New treatments for mesothelioma 2022
New treatments for mesothelioma 2022
Newly diagnosed mesothelioma
For the last two decades, chemotherapy (pemetrexed and cisplatin or carboplatin) has been the main treatment for patients with newly diagnosed mesothelioma with published effectiveness of 23% reduction in the risk of death compared to cisplatin alone.[1] However, patients can relapse and (until now) treatment options were limited.
An international multi-center trial CHECKMATE-743 trial compared the two immunotherapy agents given together (ipilimumab and nivolumab) against chemotherapy (pemetrexed and carboplatin or cisplatin) reporting a 26% reduction in the risk of death. Using both immunotherapies were particularly effective in patients with the more aggressive subgroup of mesothelioma known as non-epithelioid (includes sarcomatoid and biphasic mesothelioma) with a 54% reduction in risk of death. Serious side effects (that increased hospital stay or resulted in death) was higher for immunotherapy (21% compared to the 8% for those receiving chemotherapy). [2] Ipilimumab and nivolumab is licensed by the FDA and EMA and currently under review by NICE in the UK.
Despite the innovation in treatments with combination immunotherapy, the average duration of diease control is approximately 6 months. As with chemotherapy, it is expected that most patients will relapse can continue to grow quickly (compared to chemotherapy alone). Currently, no therapy is licenced in the setting of realpsed mesothelioma. Clinical trials are therefore ongoing to explore new single agent and combination therapies that could control mesothelioma.
Relapsed mesothelioma
At the ASCO 2021 meeting, results from the VIM trial that randomized patients with relapsed mesothelioma to vinorelbine (a type of chemotherapy) or best supportive care were reported that the addition of vinorelbine improved disease control. In the UK, vinorelbine is accessible via the NHS and has been a de facto treatment (although not specifically licenced in this setting).
A randomsied clinical trial called PROMISE-MESO trial compared immunotherapy (pembrolizumab) or chemotherapy (gemcitabine or vinorelbine) concluded for participants with relapsed mesothelioma, pembolizumab alone was not associated with any difference in cancer progression or survival.[3]
At the World Conference of Lung Cancer in 2021, findings of the CONFIRM trial comparing immunotherapy (nivolumab) against placebo in patients with relapsed mesothelioma were reported showing a 28% reduction in the risk of death with nivolumab.[4] The drug was well tolerated and although recommended for use in international (NCCT and ESMO) guidelines, it is not yet licensed.
Putting the above advances together, for patients with relapsed mesothelioma, immunotherapy is effective and improves survival of patients with relapsed mesothelioma and may be equally effective compared with chemotherapy.
The author of the article Dr Wanda Cui has received funding from Janssen that manufactures amivantamab.
References
[1] Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, Niyikiza C and Paoletti P. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. Journal of Clinical Oncology. 2003;21:2636-2644.
[2] Baas P, Scherpereel A, Nowak AK, Fujimoto N, Peters S, Tsao AS, Mansfield AS, Popat S, Jahan T, Antonia S, Oulkhouir Y, Bautista Y, Cornelissen R, Greillier L, Grossi F, Kowalski D, Rodríguez-Cid J, Aanur P, Oukessou A, Baudelet C and Zalcman G. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397:375-386.
[3] Popat S, Curioni-Fontecedro A, Dafni U, Shah R, O'Brien M, Pope A, Fisher P, Spicer J, Roy A, Gilligan D, Gautschi O, Nadal E, Janthur WD, López Castro R, García Campelo R, Rusakiewicz S, Letovanec I, Polydoropoulou V, Roschitzki-Voser H, Ruepp B, Gasca-Ruchti A, Peters S and Stahel RA. A multicentre randomised phase III trial comparing pembrolizumab versus single-agent chemotherapy for advanced pre-treated malignant pleural mesothelioma: the European Thoracic Oncology Platform (ETOP 9-15) PROMISE-meso trial. Annals of Oncology. 2020;31:1734-1745.
[4] Fennell DA, Ewings S, Ottensmeier C, Califano R, Hanna GG, Hill K, Danson S, Steele N, Nye M, Johnson L, Lord J, Middleton C, Szlosarek P, Chan S, Gaba A, Darlison L, Wells-Jordan P, Richards C, Poile C, Lester JF, Griffiths G, Price G, Shaw P, Cave J, Naik J, Ford A, Geldhart T, Dancey G, Papadatos D, Polychronis A, Jankowska P, Scott A, Gardiner J, Cominos M, Campbell L, MacGregor C, Mullholand L, Chitnis M and Dougherty G. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. The Lancet Oncology.
Amended (for clarity following patient review) 8 December 2021