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WCLC: Bevacizumab Plus Standard Chemotherapy Improves Survival in Mesothelioma

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Key Points

  • In unresectable malignant pleural mesothelioma, the addition of bevacizumab 15 mg/kg to pemetrexed/cisplatin significantly improved overall survival and progression-free survival.
  • Median overall survival was 18.8 vs 16.1 months (hazard ratio = 0.76; P = .0126). 
  • Median progression-free survival was 9.6 vs 7.5 months (hazard ratio = 0.61; P < .0001).

The standard of care for malignant pleural mesothelioma may be poised for change, judging by results from a study (Abstract ORAL11.01) by the French Cooperative Thoracic Intergroup.

The addition of bevacizumab (Avastin) in the first-line setting to the current standard of care, pemetrexed (Alimta)/cisplatin, improved overall survival by almost 3 months in the phase III MAPS trial. These results were presented at the 16th World Conference on Lung Cancer. The findings were reported by Arnaud Scherpereel, MD, Head of the Pulmonary and Thoracic Oncology Department and Professor at the University Hospital in Lille, France.

“Adding bevacizumab to pemetrexed/cisplatin doublet significantly increased both progression-free survival (by 2 months) and overall survival (by 2.75 months), with only a slight, manageable increase of toxicity,” Dr. Scherpereel said.

Dr. Scherpereel noted that mesothelioma is a very aggressive tumor with no validated curative treatment. Maximum overall survival hovers around 13 months, and “no improvement has been achieved in this disease in more than a decade,” he said.

According to Dr. Scherpereel, the scenario has changed with the results of MAPS, which could herald “a new treatment paradigm” for patients with mesothelioma who are eligible for bevacizumab and are not candidates for potentially curative surgery.

Efficacy and Safety

MAPS is a phase II/III open-label, 73-center study conducted between 2008 and 2014. It enrolled 448 patients with mesothelioma not amenable to curative treatment, randomly assigning them to standard chemotherapy with pemetrexed/cisplatin or to the same regimen plus bevacizumab (15 mg/kg). After six cycles, patients on the experimental arm continued to receive bevacizumab alone until disease progression.

After a median follow-up of 39.4 months, the primary endpoint, median overall survival, was significantly higher in patients on the experimental arm receiving triplet therapy (18.8 vs 16.1 months; hazard ratio = 0.76; P = .0126). Median progression-free survival was also significantly longer with the triplet (9.6 vs 7.5 months; hazard ratio = 0.61; P < .0001). The median overall survival of the control arm was longer than has been observed in historical series or previous trials, perhaps because study subjects were unusually fit, Dr. Scherpereel suggested.  

Grade 3 to 4 toxicities were observed in 71% of the bevacizumab arm and 62% of the control arm. Hematologic toxicities were not increased with bevacizumab, but nonhematologic adverse events were greater with triplet therapy, including a higher incidence of creatinine elevations (39% vs 28%), hypertension (56% vs 1%), arterial and venous thromboembolic events (7% vs 1%), and low-grade hemorrhage (41% vs 7%).

There was no significant difference between the arms in terms of percent of drug delivered or proportion of patients receiving second-line treatment—therefore, these factors do not explain bevacizumab’s benefits, Dr. Scherpeerel said.

'Landmark Study'

James Jett, MD, of National Jewish Health in Denver, Colorado, moderated the press briefing where the results were presented.  He called MAPS a “landmark study” that could change the standard of care in this malignancy. Martin J. Edelman, MD, Professor of Medicine at the University of Maryland, Baltimore, agreed in his discussion of the study at the Highlights of the Day session at the meeting.

Dr. Edelman noted that mesothelioma is a highly aggressive and lethal disease that is occasionally resectable and responds only modestly to chemotherapy. The MAPS findings suggest that the triplet of pemetrexed/cisplatin/bevacizumab will become a new standard of care, he said.

“How this will be integrated with novel therapies that are coming remains to be seen,” he added, “but nevertheless, it’s nice to see a positive study in mesothelioma. It’s not something we are used to seeing.” 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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