Progress in the Management of Advanced Thoracic Malignancies in 2017

Our plain-English summary of Progress in the Management of Advanced Thoracic Malignancies in 2017, by R. Ferrara, L. Mezquita, B. Besse (Journal of Thoracic Oncology, 2018).

The study

• Authors: R. Ferrara, L. Mezquita, B. Besse
• Journal: Journal of Thoracic Oncology
• Published: 2018;13(3):301-322
• Type of article: Historical article, Review
• Cited by: 40 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The treatment paradigm of NSCLC underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival both in unselected pretreated patients and in untreated patients with programmed death ligand 1 expression of 50% or more. Furthermore, compelling preliminary results were reported for new combinations of anti-programmed cell death 1/programmed death ligand 1 agents with chemotherapy or anti-cytotoxic T-lymphocyte associated protein 4 inhibitors. The success of the ICIs appeared to extend to patients with SCLC, mesothelioma, or thymic tumors. Furthermore, in SCLC, encouraging activity was reported for an experimental target therapy (rovalpituzumab teserine) and a new chemotherapeutic agent (lurbinectedin). For oncogene-addicted NSCLC, next-generation tyrosine kinase inhibitors (TKIs) (such as osimertinib or alectinib) have demonstrated increased response rates and progression-free survival compared with first-generation TKIs in patients with both EGFR-mutated and ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC. However, because of the lack of mature overall survival data and considering the high efficacy of these drugs in patients with NSCLC previously exposed to first- or second-generation TKIs, definitive conclusions concerning the best treatment sequence cannot yet be drawn. In addition, new oncogenes such as mutant BRAF, tyrosine-protein kinase met gene (MET) and erb-b2 receptor tyrosine kinase 2 gene (HER2), and ret proto-oncogene (RET) rearrangements have joined the list of potential targetable drivers. In conclusion, the field of thoracic oncology is on the verge of a breakthrough that will open up many promising new therapeutic options for physicians and patients. The characterization of biomarkers predictive of sensitivity or resistance to immunotherapy and the identification of the optimal therapeutic combinations (for ICIs) and treatment sequence (for oncogene-addicted NSCLC) represent the toughest upcoming challenges in the domain of thoracic oncology.

Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

In plain English

This was a review that summarized earlier clinical trials and cohort studies rather than presenting new data. The authors searched 2017 PubMed citations and conference abstracts on treating advanced non-small cell and small cell lung cancer, malignant pleural mesothelioma (MPM) and thymic tumors. It did not address asbestos or other causes of these cancers. In the MAPS2 trial, previously treated MPM patients received nivolumab or nivolumab plus ipilimumab in two arms not designed to be compared, and 12-week disease control rates were 44% and 50%. DETERMINE found no significant overall survival difference between tremelimumab and placebo. In KEYNOTE-028, pembrolizumab gave a 20% response rate (95% CI 6.8 to 40.7) in 25 previously treated MPM patients with PD-L1 expression of 1% or higher. In LUME-Meso (epithelioid or biphasic MPM), adding nintedanib to platinum-pemetrexed gave progression-free survival of 9.4 versus 5.7 months, mainly in epithelioid disease, with only a nonsignificant overall survival trend. The authors concluded that several 2017 studies reshaped treatment of advanced non-small cell lung cancer. Treatment of MPM, small cell lung cancer and thymic tumors did not change in any major way, though immune checkpoint inhibitors showed compelling results in MPM.

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 and cohort studies published or presented in 2017
• Who was studied: Published studies and conference presentations from January to December 2017 on patients with thoracic cancers: NSCLC, small cell lung cancer, malignant pleural mesothelioma and thymic tumors
• Exposure: No asbestos or other environmental or occupational exposure was studied. The review concerned cancer treatments: immune checkpoint inhibitors, targeted therapies and chemotherapy.
• Main results:
  • In the MAPS2 phase II trial (reviewed), 125 patients with pretreated advanced mesothelioma were randomized to nivolumab or nivolumab plus ipilimumab, in two arms that were not designed to be compared. Disease control rates at 12 weeks were 44% with nivolumab and 50% with the combination. Median progression-free survival was 4.0 and 5.6 months, and median overall survival was 10.4 months and not reached, respectively.
  • In the DETERMINE phase IIb trial (reviewed), 569 patients with advanced MPM received treatment: 380 got tremelimumab and 189 got placebo. There was no significant difference in overall survival (7 to 8 months in both arms), and tremelimumab caused more toxicity.
  • In the KEYNOTE-028 phase Ib trial (reviewed), 25 patients with previously treated MPM and PD-L1 expression of 1% or higher received pembrolizumab. The response rate was 20% (95% CI 6.8 to 40.7) and the disease control rate was 72%.
  • In the LUME-Meso phase II trial (reviewed), patients with epithelioid or biphasic MPM received nintedanib or placebo, each with platinum-pemetrexed. Progression-free survival was 9.4 months with nintedanib versus 5.7 months with placebo (p = 0.01), mainly in the epithelioid type. Response rates were 57% versus 44%. Overall survival (18 versus 14 months) showed only a nonsignificant trend.
  • In the TRAP phase I expansion cohort (reviewed), ADI-PEG20 plus cisplatin-pemetrexed was given in MPM with loss of argininosuccinate synthase 1. It produced a response rate of 35%, progression-free survival of 5.6 months and overall survival of 10.1 months. Serious blood-related side effects occurred in around 30% of patients.
  • In NSCLC with PD-L1 expression of 50% or higher (a reviewed trial), first-line pembrolizumab compared with platinum chemotherapy gave response rates of 45.5% versus 29.8% and median overall survival of 30 versus 14.2 months.
• The authors' conclusion: The authors concluded that several 2017 studies reshaped treatment of advanced NSCLC. Treatment of small cell lung cancer, MPM and thymic tumors did not change in any major way in 2017, although immune checkpoint inhibitors showed compelling results in MPM and thymic tumors.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Overall Survival, Chemotherapy, Mesothelioma, Tyrosine Kinase Inhibitor, Progression-Free Survival, EGFR, HER2.

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