Frontline Osimertinib Plus Chemo Wins Canadian Approval for EGFR+ Superior NSCLC

Well being Canada has accepted osimertinib (Tagrisso) together with pemetrexed and platinum-based chemotherapy for the frontline therapy of sufferers with regionally superior or metastatic non–small cell lung most cancers (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations.¹

The regulatory resolution was supported by knowledge from the part 3 FLAURA2 trial (NCT04035486), which confirmed that osimertinib plus chemotherapy led to a statistically important enchancment in progression-free survival (PFS) in contrast with osimertinib alone (HR, 0.62; 95% CI, 0.49-0.79; P < .001). Per investigator evaluation, the median PFS was 25.5 months (95% CI, 24.7-not calculable [NC]) for osimertinib plus chemotherapy (n = 279) vs 16.7 months (95% CI, 14.1-21.3) for osimertinib alone (n = 278).

Per blinded unbiased central assessment (BICR) evaluation, osimertinib plus chemotherapy led to a median PFS of 29.4 months (95% CI, 25.1-NC) in contrast with 19.9 months (95% CI, 16.6-25.3) with osimertinib alone (HR, 0.62; 95% CI, 0.48-0.80).

“The FLAURA2 trial confirmed outcomes demonstrating that sufferers skilled a considerably longer time with out development than these sufferers on commonplace of care,” Barbara Melosky, MD, FRCPC, medical oncologist and medical professor of medication on the College of British Columbia, said in a information launch.1 “This approval is nice information for physicians and sufferers and additional helps us to match the precise affected person to the precise therapy to get the very best outcomes.”

In February 2024, the FDA accepted osimertinib plus platinum-based chemotherapy to be used in sufferers with regionally superior or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved take a look at.3 The European Fee accepted osimertinib plus pemetrexed and platinum-based chemotherapy in the identical indication on July 5, 2024.⁴

Each of these regulatory choices had been supported by knowledge from FLAURA2, which enrolled sufferers at the very least 18 years of age (or at the very least 20 years of age in Japan) with beforehand untreated regionally superior or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations. Sufferers had been required to have a World Well being Group efficiency standing of 0 or 1. These with central nervous system (CNS) metastases had been allowed to enroll in the event that they had been neurologically secure.²

The worldwide, open-label research randomly assigned sufferers 1:1 to obtain 80 mg of osimertinib per day plus 500 mg/m² of pemetrexed and both 75 mg/m² of cisplatin or space below the curve 5 of carboplatin on day 1 of every 21-day cycle for 4 cycles; or 80 mg of osimertinib per day alone. Remedy continued till illness development, unacceptable toxicity, or different discontinuation standards had been met.

Investigator-assessed PFS per RECIST 1.1 standards served because the trial’s major finish level. Secondary finish factors included general survival (OS), goal response fee (ORR), length of response (DOR), illness management fee, depth of response, and time to second development.

Further knowledge confirmed that in sufferers who had CNS metastases at baseline, osimertinib plus chemotherapy (n = 116) resulted in a median PFS of 24.9 months (95% CI, 22.0-NC) vs 13.8 months (95% CI, 11.0-16.7) with osimertinib alone (n = 110; HR, 0.47; 95% CI, 0.33-0.66). In sufferers with out CNS metastases, the median PFS was 27.6 months (95% CI, 24.7-NC) for osimertinib plus chemotherapy (n = 163) vs 21.0 months (95% CI, 16.7-30.5) for osimertinib alone (n = 168; HR, 0.75; 95% CI, 0.55-1.03).

Sufferers within the osimertinib/chemotherapy arm achieved an ORR of 83% (95% CI, 78%-87%) in contrast with 76% (95% CI, 70%-80%) for these within the osimertinib monotherapy arm per investigator evaluation. The BICR-assessed ORRs had been 92% (95% CI, 88%-95%) and 83% (95% CI, 78%-87%), respectively. The investigator-assessed median DOR was 24.0 months (95% CI, 20.9-27.8) for osimertinib plus chemotherapy vs 15.3 months (95% CI, 12.7-19.4) for osimertinib alone.

On the time of the evaluation, OS knowledge had been at 27% maturity, and a development favoring osimertinib plus chemotherapy was noticed (HR, 0.90; 95% CI, 0.65-1.24; P = .52). The respective 12- and 24-month OS charges had been 89% (95% CI, 84%-92%) and 79% (95% CI, 73%-83%) within the osimertinib plus chemotherapy arm. These charges had been 92% (95% CI, 88%-95%) and 73% (95% CI, 67%-78%), respectively, within the osimertinib monotherapy arm.

Concerning security, any-grade opposed results (AEs) occurred in all sufferers within the osimertinib plus chemotherapy arm vs 97% of these within the osimertinib monotherapy arm. The charges of grade 3 or greater AEs had been 64% and 27%, respectively. The respective charges of great AEs had been 38% and 19%.

AEs led to discontinuation of osimertinib in 11% of sufferers within the experimental arm vs 6% of sufferers within the management arm. The charges of AEs resulting in dose interruptions of osimertinib had been 43% and 19%, respectively. The respective charges of AEs resulting in dose reductions of osimertinib had been 10% and three%.

References

1. Well being Canada approves Tagrisso with the addition of chemotherapy for sufferers with EGFR-mutated superior lung most cancers. Information launch. AstraZeneca. July 12, 2024. Accessed July 12, 2024. https://www.biospace.com/article/releases/health-canada-approves-tagrisso-and-174-with-the-addition-of-chemotherapy-for-patients-with-egfr-mutated-advanced-lung-cancer
2. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or with out Chemotherapy in EGFR-Mutated Superior NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
3. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung most cancers. FDA. February 16, 2024. Accessed July 12, 2024. https://www.fda.gov/medicine/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer
4. Tagrisso with the addition of chemotherapy accepted within the EU as new 1st-line therapy for sufferers with EGFR-mutated superior lung most cancers. Information launch. AstraZeneca. July 5, 2024. Accessed July 12, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/tagrisso-with-the-addition-of-chemotherapy-approved-in-the-eu-as-new-1st-line-treatment-for-patients-with-egfr-mutated-advanced-lung-cancer.html