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AstraZeneca showcased its lung cancer leadership at the World Conference on Lung Cancer (WCLC 2023).

At the conference, the highlight session was the Plenary-Presidential Symposium, which featured over 40 abstracts, including FLAURA2, which demonstrated the synergy of Tagrisso (ingredient: osimertinib) with combination chemotherapy.

AstraZeneca's presentation demonstrated a strong case for its ambitious goal of providing treatment to more than half of the world's lung cancer patients by 2030.

To further its commitment to fighting lung cancer, AstraZeneca is partnering with the Lung Ambition Alliance to help lead global efforts to improve early diagnosis, access to treatment, and ultimately reduce lung cancer deaths.

Newsmp had the opportunity to meet with Sunil Verma, MD, the Global Head of Oncology, Medical, at AstraZeneca, at the WCLC 2023. Dr. Verma's team developed Iressa (ingredient: gefitinib), which was the first FDA-approved targeted therapy for lung cancer and led to a paradigm shift in the treatment of lung cancer and other solid tumors.

 

 

◇ Leading lung cancer treatment with Iressa-Tagrisso heritage
Back in 2003, AstraZeneca spearheaded a paradigm shift in the treatment of lung cancer, previously regarded as one of the most difficult cancers to treat, by securing FDA approval for Iressa, the first targeted therapy in the solid tumor field.

Iressa's approval paved the way for the emergence of numerous targeted therapies in various cancer types over the past 20 years, resulting in prolonged survival for cancer patients.

In particular, life expectancy for lung cancer, which was difficult to exceed 1 year, is now exceeding 3 years with the development of the 1st generation targeted therapy Iressa and the 3rd generation Tagrisso.

"AstraZeneca has shared many of its achievements at the WCLC 2023, including more than 40 abstracts, and it was the result of years of research and development," said Dr. Verma. "We developed the first EGFR-TKI, Iressa, in the early 2000s, which allowed us to understand the importance of EGFR mutations itself."

"The IPASS study, published in 2009, not only proved that Iressa was a very important drug for patients, but also laid the foundation for AstraZeneca to make an important milestone in the field of targeted therapy," he added.

"A few years later, we developed a new drug called Tagrisso, a third-generation TKI," he stated. "At the time, it was very important to develop a drug that was more effective than Iressa, that could overcome resistance, and was well-tolerated by patients. In fact, through the research results published in 2018 and 2019, we were able to release Tagrisso, which was one step further developed than Iressa."

"Through this journey, AstraZeneca has gained the confidence and responsibility to develop innovative therapies for lung cancer through science and research, and to lead the treatment of lung cancer," he said. Currently, more than 5,000 lung cancer patients worldwide are participating in our company's lung cancer-related clinical trials (as of 2021)."

Currently, there are more than 15 ongoing global phase 3 clinical trials in the field of lung cancer. "We are confident that we will continue to be a leader in the field of lung cancer treatment, based on our legacy of developing innovative therapies for patients around the world," said Dr. Verma.

 

◇ Innovation in Lung Cancer Survival Through Early Combination of TKI, IO, and ADC
AstraZeneca presented over 40 abstracts during this academic conference, covering a wide range of topics with a variety of treatments at different stages of development.

They introduced treatments for both small cell lung cancer and non-small cell lung cancer, with a focus on targeting the many genetic mutations that occur in non-small cell lung cancer.

AstraZeneca provided a variety of treatment options for lung cancer, including second-generation targeted therapies, third-generation immune therapies, and the next-generation antibody-drug conjugates (ADCs).

Moreover, they aimed to explore the best treatment options by encompassing each therapy along with surgery, and anticancer radiation, striving not only to lead in lung cancer treatment but also to eliminate cancer-related deaths.

“AstraZeneca’s various cancer research strategies are based on important ambitions,” he said. “The first of these ambitions is to eradicate cancer-related deaths, which begins with the development of treatments that can improve patients' survival periods and ultimately achieve a cure.”

