Lung Cancer

Pursuing Novel Treatment Approaches in Non-Small Cell Lung Cancer


The majority of lung cancers are NSCLC2

An estimated 190,000 patients will be diagnosed with NSCLC in the United States in 20171,2

Approximately 1 in 4 NSCLC patients present with locally advanced disease in the US3-8


Over 43,000 patients were diagnosed with locally advanced NSCLC in the US in 20153

Learn more about the prevalence and current treatment outcomes in locally advanced NSCLC

Learn more about the prevalence and current treatment outcomes in locally advanced NSCLC

Current treatment recommendations for locally advanced NSCLC

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend concurrent chemoradiation therapy (CRT) for locally advanced, unresectable tumors (Stage IIIB T1-3, N3). After 6 to 7 weeks of CRT, patients are monitored* to determine if disease has progressed.9



67% of patients with locally advanced NSCLC responded to CRT in one study10



67% of patients with locally advanced NSCLC responded to CRT in one study10

*Patients receive physicals and CT scans—with or without contrast—every 3 to 6 months for 3 years, then every 6 months for 2 years, then physicals and a low-dose CT scan without contrast annually.9

More than half of patients with NSCLC experience distress associated with waiting for the results of imaging scans during the active surveillance period.11,12

The standard of care has not advanced for more than 10 years13

Since there are no FDA-approved therapies following CRT, it is a period of active surveillance as opposed to active treatment.9

There is a significant need for improved outcomes after CRT

Up to 89% of patients progress to metastatic disease14


  • The median progression-free survival is less than 12 months after the completion of CRT14
  • Median overall survival (OS) after CRT is 22.2 months14

Despite efforts to improve current treatment strategies, survival rates have plateaued13

Consolidation chemotherapy following CRT has not resulted in improved survival times compared with concurrent CRT alone.13

Overall survival across 3 years of current strategies in locally advanced NSCLC. Current strategies only offer 3-year survival rates of 15%-25%

Further manipulations of existing chemotherapy agents are unlikely to provide substantial survival gains. The path forward will require new approaches.13


The role of immunotherapy in treating locally advanced NSCLC

Radiotherapy induces multiple immunomodulatory changes among cancer cells and the tumor microenvironment, such as increased antigen release and upregulation of immunogenic cell surface markers, which may influence the effectiveness of immunotherapy.15,16

Several immune-based approaches are being explored17

Therapeutic vaccines

Antigens introduced into the body resulting in an immune response, activating cytotoxic T cells or inducing antibody production

Adoptive cell therapy (eg, CAR-T)

Selecting and engineering T cells for high tumor specificity ex-vivo, then reintroduced into the patient

Immune checkpoint inhibitors

Target key immune checkpoints to harness the innate immune response to eliminate tumor cells

Immune checkpoint blockade focuses on optimizing T-cell function to stimulate an immune response to cancer.17-20

Exploring new possibilities for patients with locally advanced NSCLC

AstraZeneca is investigating the potential for immunotherapy in this important therapeutic setting. With several clinical trials in lung cancer underway, improved patient outcomes after CRT may soon become a new reality.21

REVIEW immuno-oncology clinical trials for lung cancer


A majority of NSCLC patients are diagnosed as metastatic (Stage IV)

An estimated 190,000 patients in the United States will be diagnosed with NSCLC in 20171-2

57% of patients with NSCLC were diagnosed as metastatic from 2007 to 201322

The 5-year survival rate for metastatic NSCLC is less than 5%22

New first-line therapy options are needed to address specific patient types

A limited percentage of patients have driver mutations or PD-L1 expression ≥50% that open the option for targeted agents or immunotherapy.23,24

≈15% of NSCLC23

EGFR mutations

≈6% of NSCLC23

ALK/ROS1 rearrangements

≈25% of NSCLC24

PD-L1 expression ≥50%

For the majority of patients, there has been limited progress in the standard of care where chemotherapy is the only option.9

Outcomes for patients with advanced NSCLC remain poor

For patients with metastatic NSCLC treated with doublet chemotherapy, different studies have shown that overall survival (OS) is low:

*Doublet chemotherapy regimens include gemcitabine + carboplatin, gemcitabine + paclitaxel, paclitaxel + carboplatin.


NSCLC has the second highest mutational burden among tumor types28

A high tumor mutational burden may be associated with increased sensitivity to immune-mediated treatment approaches, which can establish immunotherapy as a new paradigm for improving outcomes in this patient population.29

Several immune-based approaches are being explored17

Therapeutic vaccines

Antigens introduced into the body resulting in an immune response, activating cytotoxic T cells or inducing antibody production

Adoptive cell therapy (eg, CAR-T)

Selecting and engineering T cells for high tumor specificity ex vivo, then reintroduced into the patient

Immune checkpoint inhibitors

Targets key immune checkpoints to harness the innate immune response to eliminate tumor cells

Blocking immune-inhibitory pathways offers the possibility of durable response

Disrupting multiple, non-redundant immune pathways such as CTLA-4 and PD-L1 may offer synergistic antitumor effects. Complementary inhibition enhances T-cell activation, proliferation, and differentiation into memory T cells. The formation of memory T cells may promote durable antitumor responses.19,30,31

