AZ's 'Tagrisso' Succeeds in Combination Chemotherapy Clinical Trial... Will It Widen the Gap with Yuhan's 'Reclaza'?

World Lung Cancer Conference Unveils 'FLAURA2'
mPFS Extended by 9 Months Compared to Tagrisso Alone
Safety "Consistent with Existing Treatment Profiles"

Yuhan & Janssen to Counter with 'MARIPOSA' Clinical Data at October ESMO

AstraZeneca (AZ)'s non-small cell lung cancer treatment 'Tagrisso (Osimertinib)' has announced improved efficacy through combination therapy with chemotherapy, solidifying its dominance as the 'backbone treatment for non-small cell lung cancer.' Amid intensifying competition with Yuhan Corporation's competing new drug 'Rybrevant (Lazertinib),' Tagrisso is making a full-scale move to outpace Rybrevant globally by improving the efficacy of combination therapy and domestically by securing first-line treatment reimbursement.

AstraZeneca's non-small cell lung cancer treatment 'Tagrisso (active ingredient Osimertinib)'
[Photo by Korea AstraZeneca]

On the morning of the 11th, AZ presented the results of the 'FLUARA2' clinical trial, which aimed to prove the efficacy and safety of combination therapy of Tagrisso with pemetrexed and platinum-based (cisplatin, carboplatin, etc.) chemotherapy, at the 2023 International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC) held in Singapore. In the clinical trial involving 557 patients with locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation non-small cell lung cancer, the combination therapy group showed a median progression-free survival (mPFS) approximately 9 months longer than the control group receiving Tagrisso monotherapy. The risk of cancer progression or death was reduced by 38%.

PFS refers to the period during which the cancer does not progress after treatment. In other words, the median time to cancer recurrence, which is 16.7 months with Tagrisso monotherapy, was delayed by 8.8 months to 25.5 months when combined with chemotherapy. This was observed across all subgroups regardless of gender, race, age, smoking history, mutation type, or central nervous system metastasis status. An independent central review committee (BICR) evaluation also confirmed an mPFS extension of 9.5 months, from 19.9 months with Tagrisso monotherapy to 29.4 months with combination therapy.

Another key indicator of anticancer drug efficacy, overall survival (OS), was not disclosed due to 'immature data.' Unlike PFS, which measures the time until patient death or cancer recurrence after treatment, OS refers to the period from the start of treatment to the patient's death from any cause. It requires all participating patients to have died to fully analyze the data, thus taking more time to confirm. AZ explained, "Although the data are still immature, a favorable trend was observed for Tagrisso-chemotherapy combination therapy." The objective response rate (ORR), set as one of the secondary efficacy endpoints, was 83% for combination therapy and 76% for monotherapy.

Regarding safety, a major concern with chemotherapy combination, AZ stated, "The safety results and treatment discontinuation rates due to adverse events were consistent with the profiles observed for each treatment." Grade 3 or higher serious adverse events occurred in 64% of the combination therapy group, higher than 27% in the Tagrisso monotherapy group. Additionally, treatment discontinuation occurred in 11% of the combination group and 4% of the monotherapy group.

Although significant side effects were observed, this is considered largely attributable to the inherent nature of chemotherapy, which inevitably increases adverse events. Compared to another investigator-initiated trial of first-line Tagrisso-chemotherapy combination therapy, the 'OPAL' trial, the efficacy was maintained while side effects were significantly reduced. The OPAL trial, involving 67 patients, showed an mPFS of 31.0 months, similar to FLUARA2, but grade 3 or higher adverse events reached 89.6%, and 15% of patients had to discontinue treatment due to side effects.

Susan Galbraith, AZ's Senior Vice President of Oncology Research and Development, said, "The strong results confirmed in FLUARA2 provide further evidence supporting Tagrisso's role as the backbone treatment for EGFR mutation non-small cell lung cancer. We expect it to further delay resistance development and disease progression in patients with high unmet needs."

The FLUARA2 clinical trial results were reportedly presented in the plenary session, where key announcements are made, attracting significant attention on-site. This large-scale follow-up trial conducted by Tagrisso, considered the standard first-line treatment for non-small cell lung cancer, and the recent designation of this combination therapy as a breakthrough therapy by the U.S. Food and Drug Administration (FDA) last month, likely contributed to the heightened interest. Breakthrough therapy designation is granted to treatments expected to demonstrate superior efficacy compared to existing therapies, offering practical benefits such as reduced costs and time during the approval process.

Scenes from the 2022 International Association for the Study of Lung Cancer World Conference on Lung Cancer (IASLC 2022 WCLC) held last year in Vienna, Austria.
[Photo by International Association for the Study of Lung Cancer]

Furthermore, the rapid pursuit of Tagrisso by Yuhan Corporation's non-small cell lung cancer new drug 'Rybrevant (Lazertinib)' has also raised expectations for the FLUARA2 announcement. The two drugs are competing domestically to secure first-line treatment reimbursement and globally for dominance in first-line combination therapy. While Tagrisso struggled for five years to pass the first hurdle of reimbursement approval by the Cancer Quality Review Committee since its first-line treatment approval in 2018, only clearing it in March this year, Rybrevant passed the committee just two months after its approval in June, significantly narrowing the gap. However, Tagrisso accelerated its goal of 'reimbursement within the year' by passing the second hurdle, the Drug Reimbursement Evaluation Committee, on the 7th.

Globally, Yuhan Corporation, which licensed Rybrevant to big pharma Janssen for collaboration, also disclosed additional data from the 'Chrisalis 2' clinical trial combining Janssen's targeted antibody therapy 'Rybrevant (Amivantamab)' with chemotherapy, as well as Asian subgroup data from the Rybrevant first-line monotherapy global trial 'LASER 301' at the World Conference on Lung Cancer.

However, the real showdown is expected at the European Society for Medical Oncology (ESMO) conference next month in Madrid, Spain. This is because the results of the 'MARIPOSA' clinical trial, which set Tagrisso monotherapy as the control group against the Rybrevant-Rybrevant combination therapy, will be released. Janssen CEO Joaquin Duato has identified the Rybrevant-Rybrevant combination therapy as one of the key pipelines expected to generate annual sales exceeding $5 billion (approximately 6.685 trillion KRW) in the future, indicating high expectations from both companies. Since the LASER 301 trial showed an mPFS of 20.6 months, the goal is to achieve an mPFS value surpassing this and exceeding FLUARA2.

This content was produced with the assistance of AI translation services.