"From a treatment perspective, our current research can be categorized into four major domains. The first is targeted therapies like Tagrisso, the second is ADCs, and the third involves immune checkpoint inhibitors, where AstraZeneca is shaping the next wave in immunotherapy," he explained. "Lastly, the fourth area involves studying how to implement effective combination therapy strategies using these treatments."

"The second key strategy in cancer research is to explore how these groundbreaking anticancer agents can be utilized from the early stages," he continued." "This effort encompasses cooperation with various healthcare systems to facilitate early patient diagnosis and the development of multiple diagnostic tools to enable patients to receive more tailored and effective treatments."

"This is the new paradigm that AstraZeneca is trying to create. In other words, it involves developing innovative therapies that improve survival periods, expanding their early use, diagnosing cancer early, and providing personalized precision medicine,” he said. “Through this, we aspire to achieve a vision where AstraZeneca's innovative treatments are delivered to more than half of lung cancer patients, and we are already on our way towards our goal."

 

 

◇ Lung cancer death-free with early detection and early treatment
Lung cancer has been the focus of oncology research in the 21st century, and there have been significant advances in improving survival rates. However, lung cancer still remains the leading cancer incidence and leading cause of cancer death worldwide.

Nevertheless, AstraZeneca has expressed its ambitious vision of a world where no one dies from lung cancer.

AstraZeneca believes that improving early detection rates and early access to innovative therapies can help to reduce lung cancer deaths.

In pursuit of this objective, they hold a range of novel drug candidates in the field of lung cancer and collaborate with experts in lung cancer from around the world, stressing the importance of early diagnosis and working towards its integration into policies across various nations.

"The treatment for lung cancer patients is changing very rapidly," said Dr. Verma. "Still, 60-70% of lung cancer patients are diagnosed in advanced stages, making a cure virtually impossible, which poses limitations in lung cancer treatment."

"Early diagnosis of patients is crucial to achieving our goal," he said. "Considering the fact that approximately 85% of breast cancer patients are diagnosed early, in contrast to only around 30% of lung cancer patients, we need to make a concerted effort to increase early diagnosis rates for lung cancer."

“In the past, when patients were diagnosed with cancer at an early stage, they underwent surgery first and then performed adjuvant therapy, but since the tumor was already removed through surgery, it was difficult to objectively know whether it was effective,” he added. “Accordingly, through a paradigm shift called neoadjuvant therapy, which brings adjuvant therapy that was carried out after surgery to the front of the surgery, we are attempting to determine how effective this treatment is by actually looking at the tumor.”

"We expect it to serve as a platform to quickly see how effective the new drug is in early-diagnosed patients, and to allow them to try other treatments if it is not effective,” he said.

“Chemotherapy is generally required in the case of a cancer diagnosis at an advanced stage. However, conventional chemotherapy has various side effects, and patients' conditions may deteriorate or the severity of side effects may gradually increase over time, making it difficult for patients to continue treatment for long periods of time,” he stressed. “To overcome this issue, AstraZeneca is making significant efforts to develop antibody-drug conjugates (ADCs).”

“ADCs have several advantages over traditional chemotherapy, including fewer side effects, longer lasting therapeutic effects, and improved quality of life. These advantages make ADCs a promising new treatment option for cancer patients, both in the early and advanced stages of the disease,” he said. “ADCs have been shown to be effective in treating breast cancer, and we are committed to developing ADCs for lung cancer as well.”

 

◇ Diverse approaches, ADC-IO combinations, and bispecific antibodies
Even though AstraZeneca holds a leading position in the EGFR-TKI field, they are pursuing diverse approaches to conquer the primary obstacle, which is resistance.

Tagrisso has also overcome the T790M mutation that arises after 1st-generation EGFR-TKI treatment and there have been numerous studies to overcome various resistance mechanisms that may occur during or after Tagrisso treatment.

"What sets Tagrisso apart from other EGFR-TKIs is that Tagrisso possesses much more matured data and has demonstrated a unique and highly significant improvement in overall survival (OS)," said Dr. Verma. “This is Tagrisso's special point, which has allowed Tagrisso to become the standard treatment for global first-line therapy.”

