FDA Grants Priority Review to Osimertinib for EGFR+ Stage III NSCLC


Key Takeaways

  • Osimertinib significantly improved PFS in unresectable, stage III NSCLC with EGFR mutations post-chemoradiotherapy.
  • Median PFS was 39.1 months for osimertinib versus 5.6 months for placebo.


The FDA has granted priority review to the supplemental new drug application (sNDA) seeking the approval of osimertinib (Tagrisso) for the treatment of patients with unresectable, stage III non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R mutations following chemoradiotherapy.1

The sNDA is supported by data from the phase 3 LAURA trial (NCT03521154), which showed that treatment with osimertinib led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with placebo in this patient population following definitive chemoradiotherapy (HR, 0.16; 95% CI, 0.10-0.24; P < .001). Findings presented at the 2024 ASCO Annual Meeting showed that patients treated with osimertinib (n = 143) experienced a median PFS of 39.1 months (95% CI, 31.5-not calculable [NC]) vs 5.6 months (95% CI, 3.7-7.4) for those given placebo (n = 73).2

“Priority review of [osimertinib] in this early-stage curative setting is important for patients who currently have no targeted treatments available. We look forward to close collaboration with the FDA on an accelerated path to bring [osimertinib] to patients as a potential new standard of care as quickly as possible,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, stated in a news release.1 “[Osimertinib] continues to serve patients as a backbone therapy in EGFR-mutated lung cancer, extending PFS in the LAURA trial by more than 3 years and reinforcing the importance of testing for EGFR mutations at the time of diagnosis."

The randomized, double-blind LAURA trial enrolled patients at least 18 years of age (or at least 20 years of age in Japan) with locally advanced, unresectable stage III NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations. Patients also need to have a World Health Organization performance status of 0 or 1. The maximum interval between the last dose of chemoradiotherapy and randomization was 6 weeks.

Patients were randomly assigned 2:1 to receive 80 mg of osimertinib or matching placebo once per day. Stratification factors included method of chemoradiotherapy (concurrent or sequential), stage (IIIA vs IIIB/C), and location (China vs non-China). Treatment continued in both arms until blinded independent central review (BICR)–assessed disease progression per RECIST 1.1 criteria, toxicity, or other discontinuation criteria were met. Following BICR-confirmed progression, patients in both arms were allowed to receive open-label osimertinib.

Tumor assessments were conducted via chest CT/MRI and brain MRI at baseline, then once every 8 weeks for the first 48 weeks, and then once every 12 weeks until BICR-assessed disease progression.

BICR-assessed PFS per RECIST 1.1 criteria served as the trial’s primary end point. Key secondary end points included overall survival (OS), central nervous system PFS, and safety.

At data cutoff, treatment was ongoing for 56% of patients (n = 80) in the osimertinib arm vs 10% (n = 7) in the placebo arm. Reasons for discontinuation in the experimental arm included disease progression (25%), adverse effects (AEs; 13%), patient decision (3%), start of other anticancer therapy (n = 1%), and other (2%). Reasons for discontinuation in the control arm included disease progression (74%), AEs (7%), patient decision (4%), start of other anticancer therapy (1%), incorrect initiation of study treatment (1%), and other (3%). Eighty-one percent of patients in the placebo arm crossed over to receive open-label osimertinib following disease progression, and 28% of patients in the experimental arm received osimertinib after progression.

Additional data showed treatment with osimertinib led to an investigator-assessed median PFS of 38.9 months (95% CI, 26.7-NC) compared with 7.3 months (95% CI, 5.5-10.3) for placebo (HR, 0.19; 95% CI, 0.12-0.29; P < .001).

Notably, BICR-assessed PFS favored osimertinib across all subgroups.

Patients in the osimertinib arm achieved a BICR-assessed objective response rate of 57% (95% CI, 49%-66%) vs 33% (95% CI, 22%-45%) for those treated with placebo. The disease control rates were 89% (95% CI, 83%-94%) and 79% (95% CI, 68%-88%), respectively. Patients given osimertinib experienced a median duration of response of 36.9 months (95% CI, 30.1-NC) vs 6.5 months (95% CI, 3.6-8.3) for those given placebo.

Sixty-eight patients in the placebo arm experienced new lesions per BICR assessment compared with 22 patients in the osimertinib arm. Sites of new lesions included brain (osimertinib, n = 8; placebo, n = 29), lung (n = 6; n = 29), liver (n = 3; n = 7), lymph nodes (n = 1; n = 7), bone (n = 1; n = 1), adrenal (n = 1; n = 0), peritoneum/omentum (n = 1; n = 0), pelvis (n = 1; n = 0), spleen (n = 0; n = 1), and other (n = 1; n = 0).

Although OS data were 20% mature at data cutoff, a trend favoring osimertinib was observed (HR, 0.81; 95% CI, 0.42-1.56; P = .530). The median OS was 54.0 months (95% CI, 46.5-NC) for osimertinib and not reached (95% CI, 42.1-NC) for placebo. The 36-month OS rates were 84% and 74%, respectively.

Regarding safety, any-grade AEs occurred in 98% of patients in the osimertinib arm and 88% of patients in the placebo arm. The rates of grade 3 or higher AEs were 35% and 12%, respectively, and AEs led to death in 2% of patients in the osimertinib group vs 3% of patients in the placebo group. Serious AEs were reported in 38% of patients in the experimental arm vs 15% in the placebo arm. AEs led to discontinuation, dose reduction, and dose interruption in 13%, 8%, and 56% of patients in the osimertinib arm, respectively. Those respective rates were 5%, 1%, and 25% in the control arm.

Any-grade AEs that were possibly causally related were observed in 80% of patients in the osimertinib arm vs 41% of patients in the control arm. The rates of grade 3 or higher AEs that were possibly causally related were 13% for osimertinib and 3% for placebo. One patient (1%) in the experimental arm experienced an AE that was possibly causally related that led to death; no death related to these types of AEs occurred in the placebo arm. The rates of any serious AEs that were possibly causally related were 8% for osimertinib and 1% for placebo.

The most common any-grade AEs of any cause reported in at least 10% of patients included radiation pneumonitis (osimertinib, 48%; placebo, 38%), diarrhea (36%; 14%), rash (24%; 14%), COVID-19 (20%; 8%), paronychia (17%; 1%), cough (16%; 10%), decreased appetite (15%; 5%), dry skin (13%; 5%), pruritus (13%; 7%), stomatitis (12%; 3%), decreased white blood cell count (12%; 3%), pneumonia (11%; 8%), anemia (10%; 4%), and musculoskeletal chest pain (3%; 12%).


  1. Tagrisso (osimertinib) granted priority review in the US for patients with unresectable, stage III EGFR-mutated lung cancer. News release. AstraZeneca. June 10, 2024. Accessed June 10, 2024.
  2. Ramalingam SS, Kato T, Dong X, et al. Osimertinib (osi) after definitive chemoradiotherapy (CRT) in patients (pts) with unresectable stage (stg) III epidermal growth factor receptor-mutated (EGFRm) NSCLC: primary results of the phase 3 LAURA study. J Clin Oncol. 2024;42(suppl 17):LBA4. doi:10.1200/JCO.2024.42.17_suppl.LBA4
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