Phase III study shows nintedanib combo therapies did not improve PFS or OS in malignant pleural mesothelioma

27 Sep 2018

Findings from a recent study demonstrate that triple angiokinase inhibitor nintedanib combined with standard-of-care pemetrexed/cisplatin does not impact progression-free survival (PFS) and overall survival (OS) for unresectable malignant pleural mesothelioma (MPM) patients with epithelioid histology.

Giorgio V. Scagliotti, M.D., Ph.D., of the University of Turin’s Department of Oncology and S. Luigi Hospital, and president of the International Association for the Study of Lung Cancer (IASLC), presented these findings at the IASLC’s 19th World Conference on Lung Cancer (WCLC) in Toronto, Canada.

MPM is a rare but aggressive disease and if left untreated, median survival is six to nine months.

Standard first-line treatment of pemetrexed/cisplatin typically yields a median OS of approximately one year for patients with unresectable MPM.

When Phase II data of LUME-Meso showed patients with epithelioid histology derived the greatest benefit from nintedanib added to pemetrexed/cisplatin in terms of improved PFS versus placebo and a trend towards improved OS, the Phase III protocol of LUME-Meso was amended to focus solely on this subgroup.

Phase III of the global, randomized, double-blind, placebo-controlled study evaluated 458 patients with confirmed MPM of epithelioid subtype with no previous systemic chemotherapy and an Eastern Cooperative Oncology Group performance status (ECOG PS) between zero and one.

Patients were randomized 1:1 to receive combination treatment with up to six cycles of pemetrexed (500 mg/m2)/cisplatin (75 mg/m2) on Day 1, plus nintedanib (200 mg bid) or matched placebo on Day 2 through Day 21.

After completing the combination treatment phase, patients with no disease progression received continued maintenance therapy with nintedanib or placebo.
The results of the study did not show any statistically significant and clinically meaningful improvements in the primary endpoint—PFS—or key secondary points.

These results, which differed from the previously published Phase II data, do not support the use of nintedanib in combination with pemetrexed/cisplatin for patients with MPM of epithelioid subtype.

“Unfortunately, the Phase III results of LUME-Meso did not confirm that nintedanib in combination with pemetrexed/cisplatin prolongs patients’ lives,” said Dr. Scagliotti. “However, the trial reaffirms the need for solid confirmatory studies that are adequately sized, to challenge the standard of care in advanced malignant mesothelioma.”

Source: IASLC