Nick Mulcahy

June 05, 2017

CHICAGO – "Immune checkpoint inhibitors are likely to change our standard of care in malignant pleural mesothelioma," said Anne Tsao, MD, a medical oncologist from MD Anderson Cancer Center in Houston, Texas, who spoke here at the American Society of Clinical Oncology (ASCO) 2017 Annual Meeting.

Furthermore, antiangiogenic agents, which have a budding role in the treatment of mesothelioma, may eventually be used by clinicians in combination with immunotherapy, she said.

In short, welcome change is coming to this notoriously difficult-to-treat form of lung cancer that currently has only one proven first-line regimen, and none for patients who experience disease relapse or progression.

Dr Tsao served as discussant during a session that featured two new studies, one of immunotherapy in the setting of relapsed disease, and the other of an antiangiogenic agent as part of initial treatment.

In the first study, known as MAPS-2, French researchers concluded that immunotherapy with checkpoint blockade may slow the growth of mesothelioma after relapse. Plus, it appears that immunotherapy may offer something not seen previously in second-line therapy: improved overall survival.

The phase 2 study was conducted in 108 patients who were experiencing relapse after one or two previous lines of therapy, including the pemetrexed/platinum doublet.

The primary endpoint was disease control rate at 12 weeks. That goal was "meaningfully" met, concluded lead study author Arnaud Scherpereel, MD, PhD, a thoracic oncologist at the University Hospital of Lille in France, who spoke at a meeting press conference.

Dr Arnaud Scherpereel

The disease control rate (ie, the rate of patients who experienced response or stable disease) was 44% of patients who received nivolumab (Opdivo, Bristol-Myers Squibb) and 50% of those who received nivolumab plus ipilimumab (Yervoy, Bristol-Myers Squibb).

These results are an improvement upon historical disease control rates of <30% seen with other second- and third-line therapies, he said.

"Immunotherapy makes a big difference with patients in my practice," Dr Scherpereel told Medscape Medical News

"In treating these patients regularly, it really is frustrating to have one option that is of limited duration and benefit," said John Heymach, MD, PhD, a medical oncologist who is also from MD Anderson. He served as a press conference commentator and was referring to pemetrexed-platinum doublet chemotherapy, the only approved first-line treatment.

The new results provide a "clear path" to a new therapeutic option, he added.

Dr Scherpereel also reported that the overall response rate (ORR) was 16.7% with nivolumab (n = 9/54), and 25.9% with nivolumab plus ipilimumab (n = 14/54). These response rates are in keeping with other, smaller studies of checkpoint inhibitors in this setting, such as studies of pembrolizumab, Dr Tsao commented in her discussion.

"This randomized phase 2 trial may be enough to support the use of immune checkpoint inhibitors in this setting," Dr Scherpereel said, "but it is too early to conclude whether nivolumab alone or the combination of nivolumab and ipilimumab is better."

Another expert sounded positive notes about the study.

"This phase 2 study is the largest so far in this setting, and I expect that it will pave the way for more practice-changing research in malignant pleural mesothelioma," said Hongbin Chen, MD, PhD, a medical oncologist at the Roswell Park Cancer Institute in Buffalo, New York, who was not involved in the research.

"The findings showed that both nivolumab monotherapy and combination therapy were active in disease control and prolonging survival," Dr Chen told Medscape Medical News.

More data are needed to determine the utility of combination immunotherapy vs nivolumab alone, said Dr Scherpereel.

He reported that there was more toxicity with the combination: toxicities of all grades and of grade 3 or 4 were slightly increased in the combination arm (86.9% and 18%) in comparison with nivolumab alone (77.8% and 10%). Notably, three treatment-related deaths were observed in the combination arm (one death from metabolic encephalopathy, one from fulminant hepatitis, and one from acute renal failure). But only the death from hepatitis was attributed to the treatment.

Median overall survival among the 63 patients in the nivolumab arm was 10.4 months; it had not yet been reached among the 62 patients in the nivolumab plus ipilimumab arm.

In his presentation, Dr Scherpereel placed these results in historical context, saying median overall survival is usually 6 to 9 months in the second-line setting.

Also, median progression-free survival was 4 months in the nivolumab arm and 5.6 months in nivolumab plus ipilimumab arm.

Dr Tsao described the preliminary survival findings as "highly promising" and "impressive."

He told meeting goers that immunotherapy is also being tested as a first-line therapy for mesothelioma. For example, there is a planned phase 3 trial pitting the combination of nivolumab and ipilimumab vs the current standard of a pemetrexed-platinum doublet.

Another Treatment Approach

In the second study, also phase 2, the antiangiogenic nintedanib (Boehringer Ingelheim), which is approved for use in non–small cell lung cancer, was added to the standard chemotherapy combination of pemetrexed/cisplatin in patients with previously untreated mesothelioma. The addition of nintedanib improved progression-free survival in comparison to placebo: median progression-free survival was 9.4 months with nintedanib vs 5.7 for placebo (hazard ratio, 0.54; P = .01). Median overall survival was also improved, up to 18.3 months vs 14.2 months with placebo, but this difference was not statistically significant.

There is an ongoing phase 3 trial with the same study design that will further inform clinicians about the usefulness of this approach.

The MAPS-2 immunotherapy study was funded by the French Cooperative Thoracic Intergroup. Multiple authors of the nintedanib study have financial ties to industry, including Boehringer Ingelheim, who sponsored the study. Dr Heymach has a financial relationship with Bristol-Myers Squibb, the makers of nivolumab and ipilimumab.

American Society of Clinical Oncology (ASCO) 2017 Annual Meeting. Abstract LBA8507 (immunotherapy) and abstract 8506 (nintedanib). Both presented June 5 2017.

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