Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study

Our plain-English summary of Immune-Checkpoint Inhibitors for Malignant Pleural Mesothelioma: A French, Multicenter, Retrospective Real-World Study, by J.B. Assié, F. Crépin, E. Grolleau, et al (Cancers, 2022).

The study

• Authors: J.B. Assié, F. Crépin, E. Grolleau, A. Canellas, M. Geier, A. Grébert-Manuardi, N. Akkache, A. Renault, P.A. Hauss, M. Sabatini, V. Bonnefoy, A. Cortot, M. Wislez, C. Gauvain, C. Chouaïd, A. Scherpereel, I. Monnet
• Journal: Cancers
• Published: 2022;14(6)
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10−25% objective response rate (ORR) and 40−70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017−July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients’ characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2−5.9) and 12.8 (9.2−16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52−7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22−0.99), progression on the line preceding nivolumab: 2.1 (1.11−3.9) and age > 70 years: 2.5 (1.5−4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08−11.8) and albumin < 25 g/L: 10.28 (1.5−70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.

In plain English

This retrospective study reviewed 109 malignant pleural mesothelioma patients treated at 11 French centers, 2017 to 2021. All had prior platinum-based chemotherapy, then received nivolumab, an immune-checkpoint inhibitor; no asbestos findings were reported. Median age was 69; 82.6% had epithelioid tumors. Tumors responded completely or partially in 17 of 109 (15.6%); disease was controlled in 46.8%. Median progression-free and overall survival were 3.8 months (95% CI 3.2 to 5.9) and 12.8 months (9.2 to 16.4). Multivariable analysis retained only biphasic subtype (8 patients; hazard ratio 3.57, 95% CI 1.08 to 11.8) and albumin below 25 g/L (3 patients; 10.28, 1.5 to 70.7) as significantly linked to shorter overall survival. Age 70 or over was linked to shorter survival in single-factor analysis (hazard ratio 2.5, 1.5 to 4.0), but not significantly after adjustment (1.89, 0.85 to 4.2). Side effects affected 72 of 109 patients, 96% of events grade 1 or 2; three had grade 3. The authors concluded nivolumab is effective in less selected patients, less so over 70, noting the retrospective design, possible selection bias and small subgroups.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective multicenter real-world study of patient records (all patients received nivolumab; no comparison group)
• Who was studied: 109 patients with malignant pleural mesothelioma treated with nivolumab at 11 French centers between 1 September 2017 and 31 July 2021. Median age was 69 years, 67.9% were men, and 82.6% had the epithelioid subtype (10.1% sarcomatoid, 7.3% biphasic). All had received first-line platinum-based chemotherapy.
• Exposure: Nivolumab given as second-line or later treatment, at 3 mg/kg or a flat 240 mg dose every 2 weeks. It was strictly second-line for 51.4% of patients. Asbestos exposure was listed among the baseline parameters, but no asbestos findings are reported.
• Main results:
  • Objective response in 17 of 109 patients (15.6%): 2 complete and 15 partial responses. Stabilized disease in 34 of 109 (31.2%).
  • Disease-control rate of 46.8% for the whole cohort. Progression in 58 of 109 (53.2%).
  • Whole cohort: median progression-free survival 3.8 months (95% CI 3.2 to 5.9) and median overall survival 12.8 months (95% CI 9.2 to 16.4). Median follow-up was 21.13 months.
  • Multivariable analysis of overall survival retained only two factors as significant and independent. Biphasic versus epithelioid subtype: HR 3.57 (95% CI 1.08 to 11.8; p = 0.037). Albumin below 25 g/L versus above 35 g/L: HR 10.28 (95% CI 1.5 to 70.7; p = 0.018). Only 3 patients had albumin below 25 g/L.
  • Age 70 or over (Table 2; the text says over 70) versus under 70 was associated with overall survival in univariable analysis: HR 2.5 (95% CI 1.5 to 4.0; p less than 0.001). In multivariable analysis it was not statistically significant: HR 1.89 (95% CI 0.85 to 4.2; p = 0.118).
  • No factor was retained in multivariable analysis as predictive of an objective response.
  • 72 of 109 patients (66.1%) had an adverse event, 96% of the events grade 2 or lower. Three patients had grade-3 toxicity, and no grade 4 or 5 events occurred.
• The authors' conclusion: The authors concluded that nivolumab is an effective second-line and onward option in less selected patients with malignant pleural mesothelioma, with lower efficacy in patients over 70. They called for prospective trials and ancillary studies to find predictive or prognostic factors.
• Limitations the authors state:
  • Retrospective design, probably with selection bias toward patients who had access to nivolumab during the inclusion period
  • Response was assessed locally, and the timing of evaluations was left to the investigator, which could bias progression-free survival
  • The biphasic subgroup was small (n = 8), which the authors say may have led to a wrong conclusion
  • Few patients had low albumin (denutrition), so prospective studies are needed to validate this finding
  • PD-L1 could not be assessed because it was not routinely measured (analyzed in only 5 patients)

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Pleural Mesothelioma, Prognosis, Clinical Trial, Nivolumab (Opdivo), Epithelioid, Biphasic Mesothelioma.

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