Adding nintedanib to standard of care fails to improve PFS in pleural mesothelioma
Adding nintedanib to standard-of-care pemetrexed-cisplatin doublet chemotherapy does not improve progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM), the phase III LUME-Meso study has shown.
These new findings are in contrast to the study’s phase II results, which showed significant PFS and overall survival (OS) improvements with the addition of nintedanib to standard chemotherapy in this setting.
In the placebo-controlled LUME-Meso study, 458 patients with histologically confirmed epithelioid MPM, no previous systemic therapy, and an Eastern Cooperative Oncology Group performance status of 0–1 were randomized to receive six cycles of pemetrexed-cisplatin doublet chemotherapy plus either nintedanib 200 mg BID or placebo. Patients who did not have disease progression after six cycles of treatment continued to receive maintenance nintedanib or placebo.
“Median PFS by investigator assessment, the primary endpoint of the study, was comparable between the nintedanib group and placebo group [6.8 months vs 7.0 months; hazard ratio (HR), 1.01; 95 percent confidence interval (CI), 0.79 to 1.30; p=0.914]. Similar findings were observed for PFS by independent central review,” reported lead investigator Professor Giorgio Scagliotti of the University of Torino, Italy, who is President of the International Association for the Study of Lung Cancer (IASLC), at the IASLC’s 19th World Conference on Lung Cancer (WCLC 2018) in Toronto, Canada.
In addition, subgroup analysis failed to identify patient groups who might benefit from the addition of nintedanib to doublet chemotherapy.
The secondary endpoint of OS was also similar between the nintedanib group vs placebo group (median, 14.4 months vs 16.1 months; HR, 1.12; 95 percent CI, 0.79 to 1.58; p=0.538).
“Therefore, results of our present study do not support the use of nintedanib in combination with pemetrexed-cisplatin for patients with epithelioid MPM,” said Scagliotti.
Previously, the phase II part of LUME-Meso showed that adding nintedanib to pemetrexed-cisplatin improved PFS and OS in MPM patients, and the effect was particularly evident in those with epithelioid histology. [J Clin Oncol 2017;35:3591-3600] “However, results of our present phase III study did not confirm the phase II findings. The study was discontinued according to the protocol,” highlighted Scagliotti. “The trial reaffirms the need for solid confirmatory studies that are adequately sized to challenge the standard of care in advanced MPM.”
“The side effect profile of nintedanib was consistent with previous nintedanib studies. Patients’ quality of life was not adversely impacted by the addition of nintedanib to chemotherapy,” he added.
“LUME-Meso was well-designed. The two treatment groups were generally well balanced. The outcomes in the placebo group are similar to that observed in previous studies,” commented invited discussant Dr Ross Soo of National University Hospital, Singapore. “Type I error may explain the discordance in PFS between the phase II and phase III findings of LUME-Meso.”