Lung Cancer

Pursuing Novel Treatment Approaches in Non-Small Cell Lung Cancer

UNMET NEED

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

CHEMORADIATION THERAPY

ACTIVE SURVEILLANCE PERIOD

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

  • CHEMORADIATION THERAPY
  • ACTIVE SURVEILLANCE PERIOD

 

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

HARNESSING THE IMMUNE SYSTEM

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

UNMET NEED

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.

HARNESSING THE IMMUNE SYSTEM

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.

References

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