However, he emphasized the need to consider other resistance mechanisms beyond EGFR, stating, "For example, while mutations associated with EGFR still play a significant role as resistance mechanisms, drug resistance due to MET mutations occurs in about 30% of patients after EGFR-TKI treatment."

"AstraZeneca is making various attempts using a MET-targeted therapy called Savolitinib," he added. "For patients with distinct resistance mechanisms unrelated to MET mutations, a medication that comprehensively addresses these mechanisms should be utilized, and in this field, antibody-drug conjugates are emerging as a crucial approach."

 

 

AstraZeneca is also strengthening its portfolio in the field of immune oncology. They are actively exploring approaches to maximize treatment efficacy, particularly using bispecific antibodies, rather than monoclonal antibodies.

Dr. Verma mentioned that AstraZeneca is developing bispecific antibodies in the context of immunotherapy, explaining, "As the name suggests, bispecific antibodies are drugs with two arms—one arm recognizes cancer cells, and the other arm mediates immune responses."

Specifically, he added that AstraZeneca currently has three bispecific antibody portfolios, including drugs that target PD1 and CTLA-4, PD1 and TIGIT, and PD1 and TIM-3, a factor known to be involved in the resistance to immunotherapy.

AstraZeneca is also looking for new possibilities in ADCs that are being developed in collaboration with Daiichi Sankyo.

“From a research and development perspective, we believe that ADCs play a critical role in the death of cancer cells and can enhance the response of immunotherapy,” he said. “In response to this, AstraZeneca is conducting extensive research to deliver much-improved treatment outcomes to patients through the combination of ADCs and immunotherapy.

This is not only breaking down the boundaries of drugs but also the boundaries of cancer types. Immunotherapy is expanding treatment opportunities in small cell lung cancer, which has been lacking in treatments.

"Small cell lung cancer patients account for approximately 20% of all lung cancer cases and are known to have much more aggressive characteristics," he said. "In a previous study called CASPIAN, it was shown that adding the immunotherapy drug Imfinzi (ingredient: durvalumab) to chemotherapy improved overall survival in patients with advanced small cell lung cancer, and this has become the standard treatment."

"We are currently conducting the 'ADRIATIC' study to evaluate the improvement in survival when Imfinzi alone or in combination with Imjudo (ingredient: tremelimumab) is added to the conventional concurrent chemotherapy-radiation therapy used for limited-stage small cell lung cancer patients," he added. “Patient enrollment has been completed, and we expect to see results in the first half of next year. If the ADRIATIC study reports positive outcomes, we expect it to be a great help in improving treatment outcomes for patients with limited-stage small cell lung cancer."

 

◇ Expanding clinical trials for better access to treatment
AstraZeneca and the Lung Ambition Alliance are working together to end lung cancer deaths.

The Lung Ambition Alliance places a significant focus on enhancing access to early diagnosis and innovative therapies to alleviate the burden of lung cancer.

Dr. Verma mentioned that treatments are only valuable when they are available to patients, “From a medical standpoint, AstraZeneca's efforts to improve patient accessibility can be broadly summarized into two key components. The first is the inclusion of a wide range of patients in AstraZeneca's global clinical trials.”

"Secondly, AstraZeneca is committed to research and development that leads to definitive improvements in patient outcomes, not marginal improvements," he said. “In other words, we are planning clinical studies to enable health authorities and medical professionals worldwide to assess the significance of our therapies in their respective regions, and by obtaining clear results, we are assisting a diverse range of patients worldwide in benefiting from our treatments.”

AstraZeneca has been also actively working to promote the early detection of lung cancer. Lung cancer is still the leading cause of cancer death, but it is curable if detected early, through surgery or radiation therapy.

To prevent deaths from lung cancer, experts in the field emphasize the necessity of a screening program must be established for at least high-risk groups.

The introduction of low-dose CT, which has relatively low radiation exposure and high accuracy, has enabled the implementation of lung cancer screening programs around the world.

However, in most countries, high-risk groups are defined based on smoking history, leaving non-smokers in a blind spot.

In particular, there are voices that the criteria for high-risk groups should change, as non-smoking Asian women have a higher proportion among lung cancer patients.

