Abstract 1821P
Background
Pembrolizumab is an anti-PDL1 immune checkpoint inhibitor licenced across a variety of tumour sites. The dosing schedule was 200mg 3 weekly (q3w). In April 2019 the European Commission approved 400mg 6 weekly (q6w) dosing based on simulation of dose/exposure relationships and predicted no difference in toxicity. The lack of clinical data supporting this has, however, raised concern amongst clinicians. We therefore retrospectively analysed toxicity data for the q3w and q6w schedules.
Methods
All patients who received Pembrolizumab for any indication between March-December 2019 were included across three regional centres. Toxicity data was collected retrospectively using Common Terminology Criteria for Adverse Events v5.0. Clinically significant immune-related adverse events (CSirAE) were defined as immune-related events and ≥grade 3 rash. Data was analysed using incidence (Poisson distribution) and incidence ratio.
Results
63 patients started on q6w and 110 patients received q3w. Group characteristics are summarised in the table. There were a total of 11 grade 3-5 CSirAE (3 for q6w and 8 for q3w) and 44 grade 1-2 CSirAE (13 for q6w and 31 for q3w). The incidence of any-grade CSirAE per 100 patient-months (95% CI) was 4.09 (1.77-5.68) for q6w and 3.32 (2.36-4.54) for q3w with an incidence ratio of 1.23 (0.64 – 2.26). The incidence of grade 3-5 CSirAE was 0.77 (0.16-2.24) in q6w and 0.68 (0.29-1.34) in q3w with an incidence ratio of 1.13 (0.19 – 4.70). Both groups had a high proportion of patients with low grade toxicity (fatigue, pruritus, rash; q6w 46%, q3w 42%). Table: 1821P
Group characteristics (median, range)
| q6w | q3w | |
| Age (yr) | 72 (33-90) | 72 (42-91) |
| Follow-up time (months) | 6.2 (0.1-11) | 13.2 (2.5-44) |
| Treatment cycles given | 4 (1-10) | 14 (3-57) |
| Total treatment duration (patient-months) | 391 | 1175 |
Conclusions
To our knowledge, this is the first analysis of toxicity data for a q6w Pembrolizumab regime. Incidence of CSirAEs is low. Low grade toxicity was common and over the course of treatment could impact quality of life. Despite limited number of events, the q6w schedule does not appear to lead to significantly higher toxicity and should be used in view of the reduced visit burden to patients and health services.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
the authors.
Funding
Has not received any funding.
Disclosure
M.P. Rowe: Travel/Accommodation/Expenses: Astellas Pharma. T. Talbot: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck,Sharpe&Dome; Bristol Myers Squibb; Roche; Novartis. All other authors have declared no conflicts of interest.