TAGRISSO Reduced the Risk of Disease Recurrence in the Brain by 82% in the Adjuvant Treatment of Early-Stage EGFR-Mutated Lung Cancer
ADAURA Phase III trial data at ESMO reinforce the proven clinical activity of TAGRISSO in treating central nervous system metastases
WILMINGTON, Del.--(BUSINESS WIRE)--Results from a prespecified exploratory analysis of the positive ADAURA Phase III trial showed AstraZeneca?s TAGRISSO??(osimertinib) demonstrated a clinically meaningful improvement in central nervous system (CNS) disease-free survival (DFS) in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC), after complete tumor resection.
While up to 30% of all patients with NSCLC may be diagnosed early enough to have potentially curative surgery, disease recurrence is still common in early-stage disease.1-3?CNS recurrence, when cancer spreads to the brain, is a frequent complication of EGFRm NSCLC and these patients have an especially poor prognosis.4,5
Results were presented on September 19, 2020 during the Presidential Symposium of the European Society for Medical Oncology (ESMO) Virtual Congress 2020 (abstract #LBA1) and simultaneously published with the primary results in?The New England Journal of Medicine.
This analysis showed that fewer patients treated with TAGRISSO?in the adjuvant setting had recurrence events or deaths compared to placebo (11% versus 46%). Among patients whose cancer recurred, 38% of those treated with TAGRISSO?had a metastatic recurrence compared to 61% of patients on placebo. TAGRISSO?showed an 82% reduction in the risk of CNS recurrence or death (based on a hazard ratio [HR] of 0.18; 95% confidence interval [CI] 0.10-0.33; p<0.0001). Median CNS DFS was not yet reached in either arm.
In a post-hoc analysis, the estimated probability of observing disease recurrence in the brain at 18 months for patients treated with TAGRISSO?was less than 1% versus 9% for placebo among patients who had not experienced another type of recurrence. On the primary endpoint of DFS in patients with Stage II and IIIA disease, TAGRISSO?in the adjuvant setting reduced the risk of disease recurrence or death by 83% (HR 0.17; 95% CI 0.12-0.23; p<0.0001).
Masahiro Tsuboi, MD, PhD, director of the Department of Thoracic Surgery and Oncology, National Cancer Center Hospital East in Japan, and a principal investigator in the ADAURA Phase III trial, said: ?It?s time to change the notion that treatment for early-stage EGFR-mutated lung cancer ends after surgery, since recurrence rates are still very high even after adjuvant chemotherapy. These new data showing low rates of recurrence, particularly in the brain, combined with the remarkable disease-free survival benefit, clearly demonstrate that TAGRISSO?provides patients with more time living cancer-free.?
Jos? Baselga, Executive Vice President, Oncology R&D, said: ?Once lung cancer has spread to the brain, outcomes are typically devastating for patients. We are now seeing TAGRISSO expanding on its proven efficacy in treating progression in the brain in the metastatic setting as a result of its ability to cross the blood-brain barrier. The striking new data show that TAGRISSO prevents the development of brain metastases in patients with early disease and reinforce that this medicine is truly transformative for patients with EGFR-mutated lung cancer. TAGRISSO should become the standard of care in the adjuvant setting, just as it is for patients with metastatic disease around the world.?
Summary of exploratory results on CNS recurrence in the ADAURA Phase III trial
i. Death in absence of CNS disease recurrence, or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.
ii. Death in the absence of disease recurrence (any site), or death within two visits of baseline where the patient has no evaluable assessments or no baseline data.
The safety and tolerability of TAGRISSO?in this trial was consistent with previous trials in the metastatic EGFRm NSCLC setting. Adverse events at Grade 3 or higher from all causes occurred in 10% of patients in the TAGRISSO?arm versus 3% in the placebo arm as assessed by investigators.
TAGRISSO?is not currently approved in the adjuvant setting in any country.?TAGRISSO?received Breakthrough Therapy Designation in?July 2020?for the adjuvant treatment of patients with early-stage EGFRm NSCLC after complete tumor resection with curative intent. TAGRISSO?is approved for the 1st-line treatment of patients with metastatic EGFRm NSCLC and for the treatment of metastatic EGFR T790M mutation-positive NSCLC in the US, Japan, China, the EU and many other countries around the world.
TAGRISSO IMPORTANT SAFETY INFORMATION
TAGRISSO n=339 |
Placebo n=343 |
|
CNS DFS |
||
HR (95% CI) |
0.18 (0.10-0.33); |
|
p-value |
p<0.0001 |
|
CNS DFS events, patients (%): |
6 (2%) |
39 (11%) |
CNS recurrence |
4 (1%) |
33 (10%) |
Deathi |
2 (1%) |
6 (2%) |
DFS events, patients (%): |
37 (11%) |
159 (46%) |
Type of disease recurrence |
n=37 |
n=157 |
Local/regional only |
23 (62%) |
61 (39%) |
Distant |
14 (38%) |
96 (61%) |
Deathii |
0 |
2 (1%) |
- There are no contraindications for TAGRISSO
- Interstitial lung disease (ILD)/pneumonitis occurred in 3.9% of the 1142 TAGRISSO-treated patients; 0.4% of cases were fatal. Withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (eg, dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
- Heart rate-corrected QT (QTc) interval prolongation occurred in TAGRISSO-treated patients. Of the 1142 TAGRISSO-treated patients in clinical trials, 0.9% were found to have a QTc >500 msec, and 3.6% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
- Cardiomyopathy occurred in 2.6% of the 1142 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) =10% from baseline and to <50% LVEF occurred in 3.9% of 908 patients who had baseline and at least one follow-up LVEF assessment. Conduct cardiac monitoring, including assessment of LVEF at baseline and during treatment, in patients with cardiac risk factors. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
- Keratitis was reported in 0.7% of 1142 patients treated with TAGRISSO in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
- Postmarketing cases consistent with Stevens-Johnson syndrome (SJS) and erythema multiforme major (EMM) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if SJS or EMM is suspected and permanently discontinue if confirmed
- Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose
- Most common adverse reactions (=20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue and decreased appetite
- TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
- TAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy