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Review
. 2019 Apr 25;12(1):45.
doi: 10.1186/s13045-019-0731-8.

Emerging therapies for non-small cell lung cancer

Chao Zhang  1   2 , Natasha B Leighl  3 , Yi-Long Wu  1 , Wen-Zhao Zhong  4
Affiliations
Review

Emerging therapies for non-small cell lung cancer

Chao Zhang et al. J Hematol Oncol. .

Abstract

Recent advances in the field of novel anticancer agents prolong patients' survival and show a promising future. Tyrosine kinase inhibitors and immunotherapy for lung cancer are the two major areas undergoing rapid development. Although increasing novel anticancer agents were innovated, how to translate and optimize these novel agents into clinical practice remains to be explored. Besides, toxicities and availability of these drugs in specific regions should also be considered during clinical determination. Herein, we summarize emerging agents including tyrosine kinase inhibitors, checkpoint inhibitors, and other potential immunotherapy such as chimeric antigen receptor T cell for non-small cell lung cancer attempting to provide insights and perspectives of the future in anticancer treatment.

Keywords: Bispecific antibodies; CAR-T; Checkpoint inhibitors; Lung cancer; Tyrosine kinase inhibitors.

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The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Reported acquired resistance to osimertinib and corresponding potential strategies. Preclinical and clinical data consisted of EGFR-dependent/independent resistant mechanism to osimertinib were included. Additional corresponding TKI with osimertinib may be available in other oncogene-driven resistance, and whether checkpoint inhibitors would be beneficial in pan-negative patients after osimertinib or treatment failure was yet to be answered. TBP, treatment beyond progression
Fig. 2
Fig. 2
Chord diagrams for sensitive and resistant mutations regarding ALK-TKIs. Both preclinical data and clinical reported cases (preferred) were enrolled to determine the efficacy of ALK-TKIs to different ALK-dependent mutations. Crizotinib had smallest sensitive mutation profiles compared to lorlatinib while opposite in resistant profiles. a Mutation profiles showed responsiveness to different ALK-TKIs. b Mutation profiles reported to be resistant to different ALK-TKIs
Fig. 3
Fig. 3
Results of posted and pending trials of PD-1/PD-L1 inhibitors between lung adenocarcinoma and squamous carcinoma regarding different PD-L1 expression. All posted and pending trials were stratified based on the indication for different expression of PD-L1 and treatment lines. Only PD-1/PD-L1 inhibitors of pembrolizumab, nivolumab, atezolizumab, durvalumab, and avelumab were included except for checkpoint inhibitors from Chinese pharmaceutical companies due to early phase trials of these checkpoint inhibitors for lung cancer. Checkmate-227, although regardless of PD-L1 expression, required high tumor mutation burden (TMB)
Fig. 4
Fig. 4
Perspectives for the evolving modalities of immunotherapy in NSCLC. Treatment modalities involving immunotherapy in NSCLC had evolved from second-line setting to first-line setting. Prior immunotherapy, highly selective patients, and combination strategies had raised significant efficacy improvement but increased toxicities as well. Novel immunotherapy in the future combined with multiple novel biomarkers may infinitely consolidate the clinical role of immunotherapy in advanced NSCLC
See this image and copyright information in PMC

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