Imaging-guided chemotherapy omission shows QoL benefits in breast cancer
medwireNews: An 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) response-adapted treatment strategy could lead to improved quality of life (QoL) for some patients with HER2-positive, early-stage breast cancer, study findings indicate.
In the phase 2 PHERGain trial, participants with stage I–IIIA, invasive, operable disease (≥1.5 cm tumor size) from 45 European hospitals were randomly assigned to join one of two treatment groups between 2017 and 2019.
Group A (n=71) received trastuzumab 600 mg plus pertuzumab at a loading dose of 840 mg, followed by 420 mg maintenance doses and chemotherapy (docetaxel 75 mg/m2, carboplatin AUC 6 mg/mL per minute) every 3 weeks for six cycles, irrespective of 18F-FDG-PET results.
Group B (18F-FDG-PET-guided group; n=285) received 2 weeks of treatment with trastuzumab and pertuzumab plus either letrozole 2.5 mg/day if postmenopausal or tamoxifen 20 mg/day if premenopausal.
After two cycles, 81% of group B participants had an 18F-FDG-PET response, defined as a reduction in the maximum standardized uptake value of at least 40% from baseline in all target lesions, with no metabolic progression of non-target lesions, and continued treatment for six further cycles. The remaining 19% were switched to six cycles of trastuzumab and pertuzumab plus chemotherapy.
All participants then underwent surgery between 2 and 6 weeks after the last dose of study treatment. After surgery, 37.9% of the group B responders had a pathologic complete response (pCR) in the breast and axilla (ypT0/is ypN0).
Writing in The Lancet Oncology, Javier Cortés (International Breast Cancer Center, Barcelona, Spain) and co-investigators say that this response rate was significantly higher than the 20.0% observed in the NeoSphere trial, which evaluated neoadjuvant HER2 blockade with trastuzumab and pertuzumab.
The pCR rate among non-responders in group B was 25.9%, while the overall pCR rates were 57.7% in group A and 35.4% in group B.
Grade 3 or 4 adverse events (AEs) were reported in 59% of 68 patients in group A versus 12% of 283 patients in group B, with serious AEs occurring in 29% and 5%, respectively.
The researchers also measured health-related (HR)QoL using the EORTC QLQ-C30 and QLQ-BR23 questionnaires. They found that 65.0% of participants in group A experienced a deterioration (≥10%) in global health status during treatment, compared with 35.5% of those in group B and 30.2% of group B responders.
“By using an 18F-FDG-PET-based, pathological response-adapted strategy in our study, up to a third of patients did not receive chemotherapy for HER2-positive, early-stage breast cancer at any time [including the adjuvant setting],” Cortés et al remark.
They add: “As expected, this de-escalation approach omitting chemotherapy was clearly associated with a more favourable toxicity profile and substantial improvement in HRQOL, representing a main goal for patients treated with curative intent.”
However, the investigators stress that “is crucial to confirm, through analysis of the planned second coprimary endpoint of 3-year invasive disease-free survival, as well as other longer-term outcome results, whether patients who avoid chemotherapy according to our 18F-FDG-PET- based, pathological response-adapted strategy have a similar prognosis to patients receiving chemotherapy with HER2 blockade.”
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