Residual cancer burden may predict treatment efficacy in breast cancer
medwireNews: Residual cancer burden (RCB) offers prognostic information after neoadjuvant chemotherapy across breast cancer subtypes and treatments, show data from I-SPY2.
Laura Esserman (University of California, San Francisco, USA) and co-authors explain that I-SPY2 is a multicenter adaptive trial, which enables concurrent evaluation of novel neoadjuvant treatment combinations relative to a common taxane–anthracycline-based chemotherapy control in women with stage II or III breast cancer at high risk for early recurrence.
Of the 938 women (mean age, 49 years; 80% White) included in the current analysis, based on the first 10 investigational treatments evaluated, 38% had a hormone receptor-positive (HR+)/HER2-negative (–) subtype, 34% were HR–/HER2–, 18% were HR+/HER2+, and 9% were HR–/HER2+.
The researchers found that, following treatment, the RCB distribution, which ranges from RCB-0 (equivalent to pathologic complete response [pCR]) to RCB-III (indicating a higher level of residual disease), varied among the breast cancer subtypes. For example, individuals with HR–/HER2+ disease had the highest proportion of RCB-0 scores, at around 68%, whereas those with HR+/HER2– disease had the lowest proportion, at approximately 18%.
Despite these differences, Cox regression analyses showed that event-free survival worsened significantly with increasing RCB in all four breast cancer subtypes. The risk for locoregional recurrence, distant recurrence, or death during a median 52 months of follow-up increased by a significant 1.55- to 2.39-fold, depending on the subtype, with each unit increase in RCB.
As part of the trial, treatments that have an 85% or greater probability of improving pCR rates graduate to larger, confirmatory trials. However, Esserman and team showed that RCB offered similar prognostic information regardless of whether or not a treatment graduated. In this case, each unit increase in RCB was associated with significant 2.00, 1.87, and 1.79 times increased risks for recurrence or death with graduated, non-graduated, and control treatments, respectively.
Of note, 21% of participants received neoadjuvant chemotherapy in the control arm, 27% received an investigational therapy that graduated in their subtype of breast cancer, and 52% received an investigational therapy that did not graduate in their subtype.
Finally, the investigators observed that “[t]he graduated regimens reduced the proportion of patients with high RCB values that are associated with greatest residual prognostic risk, and this could potentially improve the survival effect of a new treatment even more than converting other patients from lower RCB values to pCR.”
The team concludes in JAMA Oncology that their “results suggest that RCB after neoadjuvant chemotherapy is a robust prognostic response measure across treatments and within subtypes and, when compared between randomized treatments, is likely to be a clinically useful measure of efficacy.”
The next step will be “to evaluate RCB in additional randomized clinical trials to further refine the use and interpretation of shifts in RCB distribution from individual treatment regimens,” they add.
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