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Unmet Clinical Need in the Management of Locally Advanced Unresectable Lung Cancer: Treatment Strategies to Improve Patient Outcomes

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Abstract

Stage III locally advanced non-small cell lung cancer (LA NSCLC) comprises the most heterogeneous group of patients, accounts for one-third of patients with lung cancer, and is unresectable at presentation. Multiple treatment approaches have evolved over the past few decades focusing on timing of chemoradiation (concurrent vs. sequential) and sequencing of therapy (induction vs. consolidation). Concurrent chemoradiation (CCRT) emerged as the standard of care for the majority of the patients worldwide. Despite improvements in median and overall survival (OS) using the concurrent approach, the rate of distant failure remains high. Consolidation with chemotherapy or targeted agents, adding more radiation dose, or induction chemotherapy did not improve OS. With continued research on defining optimal radiation doses and schedules and integrating novel systemic agents, immunotherapy consolidation has renewed optimism. Synergistic use of radiation and immunotherapy can prevent micrometastatic disease and reduce local failure and may have an abscopal effect in addition to survival benefits. The PACIFIC study reported an absolute progression-free survival benefit of 11.2 months with durvalumab consolidation after standard CCRT compared with placebo. The OS data with durvalumab consolidation are encouraging. Durvalumab is the only approved immunotherapy for unresectable stage III LA NSCLC. Improved survival confirms the definitive role of durvalumab as an effective adjuvant therapy after CCRT with no new safety signals. However, the potential mechanisms driving interaction between immunotherapy and chemoradiotherapy require definitive investigation. These mechanisms may help define the timing of immunotherapy initiation as neoadjuvant, adjuvant, or consolidation and maintenance therapy after progression.

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AstraZeneca Pharma India Limited.

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Fig. 1

Reproduced with permission from Detterbeck F.C, Boffa D.J, Kim A.W, et al. The Eighth Edition Lung Cancer Stage Classification. CHEST. 2017; 151: 193–203 [4]

Fig. 2
Fig. 3

Modified with permission from Faien. I, Cummings. A.L, Crosetti A.M, et al. Durvalumab: an investigational anti-PD-L1 monoclonal antibody for the treatment of urothelial carcinoma. Drug Des Devel Ther. 2018; 12: 209–215 [52]

Fig. 4

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Acknowledgements

Funding

The preparation of this article and funding of the journal’s article processing charges were supported by AstraZeneca Pharma India Limited. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis.

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The authors thank AstraZeneca Pharma India Ltd and Chinmayee Joshi from Sciformix Technologies Private Limited, Mumbai for providing medical writing assistance in the development of this manuscript.

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All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

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Senthil Rajappa, Sanjiv Sharma, and Krishna Prasad declare that they have no conflict of interest.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. Basavatarakam Indo-American Cancer Hospital and Research Institute, Hyderabad, India

    Senthil Rajappa

  2. Manipal Hospitals, Bengaluru, India

    Sanjiv Sharma

  3. Mangalore Institute of Oncology, Mangalore, India

    Krishna Prasad

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Rajappa, S., Sharma, S. & Prasad, K. Unmet Clinical Need in the Management of Locally Advanced Unresectable Lung Cancer: Treatment Strategies to Improve Patient Outcomes. Adv Ther 36, 563–578 (2019). https://doi.org/10.1007/s12325-019-0876-4

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