China’s NMPA Approves First-Line Osimertinib Plus Chemotherapy in EGFR-Mutant NSCLC

China’s National Medical Products Administration (NMPA) has approved osimertinib (Tagrisso) for use in combination with pemetrexed (Alimta) and platinum-based chemotherapy for the frontline treatment of adult patients with locally advanced or metastatic EGFR-mutant non–small cell lung cancer (NSCLC) whose tumors have exon 19 deletions or exon 21 L858R mutations.¹

The approval was based on data from the phase 3 FLAURA2 trial (NCT04035486) which were published in the New England Journal of Medicine, and findings from a prespecified exploratory analysis in Chinese patients that were presented at the 2023 ESMO Asia Congress.^2,3

Among the Chinese population (n = 131) the combination of osimertinib and chemotherapy (n = 67) extended both investigator-assessed and blinded independent central review (BICR)–assessed progression-free survival (PFS) vs osimertinib alone (n = 64; HR, 0.56; 95% CI, 0.34-0.92 and HR, 0.58; 95% CI, 0.34-1.01, respectively). The median PFS per investigator assessment was 27.4 months (95% CI, 22.3-not calculable [NC]) with the combination vs 22.3 months (95% CI, 16.7-25.0) with osimertinib alone. Per BICR, the median PFS was 33.2 months (95% CI, 25.1-NC) with the combination vs 22.0 months (95% CI, 16.6-NC) with osimertinib alone. Chinese patients also displayed a trend toward improved overall survival (OS) with the combination (HR, 0.97; 95% CI, 0.45-2.06), although data maturity was only 21%.³

“The approval of osimertinib with the addition of chemotherapy in China is critical for the treatment of the largest population of patients with EGFR-mutated lung cancer worldwide. These patients will now have a choice of two highly effective osimertinib-based options for first-line treatment, allowing physicians to tailor their approach to their patients. This is especially important for those with a poorer prognosis, such as cancer that has spread to the brain or those who have L858R mutations,” Ying Cheng, MD, principal investigator and professor and director of Jilin Lung Cancer Diagnosis and Treatment Centre in China, said in the news release.¹

The randomized, open-label, multi-center, global phase 3 FLAURA2 trial enrolled patients with stage IIIB to IIIC or stage IV EGFR-mutant NSCLC. Patients received 80 mg of osimertinib in the form of once-daily oral tablets in combination with pemetrexed 500 mg/m2 plus cisplatin 75mg/m2 or carboplatin at an area under the curve of 5 every 3 weeks for four cycles, followed by osimertinib with pemetrexed maintenance every 3 weeks; or osimertinib alone.¹

The primary end point was investigator-assessed PFS. Secondary end points included OS, objective response rate (ORR), duration of response (DOR), and safety.

Results from the primary analysis of the overall population indicated that the addition of osimertinib to chemotherapy improved both investigator-assessed and BICR-assessed PFS vs osimertinib alone (HR, 0.62; 95% CI, 0.49-0.79; P <.0001 and HR, 0.62; 95% CI, 0.48-0.80; P =.0002, respectively). The median PFS per investigator assessment was 25.5 months with the combination vs 16.7 months with osimertinib alone. Per BICR, the median PFS was 29.4 months with the combination vs 19.9 months with osimertinib alone.²

Investigators also reported a trend toward improved OS with the combination, although data had only reached 41% maturity (HR, 0.75; 95% CI, 0.57-0.97).²

Results from the primary analysis served as the basis for both the FDA and Japanese approvals of osimertinib plus platinum-based chemotherapy in the overall patient population.^4,5

Additional results from the Chinese population demonstrated that the percentage and duration of objective responses were superior with the combination. The investigator-assessed ORR was 87% with the combination vs 77% with osimertinib alone, with median DORs of 26.2 months (95% CI, 20.7-NC) and 20.8 months (95% CI, 15.3-23.5), respectively.

The safety profile of the combination was largely manageable and comparable to that of each individual agent, although higher rates of adverse effects (AEs) and treatment-related AEs occurred with the combination.

“[Osimertinib] with the addition of chemotherapy in FLAURA2 has not only shown unprecedented PFS in the overall trial population, but also among Chinese patients, reducing the risk of disease progression by nearly half. This approval reinforces [osimertinib] as a backbone therapy in EGFR-mutated lung cancer and acknowledges its important role, as monotherapy or with chemotherapy, in addressing the high prevalence of this disease in Asian countries and China, specifically,” Dave Fredrickson, executive vice president of the Oncology Business Unit, AstraZeneca, added.¹

The study is ongoing and will continue to evaluate OS.

References

1. Tagrisso with the addition of chemotherapy approved in China as 1st-line treatment for patients with EGFR-mutated advanced lung cancer. News release. AstraZeneca. June 26, 2024. Accessed June 26, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-with-the-addition-of-chemotherapy-approved-in-china-as-1st-line-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer.html
2. Planchard D, Janne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
3. Cheng Y, Yu Y, Fan Y, et al. First-line (1L) osimertinib (osi) ± platinum-pemetrexed in patients (pts) with EGFRm advanced NSCLC: FLAURA2 China cohort. Ann Oncol. 2023;34(suppl 4):S1689. doi:10.1016/j.annonc.2023.10.640
4. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung cancer. FDA. February 16, 2024. Accessed June 26, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer
5. Tagrisso with the addition of chemotherapy approved in Japan as new 1st-line treatment for patients with EGFR-mutated advanced lung cancer. News release. AstraZeneca. June 25, 2024. Accessed June 26, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-addition-chemotherapy-approved-japan-new-first-line-treatment-patients-egfr-mutated-advanced-lung-cancer.html