OS boost with nivolumab–ipilimumab in malignant pleural mesothelioma
medwireNews: Dual checkpoint inhibition with nivolumab and ipilimumab is associated with prolonged overall survival (OS) relative to chemotherapy in treatment-naïve patients with inoperable malignant pleural mesothelioma, show CheckMate 743 data.
“This is the first positive randomized trial of dual immunotherapy in the first-line treatment of patients with mesothelioma,” said the presenting author at the IASLC’s World Conference on Lung Cancer Virtual Presidential Symposium 2020.
“Therefore [nivolumab plus ipilimumab] should be considered as a new standard of care” for this patient population, added Paul Baas, from the Netherlands Cancer Institute in Amsterdam.
In a prespecified interim analysis of the phase 3 trial, conducted at a median of 29.7 months, median OS was 18.1 months for the 303 participants who were randomly assigned to receive nivolumab 3 mg/kg every 2 weeks alongside ipilimumab 1 mg/kg every 6 weeks for up to 2 years.
This was significantly longer than the median of 14.1 months observed for their 302 counterparts who instead received six cycles of cisplatin or carboplatin plus pemetrexed every 3 weeks, and equated to a hazard ratio (HR) for death of 0.74.
At the 12-month mark, 68% of the immunotherapy group and 58% of the chemotherapy group were alive, while the corresponding 24-month rates were 41% and 27%.
Subgroup analysis showed a significant OS benefit of nivolumab–ipilimumab versus chemotherapy in patients with non-epithelioid (HR=0.46), but not epithelioid, histology, and among those with a PD-L1 expression level of at least 1% (HR=0.69), but not those with lower levels.
But Baas highlighted the descriptive nature of the PD-L1 analysis, thereby “precluding firm conclusions.”
There was no significant difference between groups with respect to progression-free survival, and in fact, the data favored the chemotherapy arm for around the first 8 months, after which the curves crossed, reported the presenter.
The objective response rate was slightly lower in the immunotherapy than chemotherapy group, at 40% versus 43%, but the median duration of response was higher, at 11.0 versus 6.7 months.
Baas noted that “no new safety signals were observed” in the trial. Treatment-related adverse events (TRAEs) of grade 3 or 4 occurred in a comparable 30% of patients given immunotherapy and 32% of those given chemotherapy. But the rate of discontinuation of any component of the regimens due to TRAEs was more than double with immunotherapy, at 15% versus 7%.
There were three treatment-related deaths in the nivolumab plus ipilimumab group, one each due to pneumonitis, encephalitis, and acute heart failure, and one death due to treatment-related myelosuppression in the chemotherapy group.
The discussant agreed that the trial “has shown a transformative improvement” with dual checkpoint inhibition.
He stressed, however, that this benefit appears to be restricted to patients with non-epithelioid histology, primarily due to the “marked chemoresistance” of these patients, who had a median OS of 8.8 months with chemotherapy versus 16.5 months observed for patients with epithelioid histology.
Looking to the future, Dean Fennell, from the University of Leicester in the UK, concluded that “chemoimmunotherapy involving all histologies or selective targeting of non-epithelioid mesothelioma could further extend benefit.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group