Abstract LBA4 – OS KEYNOTE-522

Arguably one of the most anticipated presentations at ESMO 2024 featured the overall survival (OS) data of the pivotal phase III KEYNOTE-522 trial. Based on a convincing benefit in event-free survival (EFS), this trial established the combination of neoadjuvant chemotherapy with pembrolizumab followed by surgery and adjuvant pembrolizumab as a new standard of care for patients with early-stage triple negative breast cancer (TNBC). In this video, Dr Elisa Agostinetto (Institut Jules Bordet, Brussel) meets up with Prof Dr Peter Schmid (Barts Cancer Center) who presented these long-awaited data as part of the presidential session at ESMO 2024.

In KEYNOTE-522, a total of 1,174 patients with newly diagnosed, non-metastatic TNBC (T1c, N1-2 or T2-4, N0-2) were randomly assigned to be treated with neoadjuvant chemotherapy (4 cycles of carboplatin-paclitaxel followed by 4 cycles of doxorubicin/epirubicin + cyclophosphamide) in combination with pembrolizumab, followed by surgery and adjuvant pembrolizumab, or neoadjuvant chemotherapy and surgery alone. As reported earlier, KEYNOTE-522 convincingly met its two primary endpoints by showing a superior rate of pathological complete response (pCR) and a significantly longer event-free survival (EFS) for patients treated with the pembrolizumab-containing regimen.

After a median follow-up 75.1 months, it was clear that the significant benefit in EFS translated into a significantly better OS for patients treated with pembrolizumab (HR[95%CI]:0.66[0.50-0.87], p= 0.0015). At the 5-year landmark, 86.6% of patients in the pembrolizumab arm were still alive, which is 4.9% more than in the control arm. Importantly, this OS benefit was observed regardless of whether the patient obtained a pCR at the end of the neoadjuvant therapy or not (HR for OS 0.69 and 0.76 for patients with and without a pCR). The benefit of pembrolizumab on OS also proved to be consistent irrespective of the level of PD-L1 expression and the nodal status of patients.

Finally, the long-term data of KEYNOTE-522 solidified the previously reported findings on EFS. After 5 years, 81.2% of patients in the pembrolizumab arm were event free as compared to 72.2% in the control arm (HR[95%CI]: 0.65[0.51-0.83]). With respect to safety, the longer follow-up did not reveal any new findings.