Nivolumab for pre-treated malignant pleural mesothelioma patients: real world evidence

To date, the potential of PD-1 blockade in the treatment of malignant pleural mesothelioma (MPM) remains to be ill-defined. Real-world data from the Netherlands, presented at WCLC 2020, suggest that a (small) percentage of pre-treated MPM patients might derive a clinical benefit from nivolumab. Higher levels of albumin and the expression of PD-L1 were identified as potential biomarkers, but this remains to be validated in a larger dataset.

Introduction

Malignant pleural mesothelioma (MPM) is an uncommon cancer with a low survival rate. In several phase II studies, the PD-1 inhibitors nivolumab and pambrolizumab yielded promising results in the second-line treatment of MPM, but the subsequent phase III PROMISE-meso trial failed to confirm this. During WCLC 2020, results of a real-world study were presented shedding some more light on the potential role of anti-PD1 therapy in this setting. In total, 107 MPM patients, who had progressed on first line therapy and who did not receive maintenance immunotherapy or systemic steroids were included in this analysis. Al these patients received nivolumab at a dose of 3 mg/kg in 2 centres in the Netherlands, irrespective of PD-L1 expression. 

Higher response rate among PD-L1 positive patients

At a median follow-up of 14.1 months, the median progression-free (PFS) and overall survival (OS) were reported at 2.3 and 6.7 months, respectively. When looking into the data in function of the MPM histology, the investigators noticed a numerically longer median OS for patients with an epithelioid histology compared to patients with a non-epithelioid tumour (median OS: 7.4 vs. 4.8 months; p= 0.082). No difference in PFS was observed. Assessed by PD-L1 expression status, PD-L1 positive (≥1%) MPM patients obtained a significantly better objective response rate (ORR), compared to PD-L1 negative (<1%) patients (ORR: 36% vs. 9%; OR[95%CI]: 1.31[1.00-1.72], p= 0.05). This difference translated into a clinically relevant, but not statistically significant PFS benefit (median PFS: 4.2 vs. 1.7 months, p= 0.11). Not surprisingly, patients with a partial response (PR) had a better PFS probability compared to patients who only achieved disease stabilization (p= 0.0075). Also the median OS was better in PR patients compared to patients with stabilised disease or with disease progression (median OS: not reached, 10.2 and 6.4 months, respectively; p< 0.0001). At time of analysis, none of the PR-patients had died, while 2 had progressed. Albumin was the only peripheral blood parameter that showed an association with treatment outcome in this study. When assessed by albumin quartiles (<38 mg/dL, 38-40 mg/dL, 41-43 mg/dL, >43 mg/dL), an albumin >38 mg/dL seemed to be associated with a better OS compared to an albumin evel of <38 mg/dL (median OS: 8.0 vs. 2.5 months; 6-month OS rate: 74% vs. 34%, p= 0.00047).

Conclusion

The ORR and median OS results obtained with nivolumab in this real-world cohort re lower than what was observed in previously reported phase II and III trials. Nevertheless, some patients did seem to have a clinical benefit from nivolumab. With respect to predictive biomarkers, a lack of PD-L1 expression and a low albumin level at baseline were found to be negatively associated with survival. If validated, these factors may be useful selection criteria to identify MPM patients who may receive clinical benefit from nivolumab monotherapy in a second line setting.

Reference

Belderbos R et al., Nivolumab in pre-treated malignant pleural mesothelioma. Presented at WCLC 2020. Abstract OA09.06.