medwireNews: Adding ramucirumab to gemcitabine may significantly improve survival outcomes for patients with malignant pleural mesothelioma who have progressed on first-line platinum–pemetrexed regimens, suggest findings from the phase 2 RAMES study presented at the virtual 2020 ASCO Annual Meeting.
Maria Pagano (AUSL-IRCCS Reggio Emilia, Italy) reported a median overall survival (OS) of 13.8 months among the 80 patients who were randomly assigned to receive ramucirumab 10 mg/kg on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8 of each 21-day cycle. This was significantly longer than the median OS of 7.5 months observed among the 81 patients who received placebo plus gemcitabine, and gave a hazard ratio for death of 0.71.
The 6- and 12-month OS rates in the ramucirumab–gemcitabine group were 74.7% and 56.5%, respectively, compared with 63.9% and 33.9% in the placebo–gemcitabine group.
The OS benefit afforded by the ramucirumab and gemcitabine combination was independent of patient age (≤70 vs >70 years), tumor stage (locally advanced vs metastatic), histotype (epithelioid vs non-epithelioid), and the duration of progression-free survival with first-line chemotherapy (≤6 vs >6 months), noted Pagano.
The addition of ramucirumab to gemcitabine was also associated with better median progression-free survival (PFS), at 6.2 months compared with 3.3 months for placebo plus gemcitabine.
There were no complete responses in either treatment arm and the rate of partial responses was lower in the ramucirumab than placebo group, at 6.25% versus 9.88%, but a higher proportion of patients achieved stable disease with ramucirumab, giving disease control rates of 72.50% and 51.86%, respectively.
In all, seven patients in the ramucirumab–gemcitabine arm discontinued treatment due to adverse events (AEs), as did four of the patients in the gemcitabine–placebo arm.
The most common grade 3 or higher AEs associated with ramucirumab plus gemcitabine were fatigue (5.00%), neutropenia (3.75%), thrombocytopenia (2.50%), aspartate aminotransferase or alanine aminotransferase increases (2.50%), and nausea and vomiting (1.25%).
But Pagano said that “[t]he addition of ramucirumab to gemcitabine did not result in an increase of toxicity,” and added that the “safety profile was [as] expected for anti-angiogenesis agents, in particular for hypertension and thrombosis,” both of which occurred at a higher rate in the ramucirumab group, at approximate rates of 14.0% and 9.2%, respectively, versus 1.0% and 1.9%.
Therefore, Pagano concluded: “Ramucirumab plus gemcitabine combination can represent a new option in the second-line treatment of [malignant pleural mesothelioma] patients.”
And she added that “[quality of life] evaluation and correlation with mutational genomic profiles are in progress.”
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