Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT)

Abstract

In the ATEMPT trial, adjuvant trastuzumab emtansine (T-DM1) compared to paclitaxel plus trastuzumab (TH) for stage I HER2-positive breast cancer improved patient-reported outcomes (PROs), while maintaining excellent disease outcomes. We report treatment discontinuation and use multivariable models to compare, patient-reported toxicity and quality-of-life (QOL) by age (≤50, >50) and treatment arm at 18 months post-enrollment among 366 eligible participants randomized in a 3:1 ratio to T-DM1 or TH. T-DM1 discontinuation was higher among women >50 vs. ≤50 (23% vs. 9%, p = 0.003, Fisher’s Exact test) with 4%, 8%, and 17% of older patients discontinuing treatment by 3, 6, and 9 months, respectively. Superior QOL with T-DM1 vs. TH was observed among women ≤50 with estimated mean difference of 6.48 (95% confidence interval (CI) 0.51–12.46) and driven by better social/family well-being and breast cancer-specific sub-scores. Among women >50, T-DM1 was associated with superior physical well-being and less activity impairment, with no differences in global QOL. Older women had decreased neuropathy with T-DM1 vs. TH. De-escalated treatment regimens for HER2 positive breast cancer may have age-varying impact on treatment tolerance, toxicities and subsequent QOL, which should be considered when selecting therapy options.Clinical Trial Registration: ClinicalTrials.gov, NCT01853748

Health-related quality of life in Her2-positive early breast cancer woman using trastuzumab: A systematic review and meta-analysis

“…The majority of the studies (Au et al, 2013;Syrios et al, 2018;Trinca et al, 2019;Conte et al, 2020;Bines et al, 2021) made use of the EORTC-QLQ-C30 questionnaire to estimate the HRQoL of women suffering from Her2-positive breast cancer, with three (Syrios et al, 2018;Conte et al, 2020;Bines et al, 2021) of these studies also making use of EORTC-QLQ-BR23. Other types of questionnaires identified were FACT-G (Sawaki et al, 2020(Sawaki et al, , 2022Taira et al, 2021), FACT-B (Sella et al, 2022), and EQ-5D-3L (Earl et al, 2020). Most of the instruments of the studies included was self-administered with the completion rate ranged from 50% to 97% (Table 1).…”

“…Eighty-one articles were eliminated according to stricter application of the inclusion criteria, leaving ten studies for our present analysis, with four of these studies being eligible for metaanalysis (Au et al, 2013;Syrios et al, 2018;Trinca et al, 2019;Conte et al, 2020). Six articles were excluded from quantitative meta-analysis due to lack of detailed data for allowing metaanalysis (Earl et al, 2020;Sawaki et al, 2020Sawaki et al, , 2022Sella et al, 2022) or comparing trastuzumab in both arms (Bines et al, 2021;Taira et al, 2021). The details of the selection process are described in Figure 1.…”

“…The included studies consisted of seven RCTs (Au et al, 2013;Conte et al, 2020;Earl et al, 2020;Sawaki et al, 2020;Bines et al, 2021;Taira et al, 2021;Sella et al, 2022) and three observational studies of cross-sectional design (Syrios et al, 2018;Trinca et al, 2019;Sawaki et al, 2022). Two studies (Trinca et al, 2019;Conte et al, 2020) involved the comparison of a group receiving trastuzumab treatment with a group receiving chemotherapy.…”

“…Three studies (Sawaki et al, 2020(Sawaki et al, , 2022Taira et al, 2021) investigated the use of trastuzumab monotherapy compared to a combination of trastuzumab and chemotherapy in the treatment of elderly breast cancer patients. Two studies (Conte et al, 2020;Sella et al, 2022) compared trastuzumab regimens with trastuzumab emtansine (T-DM1) was utilized in a study. In addition, one study (Earl et al, 2020) presented a comparison of the HRQoL profile after 6 months of trastuzumab with the HRQoL profile after 12 months of trastuzumab and a study (Bines et al, 2021) evaluated the addition of pertuzumab in trastuzumab in HER-2 positive early breast cancer.…”

“…The HRQoL of early breast cancer patients filled the questionnaire at 0, 3, 6, 9, 12, 18, and 24 months of followup (Earl et al, 2020). Patients in a study (Bines et al, 2021) completed a questionnaire on weeks 10, 13, 25, and at the end of HER2-targeteted therapy (12 months) while another study on weeks 18 (Sella et al, 2022). Finally, an HRQoL profile was made of patients receiving treatment during the observational studies (Syrios et al, 2018;Trinca et al, 2019).…”