High pCR with neoadjuvant nivolumab/chemotherapy in stage I–II TNBC

A 12-week neoadjuvant, non-anthracycline chemotherapy regimen with nivolumab induced pathological complete response (pCR) rates over 50% in patients with stage I–II triple-negative breast cancer (TNBC), as was shown in a phase 2 Australian study.

For patients with stage II–III TNBC, neoadjuvant systemic therapy including immunotherapy is standard-of-care [1]. However, the optimal neoadjuvant regimen is not yet clear for all patients. Results from the GeparNuevo trial (NCT02685059) showed a higher pCR with a 2-week neoadjuvant immunotherapy ‘lead-in’ versus concurrent neoadjuvant chemo/immunotherapy [2]. Furthermore, the addition of immune checkpoint inhibition may allow shorter chemotherapy duration in selected patients.

The BCT1902/IBCSG 61-20 Neo-N trial aimed to investigate the strategies of a lead-in nivolumab monotherapy followed by chemotherapy versus concurrent nivolumab and chemotherapy. This phase 2 study enrolled 108 patients with stage I–IIB TNBC and randomised them 1:1 to receive either 1 dose of nivolumab followed 2 weeks later by nivolumab plus carboplatin/paclitaxel for 4 cycles (arm A) or 4 cycles of nivolumab plus carboplatin/paclitaxel followed by 1 dose of nivolumab, prior to surgery. The primary endpoint was pCR (ypT0/Tis ypN0). Dr Nicholas Zdenkowski (University of Newcastle, Australia) presented the first results [3].

No evidence was observed for differences in pCR rate between arms: 51% in arm A versus 55% in arm B. Multivariable logistic regression showed that high levels of tumour-infiltrating lymphocytes (TILs) might be a predictor of pCR (67% in high TILs vs 46% in low TILs; OR 2.47). In addition, expression of PD-L1 (≥1% SP-142) was associated with high pCR (71% in PD-L1 positive vs 33% in PD-L1 negative tumours).

“pCR rates in this study exceeded 50%, supporting a 12-week neoadjuvant, non-anthracycline chemotherapy regimen with nivolumab for patients with stage I–II TNBC. Patients with immune-enriched tumours, identified by high TILs or PD-L1 expression, had high pCR rates with just 12 weeks of treatment. However, this study did not support the hypothesis that lead-in nivolumab is associated with a pCR advantage,” concluded Dr Zdenkowski. Event-free survival results are still immature.

1. Curigliano G, et al. Ann Oncol. 2023;34:970-986.
2. Loibl S, et al. Ann Oncol. 2019;30:1279-1288.
3. Loi S, et al. Randomized phase II study of neoadjuvant nivolumab (N) 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). Abstract LBO1-03, SABCS 2023, 5–9 December, San Antonio, TX, USA.

 

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Posted on 11 January, 202425 March, 2024