A recent study led by the National Cancer Institute (NCI) showed that lung cancer deaths have dropped steadily since 2001.

 Death rates for the most common form of lung cancer, non-small cell lung cancer (NSCLC),

 fell by about 3% every year from 2001 to 2013.

 The drop in mortality was even more pronounced – about 6% – from 2013-2016.

 The decline was mostly attributed to reduced smoking rates, but NCI researchers suggested that there may be a correlation between increased survival and the use of medicines that target specific genetic alterations in lung cancer cells.

According to the authors, doctors began routinely testing people with metastatic non-small cell lung cancer (NSCLC) in 2013 for the alterations, or mutations, targeted by these drugs. The tests, known as biomarker tests, can help clinicians to determine which treatment options are more likely to be effective against a patient’s specific type of lung cancer.

 The key molecular biomarkers that play a role in metastatic NSCLC – and for which there are matching FDA-approved targeted treatments – are EGFR, ALK, BRAF V600E, ROS1, NTRK, MET and RET.

 Testing for actionable biomarkers has traditionally been done on tissue biopsy samples, although blood tests are now available as an additional option.

Expert guidelines recommend that all patients with metastatic NSCLC get biomarker testing to better identify their specific cancer type.

 For example, people of Asian descent are at a higher risk of developing metastatic NSCLC caused by a mutation in the EGFR gene.

 These mutations present in up to 50% of Asian patients were diagnosed with a common subtype of NSCLC called adenocarcinoma, compared to only 10%-15% of patients in the US and Europe.

 However, only 60% of Asian metastatic NSCLC patients in New York and 57% of patients in Los Angeles – two of the most heavily populated Asian American cities in the United States – are being tested for EGFR mutations.

“Biomarker tests are critical in subsets of the population where we know certain lung cancer mutations like EGFR occur more often, such as in Asian Americans. We must educate these patients about their risk factors and the importance of biomarker testing as part of a complete lung cancer diagnosis,” said Elaine Shum, MD, Perlmutter Cancer Center at NYU Langone Health.

Many Asian Americans may not be aware of their lung cancer risk factors, including the higher prevalence of certain biomarkers, such as EGFR mutations, compared to other racial or ethnic groups. As the number of metastatic NSCLC cases and deaths continue to rise in some Asian American communities,

 a panel of lung cancer experts has identified several factors contributing to the disparity in this population. The panel, sponsored by AstraZeneca as part of the company’s “It's Okay to Ask” educational program, convened in Los Angeles on January 15, 2020 and virtually on October 29, 2020 to discuss this problem. “It's Okay to Ask” is designed to empower lung cancer patients and their caregivers to take a proactive approach to understanding their treatment options.

Despite increased awareness of lung cancer in recent years, stigma and blame remain a challenge for patients. According to the panel, many Asian American lung cancer patients feel guilt or shame for missing work or for being unable to care for themselves and their family. The stigma of lung cancer can contribute to a sense of fatalism in both patients and their doctors – impeding timely and accurate diagnosis and treatment.

Cultural factors impact access to testing and treatment, panel members said. In many Asian communities, patients are socialized to accept information and instructions from their doctor without being actively involved. Patients may be reluctant to share their lung cancer diagnosis with family and friends because they don’t want to be a burden. Some adult children may be hesitant to tell elderly family members about a lung cancer diagnosis to shield them from emotional stress.

“In Asian culture, the stigma of lung cancer may make it more difficult for some patients to fully confront the disease. We must help these patients understand that lung cancer isn’t their fault, and that it’s okay to talk openly about the disease and get help,” said David Park, MD, St. Jude Heritage Health.

Asian Americans who are diagnosed with metastatic NSCLC face real challenges. Biomarker testing as part of a complete diagnosis for metastatic NSCLC patients may be a key to solving some of the racial and ethnic disparities in lung cancer mortality and survival. The panel set forth strategies to increase Asian Americans’ access to testing and treatment along the continuum of care:

 Provide patients and caregivers with culturally and linguistically tailored information, educational tools, awareness campaigns, and doctors who can speak to patients in their native languages

 Confront the stigma of lung cancer with science, educating Asian Americans about their increased risk of having EGFR mutations

 Implement lung cancer biomarker testing in communities with dense Asian American populations with limited healthcare access

Elaine Shum, MD, Perlmutter Cancer Center at NYU Langone Health, New York
David Park, MD, St. Jude Heritage Health, Fullerton, California
Young Kwang Chae, MD, MPH, Feinberg School of Medicine at Northwestern Medicine, Chicago
Songchuan Guo, MD, Icahn School of Medicine at Mount Sinai, New York
Kin Lam, MD, Mount Sinai Beth Israel Medical Center and New York Presbyterian Hospital, New York

Howlader N, Forjaz G, Mooradian MJ, et al. The effect of advances in lung cancer treatment on population mortality. 

