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Cancer Therapy AdvisorMARS 2: Chemo Alone May Be Superior to Surgery Plus Chemo in Mesothelioma

Up to 42 months after randomization, patients who received surgery had a greater probability of dying, but there was no discernible difference in overall survival between the two arms after that point.

Recent research from the MARS 2 trial, presented at the 2023 World Conference on Lung Cancer, suggests that mesothelioma patients receiving chemotherapy alone face fewer adverse events and enjoy a better quality of life compared to those undergoing both chemotherapy and surgery.

HCN Medical Memo
For physicians treating mesothelioma, these findings underscore the need for critical reassessment of treatment protocols. Although surgery has long been a cornerstone of mesothelioma treatment, the MARS 2 trial indicates that chemotherapy alone may offer better survival rates and fewer complications. With these compelling data points, it may be time to re-evaluate the utility of surgical interventions, especially as more effective systemic treatments become available for unresectable disease.

Key Points
  • The MARS 2 phase 3 trial enrolled 335 mesothelioma patients and found that those undergoing chemotherapy alone had better overall survival (OS) for the first 42 months from randomization.
  • Hazard ratio for OS favored chemotherapy alone: 1.28; 95% CI, 1.02-1.60; P =.03.
  • Patients in the chemotherapy-alone arm had a significantly lower incidence of grade 3 or higher adverse events (incidence rate ratio 3.6; 95% CI, 2.3-5.5; P <.001).
  • Dr. Eric Lim, the study presenter, stated that abandoning the concept of resectability could open access to more effective treatments for mesothelioma.
  • Discussant Paula Ugalde Figueroa, MD, raised concerns about the study’s methodology, questioning whether outcomes might differ at high-volume surgical centers.

“As a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication…has been associated with a higher risk of death, more serious complications, poorer quality of life, and a higher cost, compared to … chemotherapy alone.”
– Eric Lim, MD, Royal Brompton Hospital and Imperial College London in the UK and Study Presenter

Additional Points
  • No significant difference in OS between the treatment arms was observed beyond 42 months.
  • Baseline characteristics revealed more patients with sarcomatoid mesothelioma and more patients with extension of tumor into the pulmonary parenchyma in the surgery arm.
  • A total of 15 patients (4.5%) did not receive their assigned therapy, but a 10% crossover was accounted for in the study design.

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