Daily highlight in early stage breast cancer

Prof Neven from KU Leuven reports on the proferred papers on early stage Breast Cancer that were reported the first day of the congress.

The first presentation by Prof Nadia Harbeck is an update of the monarchE, focusing on patients with high-risk early-stage breast cancer with positive lymph nodes (either more than four or between one and three), along with a tumour size exceeding five centimetres or a 3×3 cm tumour. The interim analysis after five years reveals a persistent benefit in invasive disease-free survival, surpassing previous interim analyses.

The next two presentations are on studies that have already earlier published data. The first study, presented by Peter Schmid, was the Keynote 522 trial, a neo-adjuvant treatment study in patients with triple-negative breast cancer. After a five-year follow-up, there’s a persistent benefit in EFS, with an event-free survival rate improvement of 10 per cent. The next neo-adjuvant study involving immune treatment was the NeoTRIP trial, presented by Luca Gianni. Unfortunately, this study yielded negative results. It’s worth noting that, unlike Keynote 522, with almost 1200 patients, the NeoTRIP trial involved only 250 patients, and these patients were not only early-stage but also locally advanced non-metastatic. The addition of the immune checkpoint inhibitor, atezolizumab (as opposed to pembrolizumab in Keynote 522), did not show any significant difference. Atezolizumab has a distinct mechanism of action, targeting the PDL1 on tumour cells rather than the PD1 on T cells, which might explain the differences. Luca Gianni mentioned a biomarker they studied and published in Nature to identify patients who might benefit more.

The last two presentations were two pivotal studies on neo-adjuvant immune checkpoint inhibitors in patients with hormone receptor-positive, HER2-negative breast cancer. The first, the CheckMate 7LF study, led by Shereen Loi from Australia, aimed to recruit 500 patients but faced challenges due to the COVID-19 pandemic. This trial demonstrated a substantial improvement in the PCR rate in ER-positive HER2-negative breast cancer by adding nivolumab to the chemotherapy regimen, doubling the PCR rate from 13% to 25%. The second neoadjuvant clinical study was presented by Fatima Cardoso from Portugal, featuring the Keynote 756 database, with over 1,000 patients. This study also utilised pembrolizumab for ER-positive, HER2-negative breast cancer patients. The addition of pembrolizumab to neoadjuvant chemotherapy led to a doubling of the PCR rate, although there were no significant differences across different subgroups, including PDL1 status. Again, a longer follow-up period is required to determine the clinical impact of this trial.

These findings indicate a potential role for immune checkpoint inhibitors in ER-positive, HER2-negative breast cancer, a tumour type traditionally considered “cold.” Patient selection and further investigation will be crucial, particularly as the participants likely had high-grade lesions, potentially representing a subset of luminal B-like breast cancer patients.

References

Nadia Harbeck – Adjuvant abemaciclib plus endocrine therapy for HR+, HER2-, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes.  ESMO 2023 – LBA17 

Peter Schmid –  Pembrolizumab or placebo plus chemotherapy followed by pembrolizumab or placebo for early-stage TNBC: Updated EFS results from the phase 3 KEYNOTE-522 study – ESMO 2023 LBA18

Luca Gianni – Event-free survival (EFS) analysis of neoadjuvant taxane/carboplatin with or without atezolizumab followed by an adjuvant anthracycline regimen in high-risk triple negative breast cancer (TNBC): NeoTRIP Michelangelo randomized study – ESMO 2023, LBA19

Shereen Loi – A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC) – ESMO 2023, LBA20

Fatima Cardoso – KEYNOTE-756: Phase 3 study of neoadjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo), followed by adjuvant pembro or pbo + endocrine therapy (ET) for early-stage high-risk ER+/HER2– breast cancer – ESMO 2023, LBA 21