Treatment toxicities and pathological response through the evolution of neoadjuvant regimens in early triple-negative...

Pembrolizumab-based neoadjuvant chemoimmunotherapy (CIT) is the new standard of care for high-risk early triple-negative breast cancer (eTNBC). The addition of multiple cytotoxic drugs can lead to cumulative toxicities. We report the evolution of chemotherapy (CT) practice and its impact on completion and effectiveness of subsequent regimens in a real-world setting.

We conducted an ambispective, observational study of patients with eTNBC at a comprehensive cancer centre between February 2019 and February 2024. All data were extracted from electronic health records and manually curated.

Of the 366 patients enrolled, 247 received neoadjuvant CT and 119 received CIT. Grade 3/4 toxicities were more common in the CIT group (78.2% versus 58.6%, P < 0.001). The most common adverse events in both groups were haematological, gastrointestinal and general health deterioration [e.g. moving from Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 to ECOG PS 2-4]. In the CIT group, 56.8% of patients experienced at least one immune-related adverse event, 11.3% of which were grade 3/4. Toxicities led to a significantly higher rate of dose reductions (48.7% versus 25.0%, P < 0.0001), treatment delays (65.2% versus 27.5%, P < 0.0001) or permanent discontinuation (31.1% versus 16.0%, P < 0.001) in the CIT cohort. The pathological complete response (pCR) rate was significantly increased to 68.4% in the CIT group versus 51.9% in the CT group (P < 0.01). No effect of toxicities or dose adjustments on the pCR rate was observed in either group.

Escalation of neoadjuvant CIT in TNBC increases toxicity and leads to significant dose reductions without affecting the improvement in pCR rate.