253P - Is 6-weekly administration of pembrolizumab in combination with chemotherapy for early triple-negative breast cancer safe? A real-world early comparison of q6w versus q3w administration of pembrolizumab in two large cancer centres in the UK

Background

The KEYNOTE 522 regimen is now established as the gold standard for patients with at least T2N0 or N+ early triple-negative breast cancer. In KEYNOTE 522, Pembrolizumab was administered every 3 weeks at 200mg. Following approval of 6-weekly administration by the FDA and EMA, hospitals could choose to implement q6w (400mg) or q3w (200mg) administration of Pembrolizumab. On implementation of q6w Pembrolizumab at St Bartholomew's Hospital (SBH), we observed a higher-than-expected rate of grade 3-4 hepatotoxicity. This led to this real-world retrospective study, comparing our rates of toxicity with those seen at Guys Cancer Centre using the q3w regime.

Methods

We identified 21 eligible patients treated at SBH, who received at least one of cycle of q6w Pembrolizumab and 17 patients who received it q3w at GSTT from November 2022 – March 2023. Epidemiological and clinical data were collected retrospectively.

Results

In KEYNOTE 522, grade 3-5 transaminitis was seen in 5.5% of patients receiving Pembrolizumab. Of the 21 patients receiving q6w Pembrolizumab at SBH, there was a higher frequency of grade 3 transaminitis (Table). All 4 patients (19%) with G3 transaminitis required hospitalisation for IV steroids, with 2 developing grade 4 hyperbilirubinaemia requiring additional immunosuppression. A liver biopsy was carried out with 1 of 2 patients demonstrating vanishing bile duct syndrome. Pembrolizumab was discontinued in all 4 patients and 1 patient had to discontinue chemotherapy. In comparison, patients who received q3w Pembrolizumab at GSTT experienced no grade 3 toxicities. Table: 253P

Conclusions

Although this study is limited by short follow-up and small number of patients it suggests that administration of q6w Pembrolizumab may be associated with a higher risk of grade 3 immune related hepatotoxicity. Further studies are required to confirm these findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

V. Angelis: Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Novartis. C. Gousis: Financial Interests, Personal, Invited Speaker: Pfizer, Kinks Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Personal Mind Medicine; Non-Financial Interests, Personal, Training: AstraZeneca. P.E. Hall: Financial Interests, Personal, Invited Speaker: Eisai, Pfizer, MSD, Gilead, Seagen; Financial Interests, Personal, Advisory Board: Novartis. M. Nathan: Financial Interests, Personal, Invited Speaker: AstraZeneca, Lilly, Pfizer, MSD. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Gilead, Eisai, MSD, Seagen, Amgen, Celgene, Lilly; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. M. Phillips: Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Eisai, Gilead; Non-Financial Interests, Personal, Invited Speaker: Seagen. All other authors have declared no conflicts of interest.