For AstraZeneca, a genetic mutation gave rise to its blockbuster pipeline in lung cancer. In 2003, the pharmaceutical giant embarked on a complex journey that was almost destined to fail. At the time, Iressa (gefitinib), a lung cancer drug targeting EGFR gene mutations, was approved by the U.S. FDA, but was withdrawn from the market two years later due to poor efficacy.

However, in the years that followed, AstraZeneca deepened its understanding of the patient subtypes that responded to the drug. Based on studies in patients with EGFR mutations, Iressa was re-approved in 2015. Shortly thereafter, the company secured its first approval with the third-generation EGFR-targeted drug Tagrisso (osimertinib), which is now regarded as the "cornerstone" of its lung cancer portfolio.

The precision medicine strategy revitalized the company's oncology efforts and continues to this day. In a recently presented study, Tagrisso combined with chemotherapy showedlong-term overall survival benefitsin patients with EGFR-mutated non-small cell lung cancer. AstraZeneca has built a pipeline around EGFR—the recent approval of Datrowayfurther strengthens its position in lung cancer and supports its ambitious goal of treatingmore than halfof lung cancer patients by 2030.

Here, we spoke with Arun Krishna, Vice President and Head of AstraZeneca's Lung Cancer Program, to explore how its strategy has evolved around a single mutation.

This interview has been edited for length and style.

PHARMAVOICE: From AstraZeneca's perspective, why has EGFR become such an important target?

ARUN KRISHNA:Most people associate lung cancer with smokers, but we know clearly that 20% of lung cancer patients have never smoked. So, our journey began in the EGFR space because we recognized scientifically that oncogenic drivers like EGFR cause lung cancer in non-smokers. Ten years ago, we started with the first approval of Tagrisso in theT790Mmutation, beginning with a very small population in the second-line setting, and then rapidly advanced to the first-line setting through the Flaura study, which demonstrated an overall survival benefit. Since then, Tagrisso has become the standard of care for EGFR-mutated lung cancer.

We are working to identify lung cancer earlier. Currently, we not only have EGFR data in the metastatic stage, but also data in the early stages. Tagrisso is the foundational treatment for EGFR patients across all stages. Twenty years ago, the only option for patients was chemotherapy. Today, science has made tremendous progress.

AstraZeneca has multiple lung cancer drugs, and Datroway is one of the latest approvals. What is the importance of having multiple drugs targeting the same mutation?

There are different patient types within the EGFR space. Some may benefit from monotherapy, while others may benefit from combination therapy, because combination therapy is the way forward. No single treatment modality can address a specific type of cancer, so we are exploring multiple avenues to attack cancer through combination regimens.

AstraZeneca aims to treat more than half of lung cancer patients with one or more of its drugs by 2030. How will you achieve this?

Achieving this goal requires a multi-pronged approach. One is through drug development, ensuring we focus not only on single agents but also on combinations. Second, we are moving into earlier stages of the patient journey. But that is not enough, because we know lung cancer screening rates are very low, especially in the U.S. There is currently no screening policy for never-smokers. Therefore, a major goal over the next three to five years is to work with healthcare systems, the clinical community, and patient advocacy organizations to raise awareness of screening. Additionally, we are collaborating with universities and academic centers to develop early detection programs for non-smokers. These two aspects complement each other: we rapidly develop drugs and bring them to the clinic, while also working to drive the rapid adoption of screening strategies across the population.

EGFR is now a well-recognized target in lung cancer, but it was not always so. Does the infrastructure needed to achieve such breakthroughs still exist today?

We are at the forefront of a scientific and technological explosion. We will discover more subtypes and mutations. But there are still gaps to bridge. We have come a long way, but we still need to work at the grassroots and community levels to ensure clinicians are informed and patients proactively request biomarker testing, so they receive the right treatment at the right time and achieve the best possible survival outcomes.