Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jun 17;4(3):e000498.
doi: 10.1136/esmoopen-2019-000498. eCollection 2019.

Immune checkpoint inhibitor treatment in patients with oncogene- addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion

Anna S Berghoff  1 , Beatriz Bellosillo  2 , Christophe Caux  3 , Adrianus de Langen  4 , Julien Mazieres  5 , Nicola Normanno  6 , Matthias Preusser  1 , Mariano Provencio  7 , Federico Rojo  8 , Jurgen Wolf  9 , Christoph C Zielinski  10   11
Affiliations
Review

Immune checkpoint inhibitor treatment in patients with oncogene- addicted non-small cell lung cancer (NSCLC): summary of a multidisciplinary round-table discussion

Anna S Berghoff et al. ESMO Open. .

Abstract

The introduction of targeted treatments and more recently immune checkpoint inhibitors (ICI) to the treatment of metastatic non-small cell lung cancer (NSCLC) has dramatically changed the prognosis of selected patients. For patients with oncogene-addicted metastatic NSCLC harbouring an epidermal growth factor receptor (EGFR) or v-Raf murine sarcoma viral oncogene homologue B1 (BRAF) mutation or an anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene alteration (translocation, fusion, amplification) mutation-specific tyrosine kinase inhibitors (TKI) are already first-line standard treatment, while targeted treatment for other driver mutations affecting MET, RET, human epidermal growth factor receptor (HER) 2, tropomyosin receptor kinases (TRK) 1-3 and others are currently under investigation. The role of ICI in these patient subgroups is currently under debate. This article summarises a round-table discussion organised by ESMO Open in Vienna in July 2018. It reviews current clinical data on ICI treatment in patients with metastatic oncogene-addicted NSCLC and discusses molecular diagnostic assessment, potential biomarkers and radiological methods for response evaluation of ICI treatment. The round-table panel concluded ICI should only be considered in patients with oncogene-addicted NSCLC after exhaustion of effective targeted therapies and in some cases possibly after all other therapies including chemotherapies. More clinical trials on combination therapies and biomarkers for ICI therapy based on the specific differing characteristics of oncogene-addicted NSCLC need to be conducted.

Keywords: NSCLC; immune checkpoint inhibitors; oncogene addiction.

PubMed Disclaimer

Conflict of interest statement

Competing interests: ASB: Travel support: Daiichi Sankyo, Bristol-Meyers Squibb, Roche, Amgen, Merck, AbbVie; Research Support: Daiichi Sankyo; Advisory Board: Roche. BB: Travel support: Bristol-Meyers Squibb, Roche, Merck; Research support: Roche, Pfizer, Novartis; Advisory Board: Roche, Novartis; Speaker: AstraZeneca, Pfizer, Roche. AJdL: Related to this work: none; in general: Advisor for AstraZeneca, BMS, Boehringer, Pfizer, MSD, Roche; research grants from AstraZeneca, BMS, Merck-Serono, MSD, Roche. JM: Travel support: MSD, MSD, Roche; Research support: Roche, Astra-Zeneca; Advisory Board: Roche, MSD, BMS, Takeda, Astra-Zeneca, Pharmamar, Boehringer. NN: Personal financial interests (speaker’s fee and/or advisory boards): MSD, Qiagen, Biocartis, Incyte, Roche, BMS, MERCK, Thermofisher, Boehringer Ingelheim, Astrazeneca, Sanofi, Eli Lilly; Institutional financial interests (financial support to research projects): MERCK, Sysmex, Thermofisher, QIAGEN, Roche, Astrazeneca, Biocartis; non-financial interests: President, International Quality Network for Pathology (IQN Path); President Elect, Italian Cancer Society (SIC). MP: Personal fees from BMS, Astra Zeneca, Pierre Fabre, Roche, Novartis and Takeda. MP: Received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Merck Sharp & Dome. FR: Travel support: Roche, Merck, Pfizer. Scientific advisor: Genomic Health, Roche, Guardant Health, Merck, Pfizer, Bristol-Meyers Squibb, Abbvie, Astra Zeneca, Novartis. JW: Advisory boards and lecture fees: Abbvie, AstraZeneca, BMS, Boehringer-Ingelheim, Chugai, Ignyta, Lilly, MSD, Novartis, Pfizer, Roche; research support (to institution): BMS, MSD, Novartis, Pfizer. CZ: Roche, Novartis, BMS, MSD, Imugene, Ariad, Pfizer, Merrimack/Shire, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Eli Lilly, Amgen.

Figures

Figure 1
Figure 1
Molecular testing parallel algorithm without next generation sequencing (adapted from Kerr and López-Ríos17). ALK, anaplastic lymphoma kinase; EGFR, epidermal growth factor receptor; FISH, fluorescence in situ hybridisation; ICI, immune checkpoint inhibitor; MDT, multidisciplinary team; NSCLC, non-small cell lung cancer; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; TKI, tyrosine kinase inhibitor
Figure 2
Figure 2
Molecular testing algorithm when NGS is commonplace (adapted from Kerr and López-Rios17). MDT, multidisciplinary team; NSCLC, non-small cell lung cancer; NGS, next generation sequencing; PD-L1, programmed death-ligand 1; TMB, tumour mutational burden.
Figure 3
Figure 3
Relationship of programmed death-ligand 1 (PD-L1) expression with oncogene alterations.
Figure 4
Figure 4
Relationship between mutational load and response to immunotherapies targeting PD-1/PD-L1. Reprinted by permission from Springer Nature. Yarchoan M, Johnson III BA, Lutz ER et al. Targeting neoantigens to augment antitumour immunity. Nat Rev Cancer 2017. NSCLC, non-small cell lung carcinoma; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1; RCC, renal cell carcinoma; SCLC, small cell lung carcinoma.
Figure 5
Figure 5
Response after durvalumab treatment in cohort 1 of the ATLANTIC trial (EGFR+/ALK+). Reprinted with permission from Elsevier. DOR, duration of response; OS, overall survival; PFS, progression-free survival; TTR, time to response.
Figure 6
Figure 6
Comparison of key differences in Response Evaluation Criteria in Solid Tumours (RECIST) V.1.1 and immune-related response criteria (irRC). Reprinted with permission from American Society of Clinical Oncology, Copyright 2016. All rights reserved.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Barlesi F, Mazieres J, Merlio J-P, et al. . Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative thoracic intergroup (IFCT). The Lancet 2016;387:1415–26. 10.1016/S0140-6736(16)00004-0 - DOI - PubMed
    1. Novello S, Barlesi F, Califano R, et al. . Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up†. Ann Oncol 2016;27:v1–27. 10.1093/annonc/mdw326 - DOI - PubMed
    1. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. . Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med 2018;378:2078–92. 10.1056/NEJMoa1801005 - DOI - PubMed
    1. Gandara DR, Li T, Lara PN, et al. . Acquired resistance to targeted therapies against oncogene-driven non–small-cell lung cancer: approach to subtyping progressive disease and clinical implications. Clinical Lung Cancer 2014;15:1–6. 10.1016/j.cllc.2013.10.001 - DOI - PMC - PubMed
    1. Schadendorf D, Hodi FS, Robert C, et al. . Pooled analysis of long-term survival data from phase II and phase III trials of ipilimumab in unresectable or metastatic melanoma. JCO 2015;33:1889–94. 10.1200/JCO.2014.56.2736 - DOI - PMC - PubMed