medwireNews: The final analysis of the CALOR trial confirms the disease-free survival (DFS) benefit of adjuvant chemotherapy for breast cancer patients with resected isolated locoregional recurrences (ILRRs) that are estrogen receptor (ER)-negative and rules out its use in the ER-positive scenario.
Stefan Aebi (Lucerne Cantonal Hospital, Switzerland) and fellow investigators explain that “the risk of distant metastases and death is high” after the occurrence of an ILRR, but that disease recurrence may be delayed with adjuvant chemotherapy, with a prior analysis of the trial at a median of 5 years showing a significant benefit for patients with ER-negative ILRRs, although the findings were “uncertain” for the ER-positive subset.
The current analysis – conducted at a median of 9 years – helps to clarify the situation, showing a significant DFS improvement with the receipt of adjuvant chemotherapy in the subset of 58 participants with an ER-negative ILRR, at a hazard ratio (HR) of 0.29, but no difference between the chemotherapy and control arms for the 104 patients with an ER-positive ILRR, with a nonsignificant HR of 1.07.
In the ER-negative subgroup, the 10-year DFS rates were 70% for the chemotherapy arm versus 34% for the no chemotherapy arm, while the corresponding rates in the ER-positive cohort were 50% and 59%.
The phase III trial enrolled patients with a completely resected ILRR and randomly assigned them to receive an adjuvant chemotherapeutic regimen of the physician’s choice or no chemotherapy. Participants with hormone receptor-positive disease received adjuvant endocrine therapy, and radiotherapy was mandated for those with microscopically involved margins.
Similar to the DFS results, adjuvant chemotherapy was also associated with a significant improvement in the breast cancer-free interval among participants with ER-negative, but not ER-positive, ILRRs. However, overall survival was not significantly prolonged with chemotherapy in either subgroup.
Of note, the interaction between ER status and chemotherapy efficacy was significant when the ER status in question was that of the ILRR, but this was not the case when the profile of the primary tumor was considered, suggesting that “patients with an ILRR should be managed according to the endocrine molecular profile of the recurrent cancer and not the primary cancer,” the CALOR investigators comment in the Journal of Clinical Oncology.
The authors of a related editorial say that “for patients with ER-negative [ILRR], the uncertainty regarding the role of chemotherapy has now been resolved, and chemotherapy should be offered as standard of care in addition to surgical resection and radiation for such patients.”
However, owing to a low accrual rate – “because ILRR is not a common occurrence” – the sample size was smaller than originally planned, and the study “may not have been adequately powered to exclude a benefit in the subgroup of patients with ER-positive disease,” they note.
Nancy Chan and Deborah Lynn Toppmeyer, both from the Rutgers Cancer Institute of New Jersey in New Brunswick, USA, continue: “Therefore, one cannot draw the definitive conclusion that there is no potential benefit in the ER-positive subgroup, especially in the luminal B molecular subtype.”
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