Pleural mesothelioma: with immunotherapy plus chemo, survival lengthens

“I received chemotherapy and immunotherapy and my cancer disappeared. I haven’t received any treatment since September 2020 and I’m still in remission today.” They are the words of Joan Davis Provost, a patient who participated in the IND.227 study whose results were presented today during the American Society of Clinical Oncology (ASCO) annual meeting during the oral session dedicated to thoracic tumors. Hers is a testimony that brings good news to patients with pleural mesothelioma: that it is possible to lengthen survival by administering chemotherapy together with immunotherapy.

I study

Pleural mesothelioma is a type of cancer that develops in the tissue lining the lungs of which more than 30,000 new cases were diagnosed worldwide in 2020. The international Phase III study IND.227 evaluated the use of the immunotherapy drug pembrolizumab in combination with platinum chemotherapy and pemetrexed as first-line treatment for patients with unresectable advanced or metastatic pleural mesothelioma. “The data presented today demonstrates that the use of pembrolizumab as an adjunct to platinum and pemetrexed chemotherapy prolongs the survival of patients with inoperable advanced or metastatic pleural mesothelioma,” he said. Quincy Chumedical oncologist at the Cross Cancer Institute and the Canadian Cancer Trials Group (CCTG), one of the principal investigators of the study for IND.227.

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The increase in survival

Pembrolizumab is a drug directed against programmed death receptor-1 (PD-1) that works by increasing the body’s immune system’s ability to help detect and fight cancer cells. “The addition of pembrolizumab to pemetrexed-platinum chemotherapy resulted in significant improvements in overall survival, progression-free survival, and objective response rate compared to pemetrexed-platinum chemotherapy alone, regardless of expression.” of PD-L1, and therefore represents a new treatment option for patients with advanced pleural mesothelioma”. Pembrolizumab is already approved for use in a number of other cancers, such as non-small cell lung cancer, still in combination with pemetrexed and platinum-based chemotherapy, as well as for cancers such as melanoma, head and neck cancer, and others.

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The diagnostic delay

It is estimated that there were more than 26,000 deaths from the disease in 2020. Pleural mesothelioma is usually advanced and incurable when diagnosed and is related to asbestos exposure. Because it develops after a long latency period, the worldwide incidence of pleural mesothelioma is expected to continue to increase. “Unfortunately – explained Chu – in most patients pleural mesothelioma is diagnosed at an already advanced stage, when surgery is not an option and survival rates are low. Standard treatments with platinum-based chemotherapy and pemetrexed have been in use for almost 20 years and more effective treatments are needed; only recently have some studies shown that new drugs such as immunotherapies can improve outcomes.”

Patient testimonials

Patient Joan Davis Prevost is being treated by the doctor Marie Florescu from the Center hospitalier de l’Université de Montréal (CHUM) in Montreal, says: “I haven’t received any treatment since September 2020 and today I’m still in remission, I enjoy life and play golf whenever I can. I was sentenced to death, but this treatment completely changed my fate. I hope all mesothelioma patients have access to this combination to have a real chance of beating this cancer,” she says.

Same enthusiasm for Emi Bossio, lung cancer survivor and CCTG Lung Cancer Patient Representative. “Only in the last few years have there been changes in the standard of care for patients with pleural mesothelioma. The results of this study are expected to have a tangible and significant impact on patients’ lives, as they show an improvement in both progression-free survival and overall survival.”

Cooperative research

The study was funded by the Canadian Cancer Society (CCS); Merck supported the study by providing the immunotherapy drug pembrolizumab and additional funding. “IND.227 is an academic study conducted by cooperative groups, promoted by the Canadian Cancer Trials Group with our partners in Italy (INT-Naples) and France (IFCT), and has defined a new treatment option for patients with pleural mesothelioma. International academic collaborations like this represent an important strategy for studying new treatments that will improve the prognosis of our patients, especially in diseases such as pleural mesothelioma,” he commented. Penelope Bradburydirector of the CCTG’s Lung Disease Site Committee, Oncologist at the Princess Margaret Cancer Center in Toronto and one of the most active researchers in the study.

The risk factors

Exposure to asbestos is the leading risk factor for pleural mesothelioma. Although its use was banned 30 years ago in Italy, the incidence of mesothelioma is still increasing due to the latency between exposure and the disease. “Before the recent results obtained with immunotherapy – he says Francesco Perrone, also principal investigator of the study, Director of the Clinical Trials Unit of the National Cancer Institute of Naples IRCCS Fondazione G. Pascale, President Elect of the Italian Association of Medical Oncology (AIOM), and coordinator of the Italian cooperative group involved in the study – chemotherapy was the only treatment available for 20 years, with disappointing results. Participation in this study was an excellent opportunity for Italian patients, as demonstrated by the large participation, in fact, almost half of the patients in the study are Italian. Adding pembrolizumab to chemotherapy in study IND.227 improved survival, progression-free survival, and objective response rates, with no findings of toxicity that weren’t already expected. Pembrolizumab in combination with platinum chemotherapy and pemetrexed represents a new treatment option for patients with inoperable advanced pleural mesothelioma.”

No more orphan disease

While pleural mesothelioma was considered a deadly orphan disease just a few decades ago, significant progress has recently been achieved through clinical research efforts and international collaborations. “The results of the IND.227 study represent one such advance and now offer another valuable treatment option for patients with pleural mesothelioma,” he says Laurent Greillier, president of the French Thoracic Cooperative Intergroup, IFCT, Director of the Department of Multidisciplinary Oncology and Therapeutic Innovations of the Publique Assistance – Hôpitaux de Marseille of the Aix University of Marseille. “We are proud to support the CCTG and excited that the positive results of this study have the potential to improve patient outcomes,” said Stuart Edmonds, Executive Vice President of Mission, Research and Advocacy at the Canadian Cancer Society. “With the help of our generous donors, we look forward to funding more international clinical trials like this that benefit so many people living with cancer in our country and around the world.”

The results of the IND.227 study

At the final analysis of the study, pembrolizumab added to chemotherapy significantly improved overall survival, reducing the risk of death by 21%. 3-year survival was better for patients treated with pembrolizumab plus platinum chemotherapy and pemetrexed than for those treated with platinum chemotherapy and pemetrexed alone (25% vs. 17%, respectively, of patients alive at 3 years). Progression-free survival was also significantly better. Objective response rates were significantly higher (62% for the pembrolizumab and chemotherapy arm and 38% for the chemotherapy alone arm. Severe adverse events (Grade 3 or 4) occurred in 27% of patients treated with pembrolizumab and chemotherapy with platinum and pemetrexed and in 15% of patients treated with chemotherapy with platinum and pemetrexed alone.