More detrimental effects on health-related quality of life were reported, and lasted for at least 12 months, with the combination of trastuzumab plus chemotherapy compared with trastuzumab alone in older patients with HER2-positive breast cancer, according to an analysis of the phase 3 RESPECT trial.
More detrimental effects on health-related quality of life (HRQoL) were reported, and lasted for at least 12 months, with the combination of trastuzumab (Herceptin) plus chemotherapy compared with trastuzumab alone in older patients with HER2-positive breast cancer, according to an analysis of the phase 3 RESPECT trial (NCT01104935) that was published in the Journal of Clinical Oncology.1
Results from the analysis showed that among patients aged 70 to 80 years older who were randomized to either trastuzumab alone or plus chemotherapy, the QoL deterioration at 2 months and 12 months after treatment was significantly lower for those receiving the monotherapy (31% and 19%, respectively) vs those receiving the combination (48% and 38%; P = .016 and P = .009, respectively). At 3 years posttreatment, there were no significant differences in HRQoL between the 2 arms.
“The negative impacts of adding adjuvant chemotherapy to trastuzumab on global QoL, physical wellbeing and functional wellbeing [FWB], morale, and activity capacity were not transient but lasted for at least 12 months,” lead study author Naruto Taira, MD, PhD, of the Department of Breast and Endocrine Surgery, Okayama University Hospital, in Okayama, Japan, and coinvestigators wrote in the publication. “During the treatment period, the [chemotherapy-induced peripheral neuropathy] frequency was high. After 36 months, there were no detrimental effects of chemotherapy for any QoL items.”
The addition of trastuzumab to chemotherapy for patients with HER2-postive breast cancer has significantly improved outcomes, and the regimen has become standard of care in the adjuvant setting. However, due to lack of data, a conclusion on the benefits of adjuvant chemotherapy in patients 70 years old and older has never been reached by the Early Breast Cancer Trialists’ Collaborative Group. As such, these older patients have been treated based on the same criteria as younger patients, despite the know higher risk for severe chemotherapy-related toxicity in this group.
Because of this, investigators sought to examine whether 1 year of trastuzumab monotherapy was noninferior to the combination in terms of disease-free survival on the RESPECT trial. The primary end point of that trial was not met; however, given the known adverse events of chemotherapy, investigators examined the benefits of trastuzumab monotherapy based on patient-reported outcomes and QoL data. Additionally, investigators sought to examine the duration of chemotherapy-associated toxicities in this patient population, as data are limited.
The randomized, controlled, open-label, multicenter phase 3 RESPECT study that enrolled patients between 70 and 80 years old with confirmed stage I to stage IIIA breast cancer, who had undergone curative surgery, and had an ECOG performance status of 0 or 1.
Patients were randomized 1:1 to receive either trastuzumab alone or with chemotherapy. In both study arms, patients received trastuzumab for 1 year, and those in the combination arm received chemotherapy selected from prescribed regimens at their physicians’ discretion.
The chemotherapy regimens included weekly paclitaxel for 12 cycles; docetaxel every 3 weeks for 4 cycles; docetaxel plus cyclophosphamide every 3 weeks for 4 cycles; doxorubicin (or epirubicin) plus cyclophosphamide every 3 weeks for 4 cycles; fluorouracil, epirubicin, and cyclophosphamide every 3 weeks for 6 cycles, or 4 to 6 cycles; cyclophosphamide, methotrexate, and fluorouracil every 4 weeks for 6 cycles; docetaxel, carboplatin, and trastuzumab every 3 weeks for 6 cycles.
Stratification factors included age (70 to 75 years vs 76 to 80 years), ECOG performance status (0 vs 1), hormone receptor status, pathologic nodal status, and participating institution.
Patient QoL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G) scale, which evaluates 27 items associated with cancer care QoL, including: 7 items for physical wellbeing, 7 items for social and family wellbeing, 6 items for emotional wellbeing, and 7 items for functional wellbeing.
Questions on the FACT-G sheet include response choices that range from 0 to 4, for a total score of up to 108 points, and higher scores are associated with better QoL. Additionally, physical wellbeing, QoL, and anxiety and depression were assessed using both the Philadelphia Geriatric Center Morale Scale (PGCMS), in which scores range from 0 to 17, and the Hospital Anxiety and Depression Scale (HADS), in which scores range from 0 to 21. On the PGCMS, higher scores are associated with higher morale, and on the HADS, higher scores are correlative with higher anxiety and depression.
Moreover, chemotherapy-induced peripheral neuropathy [CIPN] and activity capacity were assessed using the Patient Neurotoxicity Questionnaire (PNQ) and Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), respectively.
All assessments were completed by patients at trial registration, as well as at 2 months, 12 months, and 36 months after the start of treatment, except for the PGCMS and TMIG-IC, which were omitted after 2 months.
Overall, 275 patients were enrolled on the RESPECT study, and 231 (84%) participated in the QoL assessment (116 on trastuzumab monotherapy and 115 on the combination).
Among those in the QoL substudy analysis, the mean age was 73.8 years old, and the majority (92.5%) had an ECOG performance status of 0. Additionally, most patients (77%) were negative for lymph node metastases, and stage I disease was the most prevalent histology (46%). In terms of breast cancer surgery, most patients (70%) had undergone mastectomy.
In the monotherapy arm, 45% of patients were estrogen receptor (ER)–positive or progesterone receptor (PR)–positive and 55% were negative. In the combination arm, ER positivity and PR positivity was evenly split among patients (50% in both).
Response rates for the QoL assessments at 2 months, 12 months, and 36 months were 90%, 79%, and 89%, respectively, in the trastuzumab monotherapy cohort; in the combination cohort, these rates were 82%, 79%, and 84%, respectively.
Additional data showed that QoL improvement at 2 months was superior in the monotherapy arm at 38% vs 15% with the combination (P <.001); this was similar at 12 months, at 43% vs 25%, respectively (P = .021).
Moreover, scores from the FACT-G scale were significantly better in the monotherapy group at 2 months, at 81.0 vs 73.9 with the combination; at 12 months, these scores were 83.0 and 77.9, respectively. There were no significant differences in QoL seen between the study arms at 36 months (79.8 vs 77.2, respectively).
“These findings may provide relief for patients seeking standard treatment with a combination of chemotherapy and trastuzumab,” study authors concluded. “Care and social support for at least 1 year are required for older patients with breast cancer who receive adjuvant chemotherapy in addition to anti-HER2 therapy.”