OBJECTIVES : For PD(L)-1 inhibitors such as pembrolizumab, OS is a key driver of clinical- and cost-effectiveness. Submissions to the reimbursement authorities often require the extrapolation of observed OS data from the pivotal clinical trials to project patients’ survival beyond the trial period. The aims of this study are: to analyse the accuracy of extrapolations accepted by the PBAC for pembrolizumab submissions for advanced melanoma and metastatic NSCLC PD-L1 TPS>=50% compared with what was subsequently observed in long-term trial follow-up; and to understand whether the time horizon accepted by the PBAC adequately captures the treatment benefit of pembrolizumab.

METHODS : To focus on treatments with a high disease burden and budget impact, the study was limited to indications with a treated population of greater than 500 patients per year. A search was conducted for pembrolizumab public summary documents (PSDs) as well as published long-term OS data with at least 2 years follow-up. Extrapolations and recommended time horizons reported in the relevant PSDs were extracted to compare the accuracy of OS projections versus the most mature data available.

RESULTS : The review identified two comparisons of OS extrapolations: the KN-006 trial in patients with advanced melanoma (median follow-up duration 57.7 months; maximum 62.1 months) and KN-024 trial in patients with metastatic NSCLC PD-L1 TPS>50% (median follow-up duration 44.4 months, maximum 52.9 months). The extrapolations accepted by the PBAC in recommending pembrolizumab for advanced melanoma estimated an overall survival rate of 24.0% at 49 months and 33.2% at 40.5 months for metastatic NSCLC PD-L1 TPS>=50%. This underestimated OS of pembrolizumab monotherapy by absolute percentages of 18.2% and 9.1%, respectively compared to the most mature OS trial data available.

CONCLUSIONS : The results demonstrate that the extrapolation accepted by PBAC underestimated OS compared to longer-term data for pembrolizumab monotherapy in advanced melanoma and metastatic NSCLC PD-L1 TPS>=50%.