Complete responders to anti-PD1 antibodies. What happens when we stop?

Background

PD-1 antibodies are now recognized as a standard therapy for advanced melanoma. The optimal duration is unknown, with initial trials ceasing therapy on progression or intolerance. Subsequent trials have had a pre-defined stopping point of 2 years of therapy. Within trials with Pembrolizumab there has also been the potential to cease therapy after 6 months if the patient is a complete responder (CR). The data from these trials and the number of patients (pts) who stopped for CR has not been reported. In practice pts often request to cease therapy after CR, this is the first report of a cohort of pts who has chosen to do this.

Methods

A retrospective review was conducted of CR to PD-1 based therapy across 2 institutions from a single prescriber. Pts were from Pembrolizumab Named Patient Program (PEM NPP), Nivolumab monotherapy (NIVO) and reimbursed Pembrolizumab (r PEM). To be eligible, pts had to have experienced a CR to PD-1 based therapy and ceased therapy because of this. Data were included from pts including assessments of select (immune-related) adverse events, time to onset of CR, number of doses of PD-1 antibody, time off therapy and relapses.

Results

Twenty-four pts were noted to have had a CR and ceased therapy. The median age was 64 (27-83) years. Twenty pts (83%) were BRAF wild type and 4 (17%) pts BRAF mutant. The median number of cycles were 15 on PEM NPP, 18 on NIVO and 11 on r PEM. The median time to CR was 10 months in the PEM NPP/ r PEM groups and 17 months in the NIVO group. The median time off therapy in PEM NPP was 7 months, NIVO was 8 months and r PEM was 2 months. To date only one patient from PEM NPP has relapsed and been successfully re-induced.

Conclusions

This is the first report of a cohort of patients who have intentionally ceased PD-1 based therapy because of CR. While the follow up is short as yet only one patient has relapsed off therapy and has been successfully re-induced. Data such as this is both clinically relevant as we need to be able to discuss cessation for CR with our patients and relevant from a pharmaco-economic perspective given the cost of PD-1 antibodies to society.

Clinical trial identification

No trial protocol number

Legal entity responsible for the study

This has been at the review by the Ethics Committee of Princess Alexandra Hospital

Funding

N/A

Disclosure

V.G. Atkinson: BMS, MSD, Novartis Advisory Board BMS, MSD, Novartis Speaker fees and travel support. All other authors have declared no conflicts of interest.