ASCO: AstraZeneca's Tagrisso, Imfinzi set new lung cancer milestone—earning ovation

AstraZeneca’s Tagrisso has achieved significant progress in the treatment of stage 3 EGFR-mutated non-small cell lung cancer (NSCLC), showing an unprecedented 84% improvement in progression-free survival compared to a placebo. This breakthrough was highlighted during the American Society of Clinical Oncology (ASCO) 2024 annual meeting and is expected to become the new standard of care for this condition.

Key findings from the phase 3 LAURA trial demonstrated that patients treated with Tagrisso experienced a median of 39.1 months without disease progression, as opposed to just 5.6 months for those on a placebo. Additionally, two years post-treatment, only 6% of patients on Tagrisso developed brain metastases compared to 28% in the control group. These benefits were consistent across various subgroups, including different stages of the disease (3a, 3b, and 3c), as published in The New England Journal of Medicine.

While data on overall life expectancy remain preliminary, early results indicate a 19% reduction in the risk of death for patients on Tagrisso compared to those on a placebo. This is notable even though 81% of the placebo group eventually received Tagrisso following disease progression. Suresh Ramalingam, M.D., the principal investigator of the trial, noted that mature overall survival data would be available within the next 18 months to two years.

The success of Tagrisso in this trial positions it to potentially fill a treatment gap left by AstraZeneca’s other drug, Imfinzi. Previously considered the standard of care for stage 3 NSCLC based on the phase 3 PACIFIC trial, Imfinzi only showed a modest 9% reduction in the risk of progression or death in patients with EGFR mutations. With such overwhelming evidence from the LAURA trial, Tagrisso is poised to become the preferred treatment.

Imfinzi itself has had recent success in another area. In the phase 3 ADRIATIC study, Imfinzi reduced the risk of death by 27% compared to a placebo in patients with limited-stage small cell lung cancer (LS-SCLC) following concurrent chemoradiotherapy. The ADRIATIC trial, presented at the ASCO meeting, further demonstrated that patients treated with Imfinzi had a median overall survival of 55.9 months versus 33.4 months for those on a placebo. Furthermore, Imfinzi cut the risk of disease progression or death by 24%, with patients going a median of 16.6 months without progression compared to 9.2 months for the placebo group.

LS-SCLC, accounting for about 30% of small cell lung cancer cases, has not seen new treatments in approximately 40 years, making these findings particularly significant. Cristian Massacesi, M.D., AstraZeneca’s chief medical officer, pointed out that the focus on ADRIATIC’s data might shift due to the absence of results from a third study arm evaluating the combination of Imfinzi with AZ’s CTLA4 inhibitor Imjudo. Although the combination arm has not yet been analyzed, David Spiegel, M.D., who leads the ADRIATIC study, assured that the trial was designed to first assess the primary endpoints for Imfinzi versus placebo before moving on to the combination analysis as a secondary endpoint.

Imjudo’s track record in lung cancer has been less stellar, having only shown success in combination with Imfinzi and chemotherapy for first-line metastatic NSCLC, and even then, not competitively against other PD-1 inhibitors. However, Massacesi suggested that Imjudo could offer long-term benefits based on its performance in other trials, though he refrained from specifying what level of improvement would be considered meaningful in combination with Imfinzi.

In summary, AstraZeneca's Tagrisso is set to redefine the standard of care for stage 3 EGFR-mutated NSCLC thanks to its substantial impact on disease progression. Concurrently, Imfinzi continues to show promise, particularly in LS-SCLC, marking a significant advancement in lung cancer treatment paradigms.