It’s my pleasure and honour to present to you on behalf of my colleagues and friends from the French Cooperative Thoracic Intergroup the results of our randomised phase II trial, MAPS-2, assessing second or third line nivolumab versus nivolumab plus ipilimumab in malignant pleural mesothelioma patients.
Malignant pleural mesothelioma is an aggressive and quite rare cancer even if because of its links with asbestos we could expect an increase of incidence due to the wide use of asbestos still in many countries. There is no validated curative treatment so far. Moreover there is no treatment for patients beyond first line chemotherapy based on pemetrexed and this is responsible for the poor outcome of these patients with a disease control rate usually below 30% and a median overall survival maximum of 6-9 months usually with all the treatment we have so far as second or third line treatment.
Anti-tumour immunotherapy by immune checkpoints such as anti-PD-1 combined or not with anti-CTLA-4 may improve the prognosis of these patients as suggested by the results we had already in melanoma patients and in lung cancer patients. Also based on some preliminary data obtained with anti-PD-1, pembrolizumab, in mesothelioma.
In this randomised non-comparative phase II trial we recruited patients with validated histological diagnosis of malignant pleural mesothelioma with unresectable cancer with documented progression after a maximum of one or two lines of chemotherapy including pemetrexed platinum with measurable disease and good performance status, PS0 or 1. The patients were randomised to receive either anti-PD-1 nivolumab, 3mg/kg every two weeks, or nivolumab at the same dose plus ipilimumab, 1mg/kg every six weeks. The patients were treated until progression or unacceptable toxicity or a maximum of two years of treatment and they were reassessed by CT scan every twelve weeks. The first endpoint of the trial was the disease control rate at twelve weeks of treatment, secondary endpoints included assessment of overall survival, progression free survival, safety, toxicity and biomarkers.
We were able to recruit very quickly 125 patients in five months; most of these patients were male, in their 70s, good performance status, PS0 or 1, and with epithelioid subtype of mesothelioma. The compliance to the treatment was really good in both arms and the adverse events were rather mild, even if we observed slightly more severe adverse events in the combo group, 18% versus 10%. Three related deaths to the treatment were reported by local investigators in the nivo plus ipi group. In the first 180 eligible patients according to the statistical plan of the trial we assessed the first endpoint of the disease control rate and the target value was 40% in this trial. We were able to obtain 44% of disease control rate in the nivolumab arm and 50% in the nivo plus ipi arm. Moreover, we observed a shrinking of the tumour in 80% of the patients treated by nivo and 26% with nivo plus ipi.
This is the result after a limited median follow-up of 10.4 months. Mature progression free survival data show a very nice result of 5.6 months of PFS in the nivo plus ipi arm. I must remind you that with first line chemotherapy usually the PFS is around 6 months. We obtained 4 months in the nivo arm. More interestingly, in the primary median overall survival assessment we were able to measure the overall survival of 10.4 months with nivolumab and a very outstanding result of a not reached value for the nivo plus ipi arm. Moreover, when you look at the patients with disease control of the cancer they have really exceptional overall survival.
In conclusion, in this trial we showed that both nivolumab alone but also the nivolumab plus ipi arm reached the first endpoint in second and third line malignant pleural mesothelioma patients, increasing meaningfully the twelve weeks disease control rate. Moreover, the patients from both arms of this study seemed to have a prolonged median overall survival compared to all previous reports in this setting. The toxicity was globally manageable, even if we report three potential treatment related deaths in the combo arm. The mature survival, quality of life, biomarker data and subgroup analysis will be presented next autumn, one year after accrual of the last patient.
In conclusion, we think that immunotherapy by nivolumab combined or not with ipilimumab may provide a new therapeutic option as second and third line treatment for these relapsing malignant pleural mesothelioma patients with very bad prognosis so far. Thank you very much for your attention.