In response to this, AstraZeneca is conducting research with lung cancer experts to identify risk factors for lung cancer other than smoking.

South Korea is also conducting research to identify risk factors for non-small cell lung cancer in non-smokers. The results are expected to be released in the first half of next year, and various studies are being conducted to analyze risk factors for lung cancer in Koreans.

Dr. Verma emphasized that the risk factors seen in Asian lung cancer patients are clearly different as the reason for these efforts.

“For example, Taiwan is one of the countries in Asia with well-established lung cancer screening programs. According to a Taiwanese study, family history is a greater risk factor for lung cancer than smoking,” he said. “Although this study does not include all risk factors, it is very meaningful in that we are looking at various risk factors and recognizing their importance."

He also stressed that Asia needs to continue to expand its understanding of who should be screened for lung cancer and what the risk factors are for men and women, including non-smokers, through continuous and diverse discussions.

"In Korea, one out of every four cancer-related deaths are due to lung cancer, despite the presence of an excellent national screening program. It is necessary to widely disseminate the fact that individuals can develop lung cancer due to factors like family history, even if they do not smoke, gradually through campaigns and other means," he said. “AstraZeneca is currently working with Korean researchers and will continue to discuss the issue with stakeholders as soon as meaningful research results are available.”

 

 

◇ Hope Tagrisso to receive coverage in Korea
At WCLC 2023, AstraZeneca achieved another quantum leap by further extending the progression-free survival period of Tagrisso through FLAURA2.

In the first-line treatment, the addition of chemotherapy to Tagrisso extended the progression-free survival period by approximately 9 months.

The combination therapy is expected to improve treatment outcomes in patients with brain metastases and L858R mutations, where the efficacy of single-agent therapy has been relatively poor.

"The advantage of FLAURA2 (Tagrisso + chemotherapy) is that doctors have experience with Tagrisso and are also familiar with the combined chemotherapy," said Dr. Verma. "It might be better received from both the medical team and patient perspectives."

However, in Korea, Tagrisso monotherapy is still not covered by health insurance for first-line treatment. After years of efforts, the final stage of reimbursement has been reached, but patients are still waiting anxiously for the final decision.

"I was a physician who conducted clinical trials in Canada, and Canada also possesses an excellent insurance system and healthcare framework similar to South Korea," he said. "I understand that there are many factors to consider when making reimbursement decisions."

"However, I believe that the healthcare system should be designed to ensure that patients have access to new treatments that have been shown to be significantly more effective than existing treatments," he added. "If there is clear evidence that it improves survival rates and provides better benefits to patients, we should recognize this and work to deliver the treatment to patients earlier."

"I strongly hope that Tagrisso will be covered by insurance for first-line treatment in Korea and understand that many stakeholders are working together to make this happen," he stressed. "I would like to emphasize again that providing treatments that have been shown to be effective can have a positive impact on patients' lives, as well as the healthcare system as a whole.”

 

◇ South Korea is an important partner for AstraZeneca
Many researchers from South Korea are actively engaged in AstraZeneca's research.

Dr. Verma explained that Korea is a key partner of AstraZeneca, ranking second after the United States in terms of the number of research projects and patients.

"Korea is a very important partner for AstraZeneca. Korea was the third-leading country in the world for AstraZeneca's cancer drug trials in 2022, after the United States and China, but in 2023, Korea has moved up to second place, right behind the United States," he said.

"Korea plays a very crucial role in AstraZeneca's cancer drug research and development, as the number of patients participating in cancer drug trials in Korea is the second-highest in the world," he added. "The level of care provided by Korean doctors and the level of clinical research conducted in Korea are exemplary for the rest of the world."

"I am aware of the many talented Korean researchers who are conducting cutting-edge research," he said. "This is why AstraZeneca has established many partnerships in Korea, and we want to continue this relationship in the future."

"I joined the pharmaceutical industry because I wanted to help patients around the world, and I was particularly impressed by AstraZeneca's vision and strategy in the field of oncology," he said. "Through these visions, I want to dedicate myself to helping cancer patients not only in Korea but around the world."