New Results Uphold Frontline Osimertinib Benefit Against CNS Mets in NSCLC

In data presented at the 2017 ESMO Asia Congress, updated results again sustained the benefit of frontline osimertinib (Tagrisso) in patients with <em>EGFR</em>-positive advanced non&ndash;small cell lung cancer (NSCLC) and CNS metastases at baseline.

In data presented at the 2017 ESMO Asia Congress, updated results again sustained the benefit of frontline osimertinib (Tagrisso) in patients withEGFR-positive advanced non—small cell lung cancer (NSCLC) and CNS metastases at baseline.

In a subgroup analysis from the phase III FLAURA trial, which included 128 patients with at least 1 measurable and/or nonmeasurable CNS lesion at baseline, among 61 patients who received osimertinib, the CNS objective response rate (ORR) was 66%, compared to 43% (odds ratio, 2.5; 95% CI 1.2-5.2;P= .011) in 67 patients who received standard EGFR TKI therapy with erlotinib (Tarceva) or gefitinib (Iressa).

Osimertinib reduced the risk of CNS disease progression or death by 52% (HR, 0.48; 95% CI, 0.26-0.86; nominalP= .014). The rate of disease progression resulting from the development of new CNS lesions was also lower with osimertinib, at 12% versus 30%.

“CNS metastases, including brain metastases, are a common and very disabling complication of advancedEGFRmutation—positive NSCLC. They are notoriously difficult to treat, as existing oral therapies are often unable to effectively cross the blood-brain barrier. The CNS efficacy results for osimertinib in the FLAURA trial suggest improved clinical outcomes in an area of great unmet medical need,” lead author Johan Vansteenkiste, MD, PhD, respiratory oncologist at the University Hospital KU Leuven, Belgium, said in a statement.

In the double-blind FLAURA trial, 556 treatment-naïve patients withEGFR-positive locally advanced or metastatic NSCLC were randomly assigned to osimertinib (n = 279) or an existing TKI (n = 277). Patients with CNS metastases were allowed on the trial and all had exon 19 deletions or L858R mutations. Daily oral therapy was given with 80 mg of osimertinib, 250 mg of gefitinib, or 150 mg of erlotinib.2

Median progression-free survival (PFS) was 18.9 months (95% CI, 15.2-21.4), for osimertinib compared with 10.2 months (95% CI, 9.6-11.1) for the control group, an 8.7-month improvement in median PFS (hazard ratio [HR], 0.46; 95% CI, 0.37-0.57;P<.0001). Improvements were seen in all prespecified subgroups, including patients with and without brain metastases Medians had not yet been reached for overall survival, but at just 25% maturity, HR favored osimertinib at 0.63, a 37% reduction in the risk of death (95% CI, 0.45-0.88;P= .0068). However, those results have not yet been shown to be meaningful. There had been 58 deaths in the osimertinib arm and 83 in the control group.

The ORR with osimertinib was 80% compared with 76% for erlotinib and gefitinib (odds ratio [OR], 1.28, 0.85-1.93;P= .2335). The median duration of response with osimertinib was 17.2 months versus 8.5 months in the comparator arm.

The most common any grade adverse events (AEs) were diarrhea (58%) and dry skin (32%) in the experimental group compared with diarrhea (57%) and dermatitis acneiform (48%) in the control group.

Overall, 33.7% of patients experienced a grade ≥ 3 AE in the osimertinib group compared with 44.8% for erlotinib and gefitinib. Patients in the osimertinib group were less like to discontinue treatment because of AEs (13.3% vs 18.1%).

In October 2017, the FDA awarded a breakthrough therapy designation to osimertinib for the first-line treatment of patients with metastaticEGFRmutation-positive NSCLC. The drug is approved as a treatment for patients with metastaticEGFR T790Mmutation—positive NSCLC following prior treatment with an EGFR TKI.


  1. Vansteenkiste J, et al. CNS Response to Osimertinib Vs. Standard-of-Care EGFR-TKI as First-Line Treatment in Patients with EGFRm Advanced NSCLC: FLAURA. Presented at ESMO Asia 2017 Congress; November 17-19, 2017; Singapore. Abstract LBA5.
  2. Ramalingam S, Reungwetwattana T, Chewaskulyong B, et al. Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with EGFRm advanced NSCLC: FLAURA. Presented at: 2017 ESMO Congress; Madrid, Spain; September 9-12, 2017. Abstract LBA2_PR.