American Cancer Society. Key Statistics for Lung Cancer. 

https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html

Cancer.Net. Understanding Targeted Therapy. 2020. 

https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/understanding-targeted-therapy

Dong J, Li B, Lin D, et al. Advances in targeted therapy and immunotherapy for non-small cell lung cancer based on accurate molecular typing. 

Seijo LM, Peled N, Ajona D, et al. Biomarkers in lung cancer screening: achievements, promises and challenges. 

Pennell NA, Arcila ME, Gandara DR, West H. Biomarker Testing for Patients With Advanced Non–Small Cell Lung Cancer: Real-World Issues and Tough Choices. 

Schabath MB, Cress D, Munoz-Antonia T. Racial and ethnic differences in the epidemiology and genomics of lung cancer. 

Li T, Kung HJ, Mack PC, Gandara DR. Genotyping and genomic profiling of non-small cell lung cancer: implications for current and future therapies. 

Midha A, Dearden S, McCormack R. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). 

Diaceutics Data. Testing Rates for Asian Territories. February 2019. Accessed November 25, 2019.

American Cancer Society. Cancer Facts & Figures 2016. Special Section: Cancer in Asian Americans, Native Hawaiians, and Pacific Islanders. Accessed November 25, 2019.

©2020 AstraZeneca. All rights reserved.
US-45758 Last Updated 12/20

Articles

More Can Be Done for Asian American Lung Cancer Patients

For years, there was little progress in the development of new treatments for women with 

-mutated ovarian cancer. As a result, genetic testing at diagnosis was not routinely performed except for patients with a family history of cancer or a young age of onset.

 In the last few years, however, targeted treatments have emerged, expanding treatment options, genetic testing, and tumor testing to a wider group of patients.

These individualized treatments reinforce the importance of knowing the 

 status of all women with ovarian cancer.

 Testing to determine whether a patient has germline and/or somatic 

 mutations is now crucial to physicians in making informed treatment decisions.

, Angeles Alvarez Secord, MD, MHSc, of Duke Cancer Institute, discusses the importance of genetic and tumor testing in ovarian cancer and the potential impact on treatment decisions.*

: Why is tumor testing important in ovarian cancer?

: Tumor testing is used to determine if a patient has somatic mutations. It is crucial because, like germline testing, tumor testing can impact treatment decisions.

 Both germline and somatic mutations have shown response to treatments that specifically target 

-mutated cancer cells such as PARP inhibitors.

What is the difference between germline and somatic mutations?

Germline mutations are inherited and are present in all our cells at birth, while somatic mutations are acquired after birth and are present only in the cancerous tumor. Germline mutations can be passed onto your offspring, while somatic mutations cannot.

 While germline mutations can be identified in tissue, they require confirmation with a blood or saliva test.

 Somatic mutations are detected by testing a tissue sample of the tumor itself (called tumor testing or genomic testing).

 It is possible for a woman to have a somatic mutation in her tumor even if she does not have an inherited (germline) mutation. In turn, if a woman has a germline 

 mutation, that mutation will also be present in her tumor cells.

Who should be tested for germline and somatic genetic mutations and when?

Current guidelines, endorsed by numerous organizations including the National Comprehensive Cancer Network, American Society of Clinical Oncology, Society of Gynecologic Oncology, National Society of Genetic Counselors, and the American Congress of Obstetrics and Gynecology, now recommend genetic testing for all women with ovarian, fallopian tube and primary peritoneal cancer regardless of age or family history.

 It’s important to test at diagnosis so we can identify patients with germline and/or somatic mutations to determine the most appropriate course of treatment.

How have ovarian cancer treatment advances impacted genetic testing?

The results of clinical trials have demonstrated that women with ovarian cancers associated with 

 mutations benefit by adding treatments with PARP inhibitors and have significantly changed the way we approach genetic testing.

 Genetic testing was and still is important to identify if a person or their family member(s) (cascade testing) have a genetic predisposition to cancers so that screening and preventive measures could be used.

 But now, with the emergence of targeted treatments such as PARP inhibitors, which target cancers that rely on the PARP enzyme to repair damaged DNA,

 it becomes essential to determine a patient's 

status at the very beginning of their diagnosis for treatment purposes.

 status helps us determine which patients should receive PARP inhibitor maintenance therapy after front-line chemotherapy and assist in treatment planning for those with recurrent disease.

status provides important prognostic, preventive, and therapeutic information.

