Role of Immunotherapy in Small Cell Lung Cancer, Thymic Epithelial Tumors, and Mesothelioma

Our plain-English summary of Role of Immunotherapy in Small Cell Lung Cancer, Thymic Epithelial Tumors, and Mesothelioma, by C.L. Hann, A. Scherpereel, J.A. Hellyer, et al (American Society of Clinical Oncology Educational Book, 2019).

The study

• Authors: C.L. Hann, A. Scherpereel, J.A. Hellyer, H.A. Wakelee
• Journal: American Society of Clinical Oncology Educational Book
• Published: 2019;39:543-552
• Type of article: Review
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The introduction of programmed death receptor ligand-1 (PD-L1) and programmed death receptor-1 (PD-1) inhibitors into the field of non-small cell lung cancer (NSCLC) was practice changing. The pivotal trials consistently showed a clinically meaningful improvement in overall survival (OS) for patients with driver mutation-negative NSCLC, a field in which outcomes had been stagnant for decades. The success of immune checkpoint inhibitor (ICI) therapy in NSCLC has led to enthusiasm to expand the reach of these drugs into other thoracic malignancies such as thymic epithelial tumors (TETs), mesothelioma, and small cell lung cancer (SCLC). Unfortunately, the improvement in outcomes with ICI therapy in these rarer thoracic tumors has been somewhat modest, and in the case of thymoma, rates of adverse events are too high to routinely justify their use. Although the response rates seen in ICI therapy in these tumor types are similar to those seen with other available single-agent therapies for advanced disease, ICIs do present another option for clinicians treating patients with mesothelioma, small cell carcinoma, and thymic carcinoma (TC), diseases in which approved treatment options are limited. Here we review the latest trials of ICI therapy in mesothelioma, SCLC, and TETs.

In plain English

This article was a review. The authors reviewed trials of immune checkpoint inhibitor drugs in small cell lung cancer, thymic epithelial tumors and mesothelioma. The article states malignant pleural mesothelioma is usually associated with previous asbestos exposure. In mesothelioma, DETERMINE found no benefit from tremelimumab: median overall survival was 7.7 months versus 7.3 months with placebo (hazard ratio 0.92; p = 0.408). In MAPS-2, 125 patients whose pleural mesothelioma had resisted pemetrexed/platinum chemotherapy received nivolumab alone or with ipilimumab. Median overall survival was 11.9 months (95% CI, 6.7 to 17.7) and 15.9 months (95% CI, 10.7 to not reached) respectively. In IMpower133, among 403 patients with newly diagnosed extensive-stage small cell lung cancer, adding atezolizumab to first-line chemotherapy gave median overall survival of 12.3 versus 10.3 months (hazard ratio 0.70). In a Korean trial, treatment of the thymoma group was stopped after five of the first seven patients developed severe immune-related side effects. The authors concluded that these drugs look promising as salvage therapy for advanced refractory pleural mesothelioma, but that more data are needed for frontline or early-stage disease.

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 clinical trials of immune checkpoint inhibitors (educational book chapter). The article does not describe how the trials were selected.
• Who was studied: Patients enrolled in published or conference-reported trials of immune checkpoint inhibitors for small cell lung cancer, thymic epithelial tumors and mesothelioma. Most mesothelioma trials were in malignant pleural mesothelioma, and some also included peritoneal mesothelioma.
• Exposure: This was not an asbestos exposure study. The treatments reviewed were immune checkpoint inhibitor drugs (for example pembrolizumab, nivolumab, ipilimumab, tremelimumab, durvalumab and atezolizumab). Asbestos is mentioned only as the usual association of malignant pleural mesothelioma.
• Main results:
  • DETERMINE trial (564 patients with mesothelioma, second or third line): tremelimumab versus placebo gave a median overall survival of 7.7 versus 7.3 months (hazard ratio 0.92; p = 0.408). The review reports this as no benefit.
  • KEYNOTE-028 (25 patients with PD-L1-positive malignant pleural mesothelioma treated with pembrolizumab, mostly second line): objective response rate was 20% (95% CI, 6.8 to 40.7), and 52% of patients had stable disease.
  • NIBIT-MESO-1 (tremelimumab plus durvalumab, first or second line, unresectable pleural or peritoneal mesothelioma): 11 of 40 patients (27.5%) had an immune-related partial response. Median overall survival was 16.6 months (95% CI, 13.1 to 20.1).
  • MAPS-2 (125 patients with malignant pleural mesothelioma refractory to pemetrexed/platinum chemotherapy): disease control at 12 weeks was 50% with nivolumab plus ipilimumab versus 44.4% with nivolumab alone.
  • MAPS-2: median overall survival was 11.9 months (95% CI, 6.7 to 17.7) with nivolumab and 15.9 months (95% CI, 10.7 to not reached) with nivolumab plus ipilimumab. There were zero toxic deaths in the nivolumab arm and three (4.8%) in the combination arm.
  • INITIATE (nivolumab plus ipilimumab after platinum chemotherapy, 34 evaluable patients): disease control at 12 weeks was 68% (95% CI, 50 to 83). Grade 3 treatment-related adverse events occurred in 12 patients (34%), and there were no treatment-related deaths.
  • DREAM (durvalumab with cisplatin/pemetrexed in untreated, unresectable malignant pleural mesothelioma; updated results in 54 patients): median progression-free survival was 6.2 months, and 57% of patients were free of progression at 6 months.
  • IMpower133 (403 patients with newly diagnosed extensive-stage small cell lung cancer): median overall survival was 12.3 months with atezolizumab plus chemotherapy versus 10.3 months with chemotherapy plus placebo (hazard ratio 0.70).
  • Korean pembrolizumab trial in thymic epithelial tumors: treatment of the thymoma cohort was stopped after five of the first seven enrolled patients developed severe immune-related adverse events.
• The authors' conclusion: The authors concluded that immune checkpoint inhibition looks promising as salvage therapy for advanced refractory malignant pleural mesothelioma. They said further data are needed to assess its role in frontline or early-stage disease, and that more work is needed to understand which patients are likely to benefit with the least toxicity.
• Limitations the authors state:
  • The authors state that many questions remain about immunotherapy in mesothelioma. They say further phase II and phase III trials are needed to establish it and to validate biomarkers for selecting patients.
  • The authors note that the data from the DREAM mesothelioma trial remain immature.
  • The authors note that results of neoadjuvant immunotherapy studies (treatment given before surgery) in resectable malignant pleural mesothelioma have not yet been published.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Immunotherapy, Small Cell Lung Cancer, Mesothelioma, PD-L1, Non-Small Cell Lung Cancer, Overall Survival, checkpoint inhibitors, Carcinoma.

Related studies

• Primary thymic epithelial tumours of the pleura mimicking malignant mesothelioma — R.L. Attanoos, F. Galateau-Salle, et al. (2002)
• Immunotherapy in relapsed mesothelioma — S. Brosseau, X. Dhalluin, et al. (2018)
• Mesothelioma and small cell lung cancer — A.S. Tsao, J. Heymach (2011)
• Systemic approach to malignant pleural mesothelioma: what news of chemotherapy, targeted agents and immunotherapy? — D. Signorelli, M. Macerelli, et al. (2016)
• Primary small cell carcinoma of the pleura: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes — T. Terada (2010)
• Complete heart block ensuing from a metastatic small cell carcinoma: a case report — P. Pallangyo, G. Kweka, et al. (2022)

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