Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC

Our plain-English summary of Old but gold: the role of drug combinations in improving response to immune check-point inhibitors in thoracic malignancies beyond NSCLC, by L. Cantini, F. Pecci, F. Merloni, et al (Exploration of Targeted Anti-tumor Therapy, 2021).

The study

• Authors: L. Cantini, F. Pecci, F. Merloni, A. Lanese, E. Lenci, F. Paoloni, J.G.J.V. Aerts, R. Berardi
• Journal: Exploration of Targeted Anti-tumor Therapy
• Published: 2021;2(1):1-25
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The introduction of immune checkpoint inhibitors (ICIs) in non-oncogene addicted non-small cell lung cancer (NSCLC) has revolutionized the treatment scenario and led to a meaningful improvement in patient prognosis. Disappointingly, the success of ICI therapy in NSCLC has not been fully replicated in other thoracic malignancies as small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM), and thymic epithelial tumors (TETs), due to the peculiar biological features of these disease and to the difficulties in the conduction of well-designed, biomarker-driven clinical trials. Therefore, combination strategies of ICIs plus conventional therapies (either chemotherapy, alternative ICIs or targeted agents) have been implemented. Although first approvals of ICI therapy have been recently granted in SCLC and MPM (in combination with chemotherapy and different ICIs), results remain somewhat modest and limited to a small proportion of patients. This work reviews the trial results of ICI therapy in mesothelioma, SCLC, and TETs and discusses the potential of combining ICIs with old drugs.

© The Author(s) 2021.

In plain English

This article was a review, not a new study. The authors examined clinical trial results for immune checkpoint inhibitor drugs in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumors. They also listed ongoing trials and discussed combining these drugs with chemotherapy, other immune drugs or targeted drugs. As background, the article noted that malignant pleural mesothelioma is most commonly caused by exposure to mineral fibers such as asbestos and erionite. The article did not itself study exposure. Among the mesothelioma trials described, an interim analysis of CheckMate-743 enrolled 605 patients with unresectable disease. It reported significantly longer median overall survival as first treatment with nivolumab plus ipilimumab (18.1 months) than with chemotherapy (14.1 months). In a large randomized mesothelioma trial, tremelimumab alone gave a median survival of 7.7 months versus 7.3 months with placebo. The authors concluded that single-drug immunotherapy had remained below expectations. They added that combinations might help overcome resistance and widen the group of thoracic cancer patients who benefit from immunotherapy.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published (including conference-presented) clinical trials, with tables of ongoing trials from ClinicalTrials.gov
• Who was studied: No patients of its own. The review covered trials in patients with small cell lung cancer (SCLC), malignant pleural mesothelioma (MPM) and thymic epithelial tumors (TETs).
• Exposure: Not an exposure study. The treatments reviewed were immune checkpoint inhibitors (ICIs), alone or combined with chemotherapy, other ICIs, anti-angiogenic drugs or PARP inhibitors. As background, the article states that MPM is most commonly caused by exposure to mineral fibers such as asbestos and erionite.
• Main results:
  • MPM, CheckMate-743 (prespecified interim analysis, first-line, unresectable MPM): 605 patients enrolled. At a median follow-up of 29.7 months, median overall survival was significantly longer with nivolumab plus ipilimumab (18.1 months) than with chemotherapy (14.1 months).
  • MPM, MAPS2 phase II trial (after first-line therapy): median overall survival was 11.9 months with nivolumab alone and 15.9 months with nivolumab plus ipilimumab.
  • MPM: tremelimumab (an anti-CTLA4 antibody) did not show a benefit over placebo in a large randomized trial. Median overall survival was 7.7 months with tremelimumab versus 7.3 months with placebo.
  • MPM with disease recurrence, randomized study of pembrolizumab versus chemotherapy (gemcitabine or vinorelbine): the two groups had almost equal PFS (2.5 vs. 3.4) and OS (10.7 vs. 11.7). Units are not stated in the text.
  • MPM, MAPS phase III trial (no ICI): adding bevacizumab to cisplatin and pemetrexed significantly increased median overall survival, 18.8 vs. 16.1 months, P = 0.0167.
  • MPM, PrE0505 phase II trial: durvalumab with cisplatin and pemetrexed in 55 previously untreated patients with unresectable MPM reached its primary endpoint, with median overall survival of 20.4 months (P = 0.0014, one-sided).
  • Mesothelioma, NIBIT-MESO-1 phase II trial of tremelimumab plus durvalumab: the trial enrolled patients with malignant pleural and peritoneal mesothelioma (the article writes 'peritoneal MPM'). Results were ORR 28%, DCR 65%, median PFS 8 months and median OS 16.6 months.
  • SCLC, IMpower133 phase III trial in untreated extensive-stage SCLC: median OS was 12.3 months with atezolizumab plus carboplatin and etoposide versus 10.3 months with chemotherapy plus placebo (P = 0.007, HR 0.70).
  • Thymic carcinoma, single-arm phase 2 pembrolizumab study (after at least one line of chemotherapy): 22.5% of patients responded. Six (15%) patients developed severe autoimmune toxicity, including two (5%) with myocarditis.
  • Overall, the authors judged that single-agent ICI benefit in SCLC, MPM and TETs had remained below expectations.
• The authors' conclusion: The authors concluded that combining ICIs with chemotherapy, other ICIs (such as anti-CTLA4 drugs) or targeted therapies might help overcome resistance. They concluded this might also broaden the group of thoracic cancer patients who benefit from immunotherapy.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Non-Small Cell Lung Cancer, Prognosis, Small Cell Lung Cancer, Pleural Mesothelioma, Biomarker, Clinical Trial, Chemotherapy.

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