medwireNews: The addition of durvalumab and olaparib to neoadjuvant chemotherapy is associated with improved pathologic complete response (pCR) in women with stage II or III HER2-negative breast cancer, show data from the I-SPY 2 trial.
As reported by Lajos Pusztai (Yale University, New Haven, Connecticut, USA) at the 2020 AACR Virtual Annual Meeting I, the estimated pCR rate was 37% for the 73 participants who received three doses of neoadjuvant durvalumab 1500 mg every 4 weeks plus olaparib 100 mg twice daily during weeks 1–11 alongside weekly paclitaxel 80 mg/m2 for 12 weeks, followed by four cycles of doxorubicin and cyclophosphamide.
This was higher than the 20% estimated pCR rate for the 299 control participants who received just the chemotherapy regimen of paclitaxel and subsequent doxorubicin plus cyclophosphamide.
Interview: I-SPY 2 researcher Lajos Pusztai discusses the main results reported at AACR 2020.
Explaining that the phase 2 I-SPY 2 study uses response-adaptive randomization to test several regimens against a common control arm, Pusztai noted that the Bayesian predictive probability of the combination of durvalumab, olaparib, and chemotherapy outperforming the control in a phase 3 trial comprising 300 patients was 81%, which met the threshold for “graduation with success.”
He also reported pCR rates by subgroup, noting that the triplet regimen appeared to benefit patients regardless of hormone receptor (HR) status. Specifically, among the 52 HR-positive patients, the estimated pCR rates were 28% for the triplet regimen versus 14% for the control, with corresponding rates of 47% and 27% for the 21 HR-negative (ie, triple-negative breast cancer) patients.
Pusztai added that a prespecified biomarker analysis showed further differences in the HR-positive patients, all of whom needed to have a high-risk MammaPrint score to meet the trial’s eligibility criteria. Interestingly, the benefit afforded by the triplet regimen appeared to be restricted to women with ultra-high-risk scores (defined as above the median observed in the I-SPY 1 trial), with an estimated pCR rate of 64% versus 22% for chemotherapy alone.
By contrast, the estimated pCR rates were comparable for the triplet and control therapies among women who did not have ultra-high-risk scores, at 9% and 10%, respectively.
In terms of the safety profile, “there were no unexpected safety signals and adverse events [AEs] were consistent with known side effects,” said Pusztai.
AEs of grade 3 or 4 occurred in 58.0% of participants given the triplet regimen and 41.0% of those given chemotherapy alone, and the rates of grade 3 immune-related AEs were 19.0% and 1.6%, respectively.
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