The next generation of immunotherapy: keeping lung cancer in check

Our plain-English summary of The next generation of immunotherapy: keeping lung cancer in check, by A. Somasundaram, T.F. Burns (Journal of Hematology & Oncology, 2017).

The study

• Authors: A. Somasundaram, T.F. Burns
• Journal: Journal of Hematology & Oncology
• Published: 2017;10(1):87
• Type of article: Review
• Cited by: 87 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Lung cancer is the deadliest malignancy with more cancer deaths per year than the next three cancers combined. Despite remarkable advances in targeted therapy, advanced lung cancer patients have not experienced a significant improvement in mortality. Lung cancer has been shown to be immunogenic and responsive to checkpoint blockade therapy. Checkpoint signals such as CTLA-4 and PD-1/PD-L1 dampen T cell activation and allow tumors to escape the adaptive immune response. Response rates in patients with pretreated, advanced NSCLC were much higher and more durable with PD-1 blockade therapy compared to standard-of-care, cytotoxic chemotherapy. Therefore, PD-1 inhibitors such as nivolumab and pembrolizumab were rapidly approved for both squamous and nonsquamous lung cancer in the pretreated population. The advent of these new therapies have revolutionized the treatment of lung cancer; however, the majority of NSCLC patients still do not respond to PD-1/PD-L1 inhibition leaving an unmet need for a large and growing population.Immunotherapy combinations with chemotherapy, radiation therapy, or novel immunomodulatory agents are currently being examined with the hope of achieving higher response rates and improving overall survival rate. Chemotherapy and radiation therapy has been theorized to increase the release of tumor antigen leading to increased responses with immunotherapy. However, cytotoxic chemotherapy and radiation therapy may also destroy actively proliferating T cells. The correct combination and order of therapy is under investigation. The majority of patients who do respond to immunotherapy have a durable response attributed to the effect of adaptive immune system's memory. Unfortunately, some patients' tumors do progress afterward and investigation of checkpoint blockade resistance is still nascent.This review will summarize the latest efficacy and safety data for early and advanced NSCLC in both the treatment-naïve and pretreated settings. The emerging role of immunotherapy for the treatment of small cell lung cancer and malignant mesothelioma will also be discussed.

In plain English

This article was a review, not a new study. The authors summarized clinical trials of checkpoint-inhibitor immunotherapy drugs, mainly in non-small cell lung cancer (NSCLC), with shorter sections on small cell lung cancer and malignant mesothelioma. It did not study asbestos exposure. Among the trials reviewed, CheckMate 017 reported median overall survival of 9.2 months (95% CI 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI 5.1 to 7.3) with docetaxel chemotherapy in advanced, previously treated squamous NSCLC. KEYNOTE-024 reported median progression-free survival of 10.3 months (95% CI 6.7 to not reached) with pembrolizumab versus 6.0 months (95% CI 4.2 to 6.2) with chemotherapy in untreated, advanced NSCLC with at least 50% PD-L1 expression. For mesothelioma, the DETERMINE trial found no difference in overall survival between tremelimumab and placebo (7.7 versus 7.3 months). In the JAVELIN avelumab trial, response rates were 14.3% in PD-L1-positive and 8.0% in PD-L1-negative tumors. The authors noted that long-term survival data were immature and most NSCLC patients still do not respond. They concluded that immunotherapy for mesothelioma was promising but still early.

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: Review of published and ongoing clinical trials of checkpoint-inhibitor immunotherapy
• Who was studied: Trials in patients with early and advanced non-small cell lung cancer (previously treated and treatment-naive), small cell lung cancer, and malignant mesothelioma, as reported in the referenced publications
• Exposure: Checkpoint-inhibitor drugs: PD-1 inhibitors (nivolumab, pembrolizumab), PD-L1 inhibitors (atezolizumab, durvalumab, avelumab) and CTLA-4 inhibitors (ipilimumab, tremelimumab), alone or combined with chemotherapy or other agents. Asbestos exposure was not studied.
• Main results:
  • Reviewed CheckMate 017 trial (advanced, previously treated squamous NSCLC): median overall survival was 9.2 months (95% CI 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI 5.1 to 7.3) with docetaxel
  • Reviewed KEYNOTE-024 trial (treatment-naive advanced NSCLC with at least 50% PD-L1 expression): median progression-free survival was 10.3 months (95% CI 6.7 to not reached) with pembrolizumab versus 6.0 months (95% CI 4.2 to 6.2) with chemotherapy
  • Reviewed DETERMINE phase 2 trial (previously treated malignant mesothelioma): no difference in overall survival between tremelimumab and placebo, 7.7 versus 7.3 months (HR 0.92, 95% CI 0.76 to 1.12, p = 0.408)
  • Reviewed JAVELIN phase 1b trial of avelumab (previously treated, unresectable malignant mesothelioma, 53 patients at interim analysis): overall response rate was 14.3% in PD-L1-positive tumors versus 8.0% in PD-L1-negative tumors
• The authors' conclusion: The authors concluded that immunotherapy as a new treatment for mesothelioma is promising but still early
• Limitations the authors state:
  • The authors stated that long-term survival data are still too immature to judge the overall impact of immunotherapy on lung cancer prognosis
  • The authors stated that most NSCLC patients still do not respond to PD-1/PD-L1 inhibition

Topics

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

Medical terms in this study, explained in our Lexicon: Immunotherapy, Lung Cancer, Targeted Therapy, CTLA-4, PD-1/PD-L1, Chemotherapy, Nivolumab (Opdivo), Pembrolizumab (Keytruda).

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• Is there a role for immunotherapy in malignant pleural mesothelioma? — A. Tartarone, R. Lerose, et al. (2018)
• Anti-CTLA-4 therapy for malignant mesothelioma — A. Guazzelli, E. Bakker, et al. (2017)
• PD-1/PD-L1 Checkpoint Inhibitor Immunotherapy for Malignant Pleural Mesothelioma: Case Series and Literature Review — M. Zhou, N. Joshi, et al. (2021)
• Use of Neoadjuvant Immunotherapy in Malignant Peritoneal Mesothelioma as a Bridge to Surgical Intervention: A Case Report — S. Faleh, T. Odisho, et al. (2025)
• Exposing Hidden Targets: Combining epigenetic and immunotherapy to overcome cancer resistance — K. Olino, T. Park, et al. (2020)

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