Materials and methods

This single-center retrospective study reviewed patient medical records at a tertiary medical college hospital in Udaipur, Rajasthan, India, across a time span of January 2021 to August 2023.

Inclusion and exclusion criteria

This retrospective study reviewed adult patients aged 18 years or older at the time of treatment initiation with a baseline Eastern Cooperative Oncology Group (ECOG) performance status score between 0 and 2 [5]. Eligible individuals had an advanced, metastatic, or inoperable epithelioid malignant pleural mesothelioma histologically diagnosed and confirmed using contrast-enhanced computed tomography (CECT) or fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) scan. Patients were excluded if they presented with alternative histological subtypes, such as sarcomatoid or biphasic variations. Additional exclusion criteria included a prior history of receiving systemic chemotherapy or targeted therapy, as well as a history of active autoimmune conditions requiring systemic immunosuppression.

Objectives

The primary objective of this study was to evaluate the real-world OS, including median OS and one-year OS, and safety profile of first-line nivolumab plus ipilimumab in Indian patients with inoperable epithelioid malignant pleural mesothelioma. Secondary objectives included the assessment of objective response rate (ORR) at first reassessment using modified RECIST criteria and the characterization of the clinical-demographic landscape of this population and toxicity profile.

Methodology

Relevant data of the patients was retrieved from the institute's medical records. All enrolled patients received a standardized weight- and protocol-driven immunotherapy schedule: nivolumab: 240 mg administered via intravenous infusion over 30 minutes, repeated once every two weeks and ipilimumab: 1 mg/kg administered via intravenous infusion over 30 minutes, repeated once every six weeks. Therapeutic cycles proceeded sequentially until documented objective radiological disease progression or the development of unmanageable treatment-limiting toxicity.

Demographic data, physical parameters, pathological and radiological reports were collected and analysed. Baseline FDG PET-CT imaging was done before starting therapy.

Clinical and response assessments

Response evaluation was done after three months of therapy using FDG PET-CT scan and was categorized utilizing the modified Response Evaluation Criteria in Solid Tumors in malignant pleural mesothelioma (mRECIST) [6]. On the basis of first reassessment at three months, further therapy was continued. Those patients who showed either stable disease (SD), partial response (PR) or complete response (CR) were continued on same treatment and were followed up until death. Survival analysis was done after 12 months of follow-up.

Safety profiles and treatment-related adverse events (TRAEs) were closely recorded at every treatment interval. Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v5.0) [7].

Statistical analysis

For statistical analysis, data were entered into a Microsoft Excel (Redmond, WA, USA) spreadsheet. Data has been summarized as median, mean and standard deviation for numerical variables and count and percentages for categorical variables.

Time-to-event data were analyzed using the Kaplan-Meier method to estimate the cumulative survival probability of the cohort over time [8]. The survival time was calculated from the date of diagnosis to the date of progression or death. Median survival time along with its 95% confidence interval (CI) was calculated to summarize the cohort's trajectory. All statistical analyses and survival curves were generated using SPSS Statistics for Windows, Version 25 (IBM Corp., Armonk, NY, USA).