Mesothelioma Immunotherapy Combination Gaining Momentum
Recent studies from France and the Netherlands have shown patients with pleural mesothelioma can benefit significantly from a second-line immunotherapy drug combination.
In separate phase II studies, the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) created a synergy that helped stop or slow tumor growth after traditional chemotherapy had failed.
“Our results add to the growing evidence that immunotherapy is a promising treatment,” wrote lead author Dr. Maria Disselhorst of the Netherlands Cancer Institute in Amsterdam. “The combination of nivolumab plus ipilimumab showed marked efficacy in patients with recurrent malignant pleural mesothelioma.”
Lancet Respiratory Medicine published the study from the Netherlands on January 16, 2019. Lancet Oncology published the study from France on January 18.
Looking Toward First-Line Treatment
Both studies showed similar effectiveness with the combination treatment. The authors referred new mesothelioma patients to the ongoing multicountry phase III study using the nivolumab/ipilimumab combination as a first-line treatment.
There are 17 cancer centers within the United States involved in that clinical trial.
Those include the Moffitt Cancer Center in Tampa; WVU Mary Babb Randolph Cancer Center in Morgantown, West Virginia; Cleveland Clinic Cancer Center in Ohio; Abramson Cancer Center in Philadelphia and Mayo Clinic in Rochester, Minnesota.
Opdivo and Yervoy are both manufactured by pharmaceutical giant Bristol-Myers Squibb.
The two drugs work in similar ways, but target different surface proteins that are found in several cancers.
Opdivo targets the protein PD-L1, and Yervoy targets CTLA-4. Both proteins typically restrict a patient’s immune system and allow the tumor to grow.
Negating those two proteins allows the immune system to better recognize tumors cells. Each of the drugs, known as immune checkpoint inhibitors, had already individually shown effectiveness for mesothelioma treatment. Together, they were better.
The study in France compared the effectiveness of Opdivo alone to the combination of Opdivo and Yervoy. The trial in the Netherlands was a single-arm study of the combination.
“Nivolumab monotherapy, or nivolumab plus ipilimumab combination therapy both showed promising activity in relapsed patients,” wrote the lead author of the French study, Dr. Arnaud Scherpereel from University Hospital of Lille. “Although these results require further confirmation in larger trials, they could now justify the use … by patients who have no other efficient therapeutic options available.”
Results from France
The study in France included 125 patients in 2016, all of whom entered the study after chemotherapy had failed. Results, based on the start of immunotherapy treatment, included:
- 12-Week Disease-Control Rate: 44 percent in Opdivo group and 50 percent in the Opdivo/Yervoy group.
- Average Progression-Free Survival: 4 months and 5.6 months until the cancer worsened, respectively.
- Median Overall Survival: 11.9 months and 15.9 months, respectively.Grade 3 or 4 Toxicities: severe side effects in 14 percent and 26 percent of patients respectively, including three deaths in the combination group.
Results from the Netherlands
The study in the Netherlands included 36 patients from 2016-2017. In the group, 27 were men, and 30 had the epithelioid subtype of mesothelioma. The median time between the last systemic chemotherapy treatment and study enrollment was 6.2 months.
The findings included:
- 12-Week Disease-Control Rate: 68 percent (29 percent with partial response and 39 percent with stable disease).
- 6-Month Disease-Control Rate: 50 percent (38 percent with partial response and 12 percent with stable disease).
- Median Progression-Free Survival: 6.2 months.
- Grade 3 or 4 Toxicities: severe side effects in 34 percent of patients.
“The regimen was well tolerated and toxicity was reversible and considered manageable,” the authors wrote.
Ongoing Clinical Trial
The phase III study of the immunotherapy combination is expected to attract an estimated 600 patients and continue until 2021. The mesothelioma clinical trial is measuring the combination against standard chemotherapy.
There currently is no FDA-approved second-line treatment for mesothelioma. First-line treatment for those are not surgical candidates (the majority of patients) hasn’t changed since 2005.
“Whether our results will translate to a survival benefit needs to be investigated in a phase III trial,” Disselhorst wrote. “More results are awaited.”