Reuters Health – 05/02/2021 – Gemcitabine maintenance therapy after first-line chemotherapy significantly prolonged progression-free survival (PFS) in patients with malignant mesothelioma, according to results of the Dutch NVALT19 trial.
“Almost all patients with malignant mesothelioma eventually have disease progression after first-line therapy. Previous studies have investigated maintenance therapy, but none has shown a great effect,” Dr. Cornedine J. de Gooijer of the Netherlands Cancer Institute, in Amsterdam, and colleagues point out in The Lancet Respiratory Medicine.
NVALT19 was a randomized, open-label, phase-2 trial conducted in 18 hospitals in the Netherlands. The trial enrolled 130 adults with unresectable malignant mesothelioma with no evidence of disease progression after at least four cycles of first-line chemotherapy with platinum and pemetrexed, WHO performance status of 0 to 2, adequate organ function and measurable or evaluable disease.
Half were randomly allocated to maintenance intravenous gemcitabine (1,250 mg/m2 on days 1 and 8, in cycles of 21 days) plus supportive care and half to best supportive care alone. Treatment continued until disease progression, unacceptable toxicity, serious intercurrent illness, patient request to stop therapy, or need for any other anticancer agent, except for palliative radiotherapy.
The patients were followed for a median of 36.5 months. No patient was lost to follow-up. The results showed significantly longer PFS in the gemcitabine group (median 6.2 months vs. 3.2 months; hazard ratio: 0.48; 95% confidence interval, 0.33 to 0.71).
At data cutoff, more than three-quarters of the patients had died, with a median overall survival of 16.4 months in the gemcitabine group versus 13.4 months for supportive care alone (HR, 0.90; 95% CI, 0.60 to 1.34).
Grade 3-4 adverse events in more than half of patients taking gemcitabine (52%) compared with 16% of those not taking gemcitabine. The most common adverse events were anemia, neutropenia, fatigue or asthenia, pain, and infection in the gemcitabine group, and pain, infection, and cough or dyspnea in the supportive-care group. One patient (2%) in the gemcitabine group died, due to a treatment-related infection.
This study, write the researchers, confirms the activity of gemcitabine after first-line chemotherapy in patients with unresectable malignant mesothelioma, “an aggressive malignancy with few therapeutic options. Although a benefit in terms of overall survival was not seen, our finding of improved progression-free survival has important consequences for the treatment of patients with malignant mesothelioma.”
In a linked comment, Dr. Anna Nowak of the National Center for Asbestos Related Diseases, University of Western Australia, in Perth, says the “strongly positive” result for PFS with gemcitabine in the phase 2 NVALT19 trial “compares favorably to maintenance bevacizumab in mesothelioma.”
“If this trial had been completed a decade ago, it might have triggered a randomized phase 3 trial. However, in 2021, our next challenge is to understand where this option of gemcitabine will fit in with the changing landscape of malignant mesothelioma treatment,” Dr. Nowak writes.
Last October, the U.S. Food and Drug Administration (FDA) approved the first new treatment for mesothelioma in 16 years, as ipilimumab and nivolumab in combination led to a survival advantage over combination chemotherapy with platinum and pemetrexed.
“The NVALT19 trial provides us with an option of switch-maintenance gemcitabine without sufficient evidence for FDA approval, at a time when our first-line management for this disease is changing. Chemotherapy will still be an option in mesothelioma treatment, but it might move into the second line of therapy for some patients,” writes Dr. Nowak.
She says she has “no doubt that some clinicians will consider adding gemcitabine, a safe and relatively low-cost drug, to their patient management, particularly when progression would have major consequences for symptom burden.”
“This new information from the NVALT19 trial could provide an opportunity for the mesothelioma community to consider novel clinical trial designs that can rapidly and inexpensively evaluate readily available treatments, such as registry clinical trials,” Dr. Nowak concludes.
The study had no commercial funding. Two authors have disclosed relationships with Eli Lilly, which markets gemcitabine as Gemzar.
SOURCE: https://bit.ly/3cF7aXk and https://bit.ly/36Kwcki Lancet Respiratory Medicine, online January 27, 2021.
By Reuters Staff
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