Special Series: Thoracic Oncology: Current and Future Therapy
First-Line Immunotherapy for Non–Small-Cell Lung Cancer
2Department of Medical Oncology, Centro Integral Oncológico Clara Campal (HM-CIOCC), Hospital HM Delfos, HM Hospitales, Barcelona, Spain
3Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
For patients with metastatic non–small-cell lung cancer (mNSCLC), the last decade has been characterized by critical progress that has contributed to substantially improved survival. In particular, the development of specific antibodies against the programmed death (PD-1) receptor, programmed death-ligand 1 (PD-L1), and the cytotoxic T-lymphocyte–associated protein 4 receptor in the therapeutic strategy of mNSCLC either in first- or in second-line settings have led to unprecedented prolonged survival for a proportion of these patients. Although clinical development of immune checkpoint inhibitors with anti–PD-1 and PD-L1 therapies largely began as monotherapy in the second-line setting, the more recent progress has shifted toward combination approaches in first-line settings as well as the integration of immunotherapy into the clinical paradigm in earlier stages. Today, with the exception of mNSCLC harboring targetable oncogenes, nearly all patients with mNSCLC receive PD-1 or PD-L1 therapy in first-line settings. Here we report the current status of first-line immunotherapy in mNSCLC together with current challenges in selecting the best immunotherapeutic approach for the individual patient.
The implementation of immunotherapies with checkpoint inhibitors has substantially improved therapeutic outcomes of patients with advanced or metastatic non–small-cell lung cancer (NSCLC). In the recent years, different monotherapies as well as different combinations have been reported and approved, which require a clinical interpretation and patient-related assignment.
A current overview on the different treatment opportunities based on the most recent treatment trial reports provides insights into the complex and evolving field of first-line immunotherapies in nononcogenic addicted metastatic NSCLC. Additional results of translational biomarker analyses and clinical considerations of relevant treatment decisions support the transition from clinical trial outcomes to daily practice reality. A concluding outlook on ongoing research and trial concepts offers a view on the promising perspective of immunotherapy in NSCLC.
This overview might help the clinical oncologist in the treatment decision and selection of the most appropriate immunotherapy or immunotherapy combination for his patients with metastatic NSCLC.
Conception and design: Martin Reck, Jordi Remon, Matthew D. Hellmann
Collection and assembly of data: All authors
Data analysis and interpretation: Jordi Remon, Matthew D. Hellmann
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Consulting or Advisory Role: Lilly, MSD Oncology, Merck Serono, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, Roche/Genentech, AbbVie, Amgen, Mirati Therapeutics, Samsung Bioepis, Sanofi/Regeneron
Speakers' Bureau: Roche/Genentech, Lilly, MSD Oncology, Merck Serono, Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Celgene, Pfizer, Novartis, Amgen, Mirati Therapeutics, Sanofi/Aventis
Consulting or Advisory Role: Pfizer, Bristol Myers Squibb, Boehringer Ingelheim, MSD Oncology, AstraZeneca, OSE Immunotherapeutics
Travel, Accommodations, Expenses: Roche/Genentech, Inivata, OSE Immunotherapeutics, AstraZeneca
Matthew D. Hellmann
Stock and Other Ownership Interests: Shattuck Labs, Immunai, Arcus Biosciences, Shattuck Labs, Factorial
Consulting or Advisory Role: Bristol Myers Squibb, Merck, Genentech, AstraZeneca/MedImmune, Mirati Therapeutics, Immunai, Blueprint Medicines, Natera, Shattuck Labs, Arcus Biosciences, Achilles Therapeutics, Adagene, Adicet Bio, Lilly, Janssen, Instil Bio, Mana Therapeutics, PACT Pharma, Regeneron
Research Funding: Bristol Myers Squibb
Patents, Royalties, Other Intellectual Property: A patent has been filed by Memorial Sloan Kettering (PCT/US2015/062208) for the use of tumor mutation burden for prediction of immunotherapy efficacy, and which is licensed to Personal Genome Diagnostics
No other potential conflicts of interest were reported.