Bevacizumab Plus Pemetrexed and Cisplatin ‘Standard of Care’ for Pleural Mesothelioma

Bevacizumab increases overall survival when added to cisplatin and pemetrexed for the treatment of pleural mesothelioma

medwireNews: The addition of the vascular endothelial growth factor A inhibitor bevacizumab to chemotherapy significantly extends overall survival (OS) for patients with newly diagnosed, unresectable malignant pleural mesothelioma, suggest phase III trial results.

OS was a median of 18.8 months for the 223 patients aged 18–75 years who were randomly assigned to receive up to six cycles of open-label bevacizumab 15 mg/kg in 21-day cycles alongside cisplatin and pemetrexed compared with 16.1 months for the 225 patients who were given the chemotherapy alone, giving a significant hazard ratio (HR) of 0.77.

“[T]he 2.7 month OS improvement could be viewed as slight, but it still accounts for the longest OS ever obtained in a large controlled trial of pleural mesothelioma”, say Gérard Zalcman, from the University of Caen in France, and co-investigators in The Lancet.

They emphasize: “This result has important implications for future first-line treatment of the disease because the pemetrexed plus cisplatin plus bevacizumab regimen should be considered as a new treatment option for patients who are eligible to receive bevacizumab and are not candidates for curative-intent surgery.”

Writing in an accompanying comment, Marjorie Zauderer, from Memorial Sloan Kettering Cancer Center in New York, USA, notes that the OS benefit occurred despite bevacizumab-treated patients being more likely to stop treatment because of toxicity than those given chemotherapy alone (24.3 vs 6.0%).

Indeed, grade 3 or 4 adverse events were significantly more common with bevacizumab, affecting 71% of 222 assessed patients versus 62% of 224, with the greatest differences including increased cardiovascular side effects, hypertension, haemorrhage and creatinine elevation among bevacizumab-treated patients.

“In patients without contraindications to bevacizumab, addition of bevacizumab to cisplatin and pemetrexed is appropriate, with acknowledgment that toxic effects and treatment discontinuation will be more common with than without bevacizumab”, she writes.

Despite the “impressive results”, questions remain over the role of bevacizumab for pleural mesothelioma subgroups, such as patients aged over 75 years and those who are unable to tolerate cisplatin, the commentator observes.

Marjorie Zauderer suggests, however, that future studies should focus on promising new drugs used alone or alongside other novel agents rather than in combination with existing treatments that are likely to bring only modest benefits.

“While such work continues, those patients with pleural mesothelioma who are not candidates for clinical trials or who do not have access to such opportunities, but who do not have contraindications to bevacizumab, should be offered [the] three-drug treatment as a new standard of care”, she concludes.

References

Zalcman G, Mazieres J, Margery J, et al. Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 2015; Advance online publication 21 December. DOI: dx.doi.org/10.1016/S0140-6736(15)01238-6

Zauderer MG. A new standard for malignant pleural mesothelioma. Lancet 2015; Advance online publication 21 December. DOI: dx.doi.org/10.1016/S0140-6736(15)01311-2

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