What advances have there been in genetic testing?

We’ve seen genetic testing improve since 2014. Newer tests can find mutations that may have been previously missed by older tests. Thus, ovarian cancer survivors who had a negative or indeterminate genetic test before 2014 should speak with a genetic counselor or their doctor to see if additional testing is right for them.

*Dr. Alvarez Secord was not compensated for her participation in this article.

Ruddy KJ, Risendal BC, Garber JE, Partridge AH. Cancer Survivorship Care: An Opportunity to Revisit Cancer Genetics. 

Evans T, Matulonis U. PARP Inhibitors in Ovarian Cancer: evidence, experience and clinical potential. 

Hennessey BT, Timms KM, Carey MS, et al. Somatic Mutations in 

 Could Expand the Number of Patients That Benefit from Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer. 

National Cancer Institute. BRCA Mutations: Cancer Risk and Genetic Testing. 

Koczkowska M, Zuk M, Gorczynski A, et al. Detection of somatic 

 mutations in ovarian cancer — next-generation sequencing analysis of 100 cases. 

American Cancer Society. Changes in Genes. 

Frey MK, Pothuri B. Homologous recombination deficiency (HRD) testing in ovarian cancer clinical practice: a review of the literature. 

National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. 2019. 

Society of Gynecologic Oncology. SGO Clinical Practice Statement: Genetic Testing for Ovarian Cancer. 2014. 

Lu KH, Wood ME, Daniels M, et al. American Society of Clinical Oncology Expert Statement: Collection and Use of a Cancer Family History for Oncology Providers. 

Vergote I, Banerjee S, Gerdes AM, et al. Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients. 

 Mutation in Ovarian Cancer: Testing, Implications and Treatment Considerations. 

National Cancer Institute. NCI Dictionary of Cancer Terms/PARP Inhibitor. 

Women who have not been diagnosed with ovarian cancer but are concerned about their risk for developing the disease should, most importantly, know their family history. They should also speak to their doctor or genetic counselor about whether genetic testing for inherited 

Angeles Alvarez Secord, MD, MHSc, discusses the importance of genetic testing and tumor testing in ovarian cancer and the potential impact on treatment decisions.

The Importance of Genetic Testing in Ovarian Cancer: Diagnosis and Treatment

Advancing cancer care requires more than just science. It’s a collective effort driven by passionate individuals and organizations dedicated to making a difference for those living with and affected by cancer. For patients and their families, that community of healthcare professionals, researchers, caregivers, advocates, policymakers, educators and others who offer relief in extraordinarily difficult times are cause for celebration.

Celebrating the Difference Makers in Oncology Care

 Cancer, a new effort to spotlight the countless individuals and organizations at the forefront of cancer care. The program looks to amplify the research, advocacy, policy, best practices, support initiatives and all of the important work aiming to one day eliminate cancer as a cause of death.

 (Cancer Community) Awards recognize contributions made in four categories: extending quality care to underserved communities, improving the patient experience, advancing precision medicine or just doing something flat-out inspiring to improve oncology care.

 Awards recognize the unsung heroes of oncology — whether it be individual researchers, doctors, nurses, pharmacists, patients, advocates or entire organizations – who are sometimes overlooked by traditional award programs and who work at the grassroots level to impact people living with cancer and their families.

 Award, selected by a broad group of experts drawn from the community, will receive $50,000 that they can pay forward by donating to a non-profit organization that serves the cancer community. They will also be honored at a ceremony in New York City and have their work featured in a variety of media opportunities. Above all, the importance of paying it forward and spotlighting all those in the community exemplifies the spirit of Y

 Cancer to ultimately change cancer from one person’s journey into a true community effort.

Join the movement to spotlight the difference makers and share a story of an individual or organization in the oncology community who has inspired you by visiting: 

Advancing cancer care requires more than just science. It’s a collective effort driven by passionate individuals and organizations dedicated to making a difference for those living with and affected by cancer.

YOUR Cancer Movement Spotlights Oncology HCPs and Community

Despite major discoveries in research, lung cancer remains the leading cause of cancer death in the United States among men and women, accounting for about one-quarter of all cancer deaths — more than breast, prostate and colorectal cancers combined.

 Only 16% of patients are diagnosed in the early stages, when the tumor is still localized to the lung.

 For patients diagnosed at a later stage, when their cancer has spread to other organs, the prognosis is especially poor.

