High pCR rates with dual neoadjuvant immunotherapy in TIL-high TNBC

Two cycles of dual neoadjuvant immunotherapy (nivolumab/ipilimumab or nivolumab/relatlimab) induced high pathologic response rates (pCR) in patients with triple-negative breast cancer (TNBC) harbouring high numbers of tumour-infiltrating T cells (TILs) in two cohorts of the phase 2 BELLINI trial.

PD-1 inhibition added to neoadjuvant chemotherapy has recently shown to improve survival in early TNBC patients [1]; however, this comes with substantial toxicity. On the other hand, patients with TNBC and high levels of TILs have excellent survival even without chemotherapy, while in other solid tumours, combination checkpoint blockade showed favourable outcomes compared with anti-PD1 monotherapy [2,3].

The phase 2 BELLINI trial (NCT03815890) aimed to evaluate the efficacy of neoadjuvant immunotherapy combinations in patients with TIL-high TNBC. Dr Iris Nederlof (Netherlands Cancer Institute, the Netherlands) presented results from 2 combination cohorts: nivolumab/ipilimumab and nivolumab/relatlimab [4]. Both cohorts enrolled 15 participants (TILs ≥50%) who received either 2 cycles of nivolumab/ipilimumab every 3 weeks followed by resection 6 weeks after the start of the therapy or 2 cycles of nivolumab/relatlimab every 4 weeks followed by resection 8 weeks after the start of the therapy. The primary endpoint of the study was pCR.

In the nivolumab/ipilimumab cohort, 5 participants obtained pCR (33%) and 3 obtained near pCR, resulting in a rate of 53% obtaining major pathological response (MPR), a secondary endpoint. In the nivolumab/relatlimab cohort, 7 participants obtained pCR (47%) and 4 obtained near pCR, so the MPR rate was 73% (see Figure). In both cohorts, neoadjuvant dual immunotherapy came with a high incidence of immune-related adverse events (100% any grade, 40–47% grade 3–4), including hypothyroidism, adrenal gland insufficiency, and hepatitis. No delay of surgery was observed in either cohort.

Figure: Pathological response with nivolumab/relatlimab in BELLINI [4]



“These promising pCR rates met the threshold to expand our cohorts to stage II. However, the high rates of immune-related adverse events need further research on the quality-of-life effect of these therapies,” Dr Nederlof concluded.

1. Schmid P, et al. N Engl J Med 2024;Sept 15. DOI: 10.1056/NEJMoa2409932.
2. Geurts VCM, et al. JAMA Oncol. 2024;10:1077-1086.
3. Tawbi HA, et al. N Engl J Med 2022;386:24-34.
4. Nederlof I, et al. Neoadjuvant nivolumab/relatlimab or nivolumab/ipilimumab in triple negative breast cancer with high tumor-infiltrating lymphocytes (TILs). Abstract LBA11, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024