Patients with triple-negative breast cancer (TNBC) and more than 40% tumour-infiltrating lymphocytes (TIL) responded well to neoadjuvant immune checkpoint blockade, results from the phase 2 BELLINI trial showed.
High TIL levels correlate with a good prognosis in early TNBC [1,2]. In patients with early TNBC, the combination of neoadjuvant chemotherapy with PD immune checkpoint-blocking agents increased the pathological complete response (pCR) and event-free survival [3,4]. However, it is not known which TNBC patients specifically benefit from neoadjuvant PD1 inhibition, for which patients’ neoadjuvant chemotherapy can be de-escalated, or whether there is an additional value of other (new generation) immune checkpoint inhibitors. Prof. Marleen Kok (Netherlands Cancer Institute, the Netherlands) presented the first stage I findings of the phase 2 basket trial BELLINI (EudraCT 2018-004188-30) testing the hypothesis that there is a subset of TNBC patients with highly immunogenic tumours and that TIL levels (at baseline) can help identify this subset .
BELLINI is a non-randomised window-of-opportunity study with baskets for nivolumab and nivolumab plus ipilimumab. Each basket included at least 15 participants with stage I–III TNBC (T1c–T3, N–/N+, TIL ≥5%), divided into 3 TIL categories (at least 5 participants per category): TIL-low (5–10% TIL), TIL- intermediate (11–49% TIL) and TIL-high (≥50% TIL). Participants were treated with nivolumab (2 cycles, n=16) or nivolumab/ipilimumab (2 cycles nivolumab, 1 cycle ipilimumab, n=15) before the start of neoadjuvant chemotherapy or surgery. The primary endpoint was immune activation, defined as a 2-fold change in CD8-positive T cells or a 2-fold increase in IFN-γ expression after 4 weeks. The secondary endpoints included safety and radiological responses.
At 4 weeks, 3/19 (19%) participants treated with nivolumab and 4/15 (27%) participants treated with nivolumab/ipilimumab showed a partial radiological response. Of these 7 responders, 3 were TIL-high and 4 were TIL-intermediate. All responders had >40% TIL. No responses were observed in TIL-low participants. Most biopsies of patients with a partial radiological response were free from tumour cells, illustrating pCR, after 4 weeks. A 2-fold increase of CD8-positive T cells was observed in 53.3% of nivolumab-treated participants and 60% of nivolumab/ipilimumab-receiving participants. Both cohorts met the primary endpoint, encouraging the progression to stage II of the trial.
Radiological responders and non-responders were discriminated by a significant difference in both the levels of IFN-γ expression (higher in responders, P=0.014) and spatial distribution of CD8-positive T cells (closer to tumour cells in responders, P=0.0014). For all patients showing a partial response on MRI, circulating tumour DNA at 4 weeks was either cleared or <50% of baseline measurements.
“The majority of TNBC patients with TIL showed increased immune activation after only 4 weeks of immune checkpoint blockade and a substantial fraction of these patients experienced a clinical response, highlighting the potential of immune checkpoint blockade without chemotherapy for TNBC patients,” concluded Prof. Kok.
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- De Jong VMT, et al. J Clin Oncol. 2022;40(21):2361–2374.
- Mittendorf EA, et al. Lancet. 2020;396(10257):1090–1100.
- Schmid P, et al. N Engl J Med. 2022;386(6):556–567.
- Nederlof I, et al. Nivolumab and ipilimumab in early-stage triple-negative breast cancer (TNBC) with tumour-infiltrating lymphocytes (TILs): First results from the BELLINI trial. Abstract LBA13, ESMO Congress 2022, 09–13 September, Paris, France.
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Table of Contents: ESMO 2022
Letter from the Editor
High pathological responses to neoadjuvant immune checkpoint inhibition in locally advanced dMMR colon cancer
Fruquintinib: a potential new treatment for patients with refractory mCRC
Second-line avelumab is effective in patients with MSI-H/dMMR mCRC
Upper Gastrointestinal Cancer
Deep learning models predict the risk of relapse and the mutational profile in GIST
Addition of pembrolizumab to lenvatinib does not improve OS in advanced HCC
New, highly selective inhibitor of FGFR2 driver alterations and resistance mutations
Chemo-immunotherapy in gastric cancer is more effective when administered in parallel
Tumour infiltrating lymphocytes identify patients with immunogenic triple-negative breast cancer
OS benefit of abemaciclib in HR-positive/HER2-negative advanced breast cancer not (yet) statistically significant
OS benefit of sacituzumab govitecan in pre-treated HR-positive/HER2-negative metastatic breast cancer
A pathway from air pollution to lung cancer in non-smokers identified
Selective KRASG12C inhibitor sotorasib demonstrates superior PFS and ORR compared to docetaxel in previously treated patients with NSCLC
Promising clinical activity of tepotinib plus osimertinib in NSCLC with MET amplification after progression on first-line osimertinib
High pathological responses in borderline resectable NSCLC patients after induction with dual immunotherapy and concurrent chemoradiotherapy
Treatment with tumour-infiltrating lymphocytes for advanced melanoma outperforms ipilimumab
Neoadjuvant pembrolizumab outperforms adjuvant pembrolizumab in resectable stage III–IV melanomas
Survival-benefit of neoadjuvant T-VEC maintained over 5 years of follow-up
Baseline ctDNA predicts survival in resected stage III–IV melanoma
Genitourinary Cancer – Prostate Cancer
Overall survival benefit of abiraterone in mHSPC is maintained for 7 years
Limited benefit of adding long-term ADT to post-operative radiotherapy in prostate cancer
Intensified ADT benefits biochemical progression-free survival in biochemically relapsed prostate cancer
Genitourinary Cancer – Non-Prostate Cancer
Adjuvant nivolumab plus ipilimumab does not improve survival in patients with localised RCC at high risk of relapse after nephrectomy
Triple therapy improves progression-free survival in patients with advanced RCC versus dual therapy
Adjuvant atezolizumab does not improve outcomes for patients with RCC and increased risk of recurrence
OS benefit for advanced ovarian cancer patients treated with maintenance olaparib
Maintenance tegafur-uracil does not improve survival in locally advanced cervical cancer
Head and Neck Cancer
Adding first-line pembrolizumab to CRT in locally advanced HNSCC does not significantly prolong survival or event-free survival
5-FU-free chemotherapy combination as an alternative for first-line treatment of recurrent or metastatic HNSCC
Epstein Barr virus-specific autologous cytotoxic T lymphocytes do not improve survival in nasopharyngeal carcinoma