Neoadjuvant Nivolumab Plus Carboplatin/Paclitaxel Elicits High pCR Rates in Early-Stage TNBC

Neoadjuvant nivolumab (Opdivo) and non–anthracycline containing chemotherapy produced promising pathologic complete response (pCR) rates regardless of whether nivolumab was administered before or during treatment with carboplatin and paclitaxel in patients with stage I to IIB 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.¹

At a median follow-up of 12 months, the pCR rate in the nivolumab lead-in arm was 51% (90% CI, 39%-63%) vs 54% (90% CI, 43%-66%) with concurrent administration, for an overall pCR rate of 53% (90% CI, 44%-61%).

“pCR rates exceeding 50% support a 12-week neoadjuvant non-anthracycline chemotherapy regimen with nivolumab for stage I/II 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 II/III TNBC. However, not all patients need to receive all components of the phase 3 KEYNOTE-522 regimen (NCT03036488). Notably, findings from the phase 2 GeparNuevo trial (NCT02685059) demonstrated higher pathologic complete response rates with an immunotherapy lead-in vs concurrent chemoimmunotherapy, at 61% vs 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.

The non-comparative, Simon 2-stage design was evaluated pCR, defined as ypT0/is or ypN0 greater than 40%. Secondary end points included residual cancer burden, safety, pCR by PD-L1 status (≥1% per the SP-142 assay) and tumor-infiltrating lymphocytes (TILs; ≥30%), and event-free survival (EFS). Adjuvant chemotherapy was allowed per investigator decision.

Eligible patients had primary stage I (cT1c cN0), IIA (cT1 cN1; cT2 cN0), or IIB (cT2 cN1; cT3 cN0) TNBC. Patients were randomly assigned to receive 360 mg of nivolumab and carboplatin at area under the curve 5 on day 1 every 3 weeks for 4 cycles, plus 80 mg/m2 of paclitaxel on days 1, 8, and 15 every 3 weeks for 4 cycles. This was administered with (n = 53; arm A) or without (n = 55; arm B) a 2-week lead-in of 240 mg of nivolumab. Patients in arm B received the nivolumab lead-in after completing the 4 cycles of chemoimmunotherapy. Fourteen to twenty-eight days after the last dose of paclitaxel and nivolumab, 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 (26% in arm A; 16% in arm B). Most patients were pre/perimenopausal (53%; 55%), had stage II/III disease (66%; 65%), and median Ki67 expression (70%; 70%). TIL 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% vs 46% in arms A and B, respectively (odds ratio, 2.47).

“[The regimen] was well tolerated, with no new safety signals seen,” the authors concluded.

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

Disclosures: Dr Zdenkowski reported the following financial relationships: employment with Breast Cancer Trials (ANZ); consultant for Lilly, Eisai, AstraZeneca, MSD, and Novartis; speaker’s bureau for Nil; grant/research support from Pfizer, Roche, GSK, Novartis, Lilly, and BMS; stockholder in Nil; and honoraria from Roche, Pfizer, Eisai, Amgen, Gilead, Novartis, Lilly, and AstraZeneca.

Reference

Randomized phase II study of neoadjuvant nivolumab (n) monotherapy 2 week lead-in followed by 12 weeks of concurrent n+carboplatin plus paclitaxel (cbp) vs concurrent n+cbp in triple negative breast cancer (TNBC): (BCT1902/IBCSG 61-20 Neo-N). Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract LBAO1-03.