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Review
. 2023 Nov 21;15(23):5505.
doi: 10.3390/cancers15235505.

Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer

Marco Siringo  1   2 , Javier Baena  1   3 , Helena Bote de Cabo  1   3 , Javier Torres-Jiménez  1   3 , María Zurera  1   3 , Jon Zugazagoitia  1   3   4 , Luis Paz-Ares  1   3   4   5
Affiliations
Review

Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer

Marco Siringo et al. Cancers (Basel). .

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their long-term benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody-drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-be-published phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives.

Keywords: antibody–drug conjugates; immunotherapy combinations; second line NSCLC.

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Conflict of interest statement

M.S.: The authors declare no conflict of interest. J.B.: Honoraria: AstraZeneca; Bristol-Myers Squibb and Pfizer. Consulting or Advisory Role: AstraZeneca; Roche; Access Oncology. Expert Testimony; Roche. Travel, Accommodations, Expenses: MSD; Roche; Janssen Oncology. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. J.T.-J.: The authors declare no conflict of interest. M.Z.: The authors declare no conflict of interest. J.Z.: has served as a consultant for Sanofi, Astra Zeneca, BMS, Roche, Pfizer, Novartis, and Guardant Health. He reports speakers’ honoraria from Sanofi, Takeda, BMS, Pfizer, Roche, Astra Zeneca, NanoString and Guardant Health. He reports travel honoraria from Sanofi, Takeda, BMS, Pfizer, Roche, Astra Zeneca, and NanoString. He has received research support/funds from BMS, Astra Zeneca, and Roche. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. L.P.-A.: Altum sequencing, Other, Personal, Board member Amgen, Advisory Board, Personal AZ, Advisory Board, Personal, Speaker fees Bayer, Advisory Board, Personal Beigene, Advisory Board, Personal, Speaker fees BMS, Advisory Board, Personal, Speaker fees Daichii, Advisory Board, Personal, Speaker fees Genomica, Other, Personal, Board member GSK, Advisory Board, Personal Janssen, Advisory Board, Personal Lilly, Advisory Board, Personal, Speaker fees Medscape, Advisory Board, Personal, Speaker fees Merck Serono, Advisory Board, Personal Mirati, Advisory Board, Personal MSD, Advisory Board, Personal, Speaker fees Novartis, Advisory Board, Personal PER, Advisory Board, Personal, Speaker fees Pfizer, Advisory Board, Personal Pharmamar, Advisory Board, Personal, Speaker fees Roche, Advisory Board, Personal, Speaker fees Sanofi, Advisory Board, Personal Takeda, Advisory Board, Personal Stab Therapeutics, Member of Board of Directors, Personal, Board member AACR, Other, No financial interest, Member AECC, Other, No financial interest, Foundation Board Member Alkermes, Coordinating PI, Institutional, Financial interest Amgen, Coordinating PI, Personal, Financial interest ASCO, Other, No financial interest, Member ASEICA, Other, No financial interest, President ASEICA(Spanish Association of Cancer Research) AstraZeneca, Coordinating PI, Institutional, Financial interest BMS, Coordinating PI, Institutional, Financial interest Daiichi Sankyo, Coordinating PI, Institutional, Financial interest ESMO, Other, No financial interest, Member Janssen-Cilag International NV, Coordinating PI, Institutional, Financial interest Lilly, Coordinating PI, Institutional, Financial interest Merck Sharp & Dohme Corp., Coordinating PI, Institutional, Financial interest Novartis, Coordinating PI, Institutional, Financial interest ONCOSUR, Other, No financial interest, Foundation president Pfizer, Coordinating PI, Institutional, Financial interest PharmaMar, Coordinating PI, Institutional, Financial interest Roche, Coordinating PI, Institutional, Financial interest Sanofi, Coordinating PI, Institutional, Financial interest Small Lung Cancer Group, Other, No financial interest, member Takeda, Coordinating PI, Institutional, Financial interest Tesaro, Coordinating PI, Institutional, Financial interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Therapeutic algorithm for second-line metastatic non-oncogene addicted NSCLC. AA = anti angiogenic agents; ADCs = antibody drugs conjugates; ChT = chemotherapy, IO = immunotherapy; ChT = chemotherapy, irAE = immune-related adverse event; mono= monotherapy; NSCLC = non-small cell lung cancer; PD = progression disease; PFS = progression free survival.
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