Patient-reported outcomes outcomes from the Check-Mate 743 trial demonstrated improved symptom burden and maintained overall health status with the use of nivolumab/ipilimumab over chemotherapy, in patients with unresectable malignant pleural mesothelioma.
Patient-reported outcomes outcomes (PROs) from the Check-Mate 743 trial (NCT02899299) demonstrated improved symptom burden and maintained overall health status with the use of nivolumab/ipilimumab (Opdivo-Yervoy) over chemotherapy, in patients with unresectable malignant pleural mesothelioma (MPM).1
“These [PRO] results are certainly supporting the outcome of Check- Mate 743 for the use of [nivolumab/ipilimumab] as a first-line treatment for patients with unresectable mesothelioma where there is a clear need for the improvement in survival for these patients,” Alessandra Fontecedro, MD, of the University of Zurich, Switzerland, explained. Her remarks followed a presentation of the PRO results during the European Society for Medical Oncology Immuno-Oncology Virtual Congress 2020.
Nivolumab-ipilimumab is an immunotherapy doublet approved for patients with treatment-naive unresectable MPM.
CheckMate 743 enrolled 605 patients with unresectable MPM and randomized them 1:1 to nivolumab 3 mg/kg every 2 weeks plus 1 mg/kg ipilimumab every 6 weeks for up to 2 years, or to 6 cycles of chemotherapy given every 3 weeks. In the chemotherapy arm, patients received 6 cycles of cisplatin 75 mg/m2 or carboplatin area under the curve (AUC) 5 plus pemetrexed 500 mg/m2 every 3 weeks.
The primary end point of the study was overall survival (OS) and secondary end points were objective response rate, disease control rate, and progression-free survival.
Investigators also looked at disease-related symptom burden, using the Lung Cancer Symptom Scale for mesothelioma (LCSS-Meso) average symptom burden index (ASBI) and 3-item global index (3-IGI). Additionally, they evaluated overall health status using the EQ-5D-3L visual analog scale (VAS) and utility index (UI) in all study patients.
The study authors observed treatment-related adverse events (TRAEs) of any grade in 80% of patients treated with the immunotherapy combination compared with 82% of those who received chemotherapy. Events occurring in 15% or more of patients included diarrhea and pruritis in the immunotherapy arm compared with nausea, anemia, neutropenia, fatigue, decreased appetite, and asthenia in the chemotherapy arm.
Serious TRAEs in the nivolumab-ipilimumab arm included 21 any-grade events and 15 grade 3/4 events compared with 8 and 6, respectively, in the chemotherapy arm.
“This study will soon change the way we treat patients in the first-line setting,” Fontecedro said.
By the PRO measurements, the LCSS-Meso ASBI showed a reduction in symptom burden from baseline that favored nivolumab and ipilimumab for each of the 6 symptoms except cough. The reduction in fatigue with the combination was most substantial, with a mean change of –9.6. The mean change in overall ASBI from baseline was –3.8, although this did not reach clinically important difference thresholds (minimal important difference [MID], Å} 10 score change).1
In terms of the LCSS-Meso 3-IGI, which looked at symptom distress, health-related quality of life (QOL), and interference with activity level, the symptom burden and impact on QOL was lessened with the nivolumab and ipilimumab. The total 3-IGI score improved 16.6 points with nivolumab-ipilimumab, although this did not reach the MID threshold of 30 points.
General health status, measured by EQ-EQ-5D-3L VAS, improved over time in patients treated with nivolumab-ipilimumab.
The time to deterioration of symptom burden based on LCSS-Meso ASBI showed a hazard ratio of 0.52 (95% CI, 0.36-0.74) favoring the combination arm, although the drop-off in assessments in the chemotherapy arm after 6 months made this harder to interpret.
Fontecedro discussed the impact of the PROs from the trial. She explained that reviewing and understanding the PRO data helps tailor patient therapy and ultimately improve outcomes, patient-physician communication, and quality and performance. As such, she suggested that PRO measurement tools have the potential to improve the management of MPM.
Scherpereel A, Antonia S, Bautista Y, et al. First-line nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) for the treatment of unresectable malignant pleural mesothelioma (MPM): patient-reported outcomes (PROs) from CheckMate 743. Ann Oncol. 2020;31(suppl 7):S1441-S1451. doi:10.1016/j.annonc.2020.10.603