 For this reason, more advanced treatments are acutely needed for patients diagnosed with advanced stage lung cancer.

AstraZeneca, which has designated Oncology as one of its 5 growth platforms, has a robust lung cancer research program to help address the significant unmet needs for treatments at every stage of the disease. The company recently received its sixth Breakthrough Therapy Designation from the US Food and Drug Administration for an oncology medicine since 2014, including 2 in the past 8 months based on clinical trial data exploring non—small cell lung cancer (NSCLC) therapies.

Andrew Coop, vice president, US Medical Affairs, Oncology, at AstraZeneca, recently spoke with 

 about the company’s ambition to address the significant unmet need for treatments at every stage of the lung cancer continuum and the rapid progress in NSCLC, which represents 80% to 85% of all types of lung cancer.

 What is your company’s approach to lung cancer?

 At AstraZeneca, we are committed to developing therapies to help patients with lung cancer across all stages of disease. We have a portfolio of approved medicines and investigational compounds to both target genetic changes in tumor cells and stimulate the body’s immune system to attack tumors.

Lung cancer is not one disease. Discoveries of biomarkers like PD-L1 and mutations like 

, have transformed the lung cancer treatment paradigm to help physicians better treat patients through immunotherapies and targeted therapies. Our approach is focused on using ground-breaking science to further understand lung cancer by identifying biomarkers that provide actionable targets for the development of precision medicines. We believe personalized treatment approaches ensure the potential for best patient outcomes.

 our work has been driven by identifying mechanisms through which tumor cells grow and proliferate, so we can develop drugs that target these mutations and pathways. Since then, our research and development teams have accelerated the understanding of key molecular mutations in lung cancer, and the use of specific mutations as biomarkers has enabled us to develop precision therapies being investigated for specific subgroups of lung cancer patients with significant unmet needs.

You mentioned a transformation of the lung cancer treatment paradigm. How are you seeing this play out in practice? 

Targeted and Immuno-Oncology (IO) therapies are now helping specific subgroups of lung cancer patients in treatment settings where options have traditionally been limited. Integral to ensuring that the right patients receive the right treatment at the right time is the development of companion diagnostics. Quality of testing is paramount to optimal decision making.

At various points in treatment, some patients today have options that they would not have had decades ago, which is why testing for genetic mutations and predictive biomarkers, for example, is more important than ever to facilitate treatment option discussions regardless of the line of therapy. Most patients diagnosed with metastatic NSCLC should undergo biomarker testing both at diagnosis and at progression.

Has the change in the lung cancer treatment paradigm affected your development process?

Absolutely. Alongside research in new medicines, AstraZeneca is collaborating to deliver a range of diagnostic technologies to assess disease at all stages and ensure development of optimally targeted therapies. We partnered to launch the first tissue-based diagnostic and the first plasma-based (ctDNA) diagnostic to identify 

 mutations in NSCLC, both of which are used extensively in clinical practice, and we are developing assays to identify patients who may be eligible for treatment with our IO medicines. We are also focused on ensuring better understanding of and confidence in assays already in market through our practice-changing concordance research.

And that is a major focus of your Immuno-Oncology pipeline, right? How is that changing the status quo? 

As we're continuing to advance science for NSCLC patients with identifiable driver mutations, we are simultaneously pushing towards a new era with our IO pipeline.

For many years, patients with certain stages of NSCLC without actionable mutations—particularly those whose tumors were inoperable&mdash;were often treated with chemotherapy and/or radiation therapy — but today, treatment is changing to include IO. This is the result of large, Phase 3 studies that have indicated that certain IO medicines can delay disease progression for specific types of NSCLC.

 That said, different IO treatments have different results, even in the same types of disease — so it’s important to select treatments based on where data shows them to be effective.

One setting where additional options are needed is the locally advanced stage of disease: approximately one in four patients with NSCLC present with Stage III disease, and a majority of these patients are determined to have unresectable tumors. Chemoradiation therapy (CRT) is often the standard of care followed by active surveillance — a “watch and wait” period that can be stressful for patients. To date, the recommendation in this setting has been a period of active surveillance, as there has been limited advancement in this setting over the last 10 years, despite the reality that up to 89% of patients will progress to metastatic disease following CRT.

So, is AstraZeneca primarily pursuing only an IO strategy?

At AstraZeneca, IO is something we are passionate about, but we are harnessing the power of four scientific platforms — Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – as well as championing the development of personalized combinations. And we won’t settle and say, “good enough,” even when a therapy has been developed.

