

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