Second-Line Anetumab Ravtansine Yields Manageable Safety Profile, Not Superior to Vinorelbine in Relapsed MPM

Although a managable safety profile was observed with anetumab ravtansine in the second long, the treatment did not appear superior to vinorelbine (Navelbine) in patients with relapsed mesothelin-positive malignant pleural mesothelioma, according to a findings from a randomized phase 2 trial (NCT02610140) published in The Lancet Oncology.

The median follow-up for anetimab ravtansine was 4.0 months vs 3.9 months with vinorelbine, with a median progression-free survival (PFS) of 4.3 months (95% CI, 4.1-5.2) vs 4.5 months (95% CI, 4.1-5.8) in both groups, respectively (HR, 1.22; 95% CI, 0.85-1.74; log-rank P = .86).

A total of 547 patients provided samples for the mesothelin expression analysis, of which 425 were positive and included in the study. After screening, 248 patients were enrolled and included in the intent-to-treat population, 166 of whom were randomized to receive anetumab ravtansine and 82 were in the vinorelbine arm.

Patients received 6.5 mg/kg as a maximum tolerated dose of anetumab ravtansine through intravenous infusion once every 3 weeks for 1 hours on day 1 of each 21-day cycle or 2.2 mg/kg once every week. Patients received 30 mg/m2 once every week of vinorelbine through an intravenous injection for 6 to 10 minutes.

At the data cutoff, 105 patients in the anetumab ravtansine group compared with 43 in the vinorelbine group had progressed or died. The subgroup analysis did not show any significant difference in PFS between treatment arms, and patient-reported outcomes further highlighted that anetumab ravtansine was not superior to vinorelbine.

During longer follow-up, 113 vs 48 patients in each group had died with a median follow-up of 8.6 months and 8.7 months (95% CI, 3.5-14.3) in the anetumab ravtansine and vinorelbine groups, respectively. The median overall survival (OS) in the anetumab ravtansine group was 9.5 months (95% CI, 8.3-12.3) and was 11.6 months (95% CI, 8.6-13.1; HR, 1.07; 95% CI, 0.76-1.51; log-rank P = .66) in the vinorelbine group.

The exploratory analysis which was performed at the study’s completion found that 127 patients in the anetumab ravtansine group had died compared with 59 in the vinorelbine group. The median OS remained largely unchanged at the study cutoff (HR, 0.98; 95% CI, 0.72-1.34).

In the anetumab ravtansine group, the median duration of response was 7.4 months (95% CI, 6.0–not estimable) vs 6.7 months (95% CI, 3.0-10.3) in the vinorelbine group, and the durable response rate was 7.2% (95% CI, 3.8%-12.3%) vs 4.9% (95% CI, 1.3%-12.0%), respectively.

The safety analysis included 163 patients treated with anetumab ravtansine and 72 treated with vinorelbine. Seventy-eight patients in the anetumab ravtansine group had grade 3 or 4 treatment-emergent adverse effects (TEAEs) compared with 53 with the vinorelbine group. The most common TEAEs in both groups included neutropenia, pneumonia, and neutrophil count decrease.

In 10 patients in the anetumab ravtansine group had treatment-emergent deaths related to pneumonia (n = 3), sepsis (n = 2), dyspnea (n = 2), atrial fibrillation (n = 1), general physical health deterioration (n = 1), hepatic failure (n = 1), mesothelioma (n = 1), and renal

failure (n = 1). One patient in the vinorelbine arm died due to pneumonia.

Serious drug-related TEAEs that were seen in 12 patients in the anetumab ravtansine group and 11 in the vinorelbine group, the most common of which were infusion-related reactions were neutropenia and pneumonia.

TEAEs that led to dose modifications occurred in 75 patients in the anetumab ravtansine group and 58 in the vinorelbine group. Due to TEAEs, discontinuation was necessary in 45 patients in the anetumab ravtansine group and 13 in the vinorelbine group.

Reference

Kindler HL, Novello S, Bearz A, et al. Anetumab ravtansine versus vinorelbine in patients with relapsed, mesothelin-positive malignant pleural mesothelioma (ARCS-M): a randomised, open-label phase 2 trial. Lancet Oncol. 2022;23(4):540-552. doi:10.1016/S1470-2045(22)00061-4