For example, we know that targeted therapies work well for patients, but we also know that a new generation of TKIs is needed in the metastatic EGFR setting and we’re leading the way in this area. Treating advanced lung cancer that has metastasized can be challenging. Targeted therapies, like EGFR inhibitors, eventually stop working for most people, usually because the cancer cells develop other resistance mechanisms like another mutation in the 

 gene. We are working on improving the outcomes of initial therapies, as well as research in resistance mechanisms. Other areas of research with a very high unmet medical need are central nervous system metastases in NSCLC patients.

In the future, as new treatment approaches and classes of therapy emerge, the goal remains clear: to one day eliminate lung cancer as a cause of death. Our unrelenting pursuit of science aims to deliver more breakthrough therapies with the goal of extending and improving the lives of patients across all stages of disease and lines of therapy.

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2018. 

Shepherd FA, et al. Lung cancer in 2013: state of the art therapy for metastatic disease

American Lung Association: Lung cancer fact sheet. Available at: 

http://www.lung.org/lung-disease/lung-cancer/resources/facts-figures/lung-cancer-fact-sheet.html

Hendler FJ, Ozanne BW. Human squamous cell lung cancers express increased epidermal growth factor receptors. 

Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. 2017. 

Herzberg B, Campo MJ, Gainor JF. Immune checkpoint inhibitors in non-small cell lung cancer. 

Our research is also guided by our commitment to transforming outcomes for patients with lung cancer whose treatment options are limited. We believe that being a leader in lung cancer means following the science, exploring treatments beyond metastatic disease, as well as improving current standards of care.

While there are efforts underway to address the significant unmet need for treatments at every stage of the lung cancer continuum, there has been rapid progress in NSCLC.

Non-Small Cell Lung Cancer: What's on the Horizon?

Immuno-oncology is currently among the most discussed topics in cancer research, and anti-PD-L1/PD-1 antibodies are driving the conversation as some of the most unique anti-cancer therapeutic approaches. But many remain unaware of the science behind this class of treatments that could bring hope to patients facing deadly cancers.

PD-L1 (programmed cell death ligand-1) helps cancerous tumors evade detection by the immune system through binding to the PD-1 receptor on cytotoxic T lymphocytes, also known as T cells. When this happens, T cells are unable to identify and attack cancerous cells, giving the cancer an opportunity to spread. Researchers have identified the so-called pathway between PD-L1 and PD-1 as a target for a new generation of cancer therapies: by disabling interaction between PD-L1 and PD-1, the T cells retain their ability to identify and attack cancerous cells, contributing to the ability of the immune system to fight cancer.

With this evolving understanding of how cancer avoids detection, researchers have several types of approaches to re-enable the immune system, involving different pathways. Two of these pathways are anti-PD-1 antibodies, which interfere with the PD-1 receptor on the immune system’s T cells, and anti-PD-L1 antibodies, which interfere with the PD-L1 receptors. Antibodies inhibiting the PD-1/PD-L1 pathway have shown encouraging antitumor activity across multiple tumor types, such as specific types of bladder cancer, head and neck squamous cell carcinoma, non-small cell lung cancer, pancreatic cancer, liver cancer, renal cell carcinoma, and melanoma. 

Clinical studies conducted and ongoing by multiple investigators also suggest the potential for improving treatment efficacy by using a variety of combination approaches, including immunotherapeutic agents that target different pathways, such as PD-L1 and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). Since PD-L1 and CTLA-4 regulate immune responses by different mechanisms, investigations targeting both checkpoints provide the potential to enhance the effects.

“Each day, our scientists are gaining a more thorough understanding of what drives cancers: how they spread and avoid detection by the immune system,” said Andrew Coop, Vice President, Medical Affairs, Oncology at AstraZeneca US. “We are at the precipice of potential new treatment paradigms — with the potential to make a meaningful difference for patients who have limited options. At AstraZeneca, we are more driven than ever to bring new immuno-oncology options to patients facing devastating diagnoses.”

Research is underway to explore this important new class of therapies, and that research is rapidly evolving. For more information, 

Immuno-oncology is among the most discussed topics in cancer research, but many are unaware of the science behind this class of treatments. Learn how it works.

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Articles

More Can Be Done for Asian American Lung Cancer Patients

The Importance of Genetic Testing in Ovarian Cancer: Diagnosis and Treatment

YOUR Cancer Movement Spotlights Oncology HCPs and Community

Non-Small Cell Lung Cancer: What's on the Horizon?

Sponsored Content: The Changing Paradigm of Cancer Research