The potential of combination immunotherapy in lung cancer

Combination immunotherapy with dual immune checkpoint blockade is being investigated in a wide range of patient types. AstraZeneca continues to apply emerging scientific research towards the treatment of metastatic NSCLC, for which combination immunotherapy has the potential to broaden the population of those who may benefit.19,30-32

Review a disease education supplement on immunotherapy

Review a disease education supplement on immunotherapy

NCCN=National Comprehensive Cancer Network; CAR-T=chimeric antigen receptor T cell; PD-L1=programmed cell death ligand-1; EGFR=estimated glomerular filtration rate; ALK=anaplastic lymphoma kinase; ROS1=c-ros oncogene 1; VEGF=vascular endothelial growth factor; CTLA-4=cytotoxic T-lymphocyte–associated antigen.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.


1. American Cancer Society. Key statistics for lung cancer. Accessed June 26, 2017. 2. American Cancer Society. What is non-small cell lung cancer? Accessed June 26, 2017. 3. EpiCast Report: Non-Small Cell Lung Cancer (NSCLC)—Epidemiology Forecast to 2025. London, England: GlobalData; November 2016. 4. Aupérin A, Le Pechoux C, Rolland E, et al. Metaanalysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol. 2010;28(13):2181-2190. 5. Johnson DH. Locally advanced, unresectable non-small cell lung cancer: new treatment strategies. Chest. 2000;117(4 suppl 1):123S-126S. 6. Provencio M, Isla D, Sánchez A, Cantos B. Inoperable stage II non-small cell lung cancer: current treatment and role of vinorelbine. J Thorac Dis. 2011;3(3):197-204. 7. Scorsetti M, Navarria P, Mancosu P, et al. Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcomes results with rapid arc. Radiat Oncol. 2010;5:94-102. 8. Fournel P, Robinet G, Tomas P, et al; Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Français de Pneumo-Cancérologie. Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small cell lung cancer: Groupe Lyon-Saint-Etienne d’Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPS 95-01 Study. J Clin Oncol. 2005;23(25):5910-5917. 9. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer v.8.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed June 26, 2017. To view the most recent and complete version of the guidelines, go online to 10. Gandara DR, Chansky K, Albian KS, et al. Long-term survival with concurrent chemoradiation therapy followed by consolidation docetaxel in stage IIIB non-small-cell lung cancer: a phase II Southwest Oncology Group Study (S9504). Clin Lung Cancer. 2006;8(2):116-121. 11. van den Bergh KAM, Essink-Bot ML, Bunge EM, et al. Impact of computed tomography screening for lung cancer on participants in a randomized controlled trial (NELSON trial). Cancer. 2008;113:396-404. 12. Bauml JM, Troxel A, Epperson CN, et al. Scan-associated distress in lung cancer: quantifying the impact of “scanxiety.” Lung Cancer. 2016;100:110-113. 13. Hanna N. Current standards and clinical trials in systemic therapy for stage III lung cancer: what is new? In: 2015 ASCO Educational Book. Alexandria, VA: American Society of Clinical Oncology; 2015. 14. Albain KS, Swann RS, Rusch VW, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small cell lung cancer. Lancet. 2009;374(9687):379-386. 15. Deng L, Liang H, Burnette B, et al. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124(2):687-695. 16. Sharabi AB, Lim M, DeWeese TL, Drake CG. Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol. 2015;16(13):e498-e509. 17. Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 2016;14:73. 18. Madureira P, de Mello RA, de Vasconcelos A, Zhang Y. Immunotherapy for lung cancer: for whom the bell tolls? Tumor Biol. 2015;36(3):1411-1422. 19. Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25-39. 20. Adachi K, Tamada K. Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy. Cancer Science. 2015;106(8):945-950. 21. AstraZeneca. Clinical trials appendix Q1 2017 results update. Accessed July 7, 2017. 22. National Cancer Institute. Cancer stat facts: lung and bronchus cancer. Accessed June 26, 2017. 23. Korpanty GJ, Graham DM, Vincent MD, Leighl NB. Biomarkers that currently affect clinical practice in lung cancer: EGFR, ALK, MET, ROS-1, and KRAS. Front Oncol. 2014;4: 204. 24. Sorensen S. F. et al. PD-L1 Expression and Survival among Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy. Transl Oncol. 9, 64–69 (2016). 25. Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, et al. A randomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol. 2010;21(3):540–547. 26. Treat J, Scogliotti GV, Peng G, et al. Comparison of pemetrexed plus cisplatin with other first-line doublets in advanced non-small cell lung cancer (NSCLC): a combined analysis of three phase 3 trials. Lung Cancer. 2012:76(2):222-227. 27. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355(24):2542-2550. 28. Rajasagi M, Shukla SA, Fritsch EF, et al. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood. 2014;124(3):453-462. 29. Rizvi N, Hellman M, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science. 2015;348(6230):124-128. 30. Das R, Verma R, Sznol M, et al. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015;194(3):950-959. 31. Drake C.G. Combination immunotherapy approaches. Ann Oncol. 2012;23(suppl 8):viii41-viii46. 32. Melero I, Berman DM, Aznar MA, Korman AJ, Pérez Gracia JL, Haanen J. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer. 2015;15(8):457-472.