Responding to Resistance in Lung Cancer
Sponsored Content by SANOFI
Lung cancer is one of the deadliest forms of cancer, accounting for nearly 1.8 million or 18% of all cancer deaths in 2020,1 which is more than colon, breast and prostate cancers combined.1 In that year alone, there were more than 2.2 million new cases of lung cancer globally.1
When we talk about lung cancers, they are classified as either non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC). NSCLC is the most common form of lung cancer, accounting for about 80-85% of cases.2,3 Within NSCLC, there are three distinct types: adenocarcinoma, which is comprised of clumped cells that look like glands; squamous cell carcinoma, which is comprised of clumped cells that line the respiratory tract inside of the lungs; and large cell carcinoma, which are larger than the other two types and can appear in any part of the lungs.2,3
Sadly, the majority of people diagnosed with NSCLC have advanced disease4 and, although several treatment options have been approved in recent years, there is still an unmet need for new therapies that have the potential to improve outcomes for those living with this difficult-to-treat disease. The estimated five-year overall survival (OS) rate, although improved with the introduction of immunotherapy and other new treatment options, remains stubbornly low.5
HIGH UNMET NEEDS PERSIST IN LUNG CANCER
When we look at treatments, immune checkpoint inhibitors have dramatically altered the therapeutic landscape for advanced NSCLC.6 Immunotherapy with or without platinum-based chemotherapy is currently the standard of care for most people diagnosed with NSCLC.7
Unfortunately, resistance to immunotherapy and chemotherapy poses a significant challenge. Many people with NSCLC treated with immune checkpoint inhibitor monotherapy do not respond to treatment. Those who have advanced NSCLC and initially respond to treatment with immune checkpoint inhibitors develop acquired resistance after a median progression-free survival (PFS) of approximately 10 months.8
People with advanced NSCLC whose disease progresses after first-line treatment with immune checkpoint inhibitors have a poor prognosis with currently available therapies. In addition, guidelines do not recommend retrial of another immunotherapy after failing on first-line treatment with immunotherapy.9 Real-world data shows a median PFS of 2.4-5.5 months, and median OS of 4.6-10.7 months for people with advanced NSCLC who progressed to second-line therapies after failing first-line immunotherapy or immunotherapy in combination with chemotherapy.10
THE IMPORTANCE OF BIOMARKER TESTING
Over the past 15 years, the development of new therapeutic options has been made possible by advancements that have improved our understanding of NSCLC tumor biology. These advancements have helped researchers identify people living with NSCLC most likely to respond to ICI and to identify genetic mutations in NSCLC tumors.11 Additional discoveries have led to the development of therapies that can selectively target these mutations by inhibiting specific molecular factors involved in cancer cell proliferation.12 To identify these mutations, many people living with advanced NSCLC who are eligible for treatment undergo biomarker testing.13 Understanding each person’s unique set of biomarkers through testing may be an important part of informing the approach to their care.
While the pace of research and development in this space has been remarkable, there is a critical need to identify novel biomarkers, particularly for those living with NSCLC who have primary or acquired resistance to currently available treatments. Robust research efforts across the industry are underway to continue to respond to this challenge and identify new biomarkers to help uncover potential therapeutic options for people living with NSCLC, as there is so much left to be learned.
A POTENTIAL NEW TARGET IN LUNG CANCER
At Sanofi, we are committed to modernizing cancer care by discovering, developing and delivering breakthrough therapies. Building on our rich legacy in cancer research and drug development, we have significantly strengthened our commitment to oncology over the past few years and are working tirelessly to research emerging biomarkers and develop novel therapies that may have the potential to transform the treatment of difficult-to-treat cancers.
More specifically, we are exploring a potentially predictive biomarker in NSCLC, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5). Early studies have found that CEACAM5 is highly expressed (≥ 50% of tumor cells with 2+ intensity by immunohistochemistry) in approximately 25% of people diagnosed with advanced non-squamous NSCLC.14 CEACAM5 has higher differential expression in NSCLC tumor tissue compared to healthy lung tissue,15,16,17 which may indicate that CEACAM5 could be a potential target for new treatments in NSCLC by allowing antibodies to selectively deliver cytotoxic drugs to cancer cells while sparing healthy tissue.18,19,20
While we are encouraged by the progress that has been made in NSCLC research, given the complexity of the disease we recognize the need for new therapies that strike a balance between efficacy and tolerability. Our goal is to ease the burden of cancer and improve the quality of life for those living with the disease. We are committed to partnering with healthcare providers to identify opportunities for innovation to advance care for those living with NSCLC.
To learn more about CEACAM5, please visit www.ceacam5.com.