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Chemotherapy alone may produce better outcomes than surgery plus chemotherapy in patients with mesothelioma, according to research presented at the 2023 World Conference on Lung Cancer.
In this phase 3 trial, MARS 2, patients who received chemotherapy and underwent extended pleurectomy decortication had more serious adverse events and worse quality of life than patients who received chemotherapy alone.
Patients who underwent surgery also had a higher risk of death up to 42 months from randomization. There was no significant between-arm difference in overall survival (OS) beyond 42 months, though patient numbers were small at that time point.
This trial (ClinicalTrials.gov Identifier: NCT02040272) enrolled 335 patients with tissue-confirmed, resectable mesothelioma. All patients received 2 cycles of chemotherapy with a platinum agent and pemetrexed. After a CT scan to assess resectability, patients were randomly assigned to receive up to 4 cycles of the same chemotherapy alone (n=166) or after surgery (n=169).
Baseline characteristics were generally well balanced between the treatment arms. Exceptions included more patients with sarcomatoid mesothelioma in the surgery arm (4.7% vs 1.8%), more patients with extension of tumor tissue into underlying pulmonary parenchyma in the surgery arm (83.3% vs 50.0%), and fewer patients with diaphragmatic muscle involvement in the surgery arm (25.0% vs 58.3%).
A total of 15 patients (4.5%) did not receive their assigned therapy. However, the researchers accounted for 10% crossover in their study design, according to study presenter Eric Lim, MD, of Royal Brompton Hospital and Imperial College London in the UK.
Results
OS favored chemotherapy alone for the first 42 months from randomization (hazard ratio [HR], 1.28; 95% CI, 1.02-1.60; P =.03). After 42 months, the difference in OS disappeared (HR, 0.48; 95% CI, 0.18-1.29; P =.15), but Dr Lim noted that there were only 15 patients in each arm at that time.
Dr Lim also noted that a higher risk of death in the surgery arm was seen when the researchers adjusted for crossover, number of chemotherapy cycles, and additional treatment.
“[S]topping surgery would increase survival by 28%,” Dr Lim said. “If we were to take things one step further and actually relinquish the entire concept of resectability in mesothelioma, we would be able to open access to effective systemic treatments currently licensed for unresectable disease.”
Progression-free survival was not significantly different between the treatment arms (HR, 0.90; 95% CI, 0.72-1.11; P =.33).
The risk of grade 3 or higher adverse events was greater for patients in the surgery arm than for those in the chemotherapy-alone arm (incidence rate ratio 3.6; 95% CI, 2.3-5.5; P <.001). Patients in the surgery arm had a greater risk of repeat interventions; cardiac disorders; infections or infestations; and respiratory, thoracic, or mediastinal disorders.
Dr Lim noted that global quality of life was inferior with surgery as well. “For every single statistically significant outcome, it was worse for surgery,” he said.
Implications
“As a surgeon standing here, you have no idea how much it pains me to conclude that extended pleurectomy decortication — an operation that we have been offering for over 70 years — has been associated with a higher risk of death, more serious complications, poorer quality of life, and a higher cost, compared to … chemotherapy alone,” Dr Lim said.
In a follow-up presentation, discussant Paula Ugalde Figueroa, MD, of Brigham and Women’s Hospital in Boston, raised questions and concerns about these results. Firstly, she pointed out that, beyond 42 months, there was no significant difference in OS between the treatment arms.
She also noted that there were key differences between the treatment arms at randomization. “There’s a significant difference when we look at the rate of diaphragmatic infiltration between the groups or lung infiltration between the groups,” she said.
She added that nearly half (45%) of patients enrolled in MARS 2 were treated at centers with low surgical volumes. “Would the outcome be different in exclusively high-volume centers?” she asked.
Dr Lim countered that, with 1 exception, the centers included in this study are national centers of surgical expertise for mesothelioma.
Disclosures: No disclosures were provided.
Reference
Lim E, Waller D, Lau K, et al. MARS 2: A multicentre randomised trial comparing (extended) pleurectomy decortication versus no radical surgery for mesothelioma. Presented at WCLC 2023. September 9-12, 2023. Abstract PL03.10.
This article originally appeared on Cancer Therapy Advisor
