Presurgical Opdivo, Chemo See High Response in Early-Stage Breast Cancer

Neoadjuvant (administered before surgery) Opdivo (nivolumab) and non–anthracycline containing chemotherapy produced promising pathologic complete response (pCR; the disappearance of cancer) rates regardless of whether Opdivo was administered before or during treatment with carboplatin and paclitaxel in patients with stage 1 to 2B triple-negative breast cancer (TNBC), according to findings from the phase 2 BCT1902/IBCSG 61-20 Neo-N trial presented at the 2023 San Antonio Breast Cancer Symposium.

At a median follow-up of 12 months, the pCR rate in the Opdivo lead-in arm was 51% versus 55% with concurrent administration, for an overall pCR rate of 53%.

“pCR rates exceeding 50% support a 12-week neoadjuvant non-anthracycline chemotherapy regimen with (Opdivo) for stage 1/2 TNBC,” the study authors wrote in their presentation.

Neoadjuvant systemic therapy with checkpoint inhibition is a standard of care in the treatment of patients with stage 2/3 TNBC. However, not all patients need to receive all components of the phase 3 KEYNOTE-522 regimen. Notably, findings from the phase 2 GeparNuevo trial demonstrated higher pathologic complete response rates with an immunotherapy lead-in versus concurrent chemoimmunotherapy, at 61% versus 38%, respectively.

The belief that immune enriched tumors may derive greater benefit from immunotherapy coupled with the notion that pCR is associated with good prognosis led investigators to evaluate a de-escalated chemotherapy approach in patients with TNBC.

Eligible patients had primary stage 1, 2A or 2B TNBC. Patients were randomly assigned to receive 360 mg of Opdivo and carboplatin at area under the curve 5 on day 1 every three weeks for four cycles, plus 80 mg/m2 of paclitaxel on days 1, 8 and 15 every three weeks for four cycles. This was administered with (arm A, 53 patients) or without (arm B, 55 patients) a two-week lead-in of 240 mg of Opdivo. Patients in arm B received the Opdivo lead-in after completing the four cycles of chemoimmunotherapy. Fourteen to 28 days after the last dose of paclitaxel and Opdivo, respectively, patients proceeded to surgery.

The study enrolled 110 patients, 108 of whom were evaluable, across 14 centers between July 2020 and April 2022. In both arms, the majority of patients were 40 years of age or above. Most patients were pre/perimenopausal (53%; 55%), had stage 2/3 disease (66%; 65%) and median Ki67 expression (70%; 70%). TIL (tumor-infiltrating lymphocyte) expression of at least 30% was present in 34% of patients in the lead-in arm and 33% of those in the concurrent arm; PD-L1 positivity was present in 43% and 51% of tumors, respectively.

Additional findings indicated that high TIL expression was the only predictor of pCR in a multivariable logistic regression model that accounted for age, study cohort, stage and TILs. pCR rates in patients with high TILs were 67% versus 46% in arms A and B, respectively.

“(The regimen) was well-tolerated, with no new safety signals seen,” the authors concluded.

EFS results are still maturing, and translational research is ongoing.

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