I am excited to share with you some news for patients with resectable EGFRm NSCLC: Targeted therapy is finally here.1
Adjuvant TAGRISSO was approved with breakthrough therapy designation status as adjuvant therapy after tumor resection in adult patients with 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—this is unparalleled news for resectable EGFRm NSCLC patients.
Disease recurrence is a significant threat in resectable NSCLC:
5-year recurrence or death in resectable NSCLC2
In a separate study, the 2016 IASLC database shows that 5-year survival rates in NSCLC are as follows: stage I, 68-92%; stage II, 53-60%; stage III, 13-36%; stage IV, 0-10%.3
Median DFS was not reached for TAGRISSO (95% CI: 38.8, NE) and was 19.6 months (95% CI: 16.6, 24.5) for control arm.1
Adjuvant TAGRISSO: CNS recurrence in the ADAURA trial§
4 patients treated with adjuvant TAGRISSO had a CNS recurrence and 33 patients in the control arm had a CNS recurrence7
At the time of data cutoff, the total number of patients with events (recurrence or death): 11% (37 of 339 patients) for TAGRISSO and 46% (159 of 343 patients) for placebo
Distant recurrences (either distant only or with locoregional recurrence) were 4% (14 of 339 patients) in the TAGRISSO arm and 28% (96 of 343 patients) in the control arm. Locoregional-only recurrence was observed in 7% (23 of 339 patients) and 18% (61 of 343 patients) in the TAGRISSO and placebo arms, respectively
CNS DFS in ADAURA (post hoc analysis): The hazard ratio indicates an 82% reduced risk of CNS recurrence or death with TAGRISSO¶
HR=0.18 (95% CI: 0.10, 0.33)
6 patients in the TAGRISSO arm experienced CNS recurrence or death and 39 patients in the placebo arm experienced CNS recurrence or death
Exploratory analysis. ||Control arm=placebo
The median CNS DFS was not reached (95% CI: 39.0, NC) in the TAGRISSO arm and was 48.2 months (95% CI: NC, NC) in the placebo group.7
ADAURA study design:
Phase III, double-blind, randomized, placebo-controlled trial in 682 patients with completely resected stage IB, II, and IIIA NSCLC with or without adjuvant chemotherapy. NSCLC patients had centrally confirmed EGFR mutations (exon 19 deletion or L858R mutation). Patients were stratified by stage (IB vs II vs IIIA), EGFR mutation (exon 19 deletion or L858R), and race (Asian vs non-Asian). Patients were randomized to either TAGRISSO (n=339; 80 mg orally, once daily) or placebo (n=343). The maximum interval between surgery and randomization was 26 weeks with adjuvant chemotherapy and 10 weeks without adjuvant chemotherapy. The primary endpoint of the study was DFS by investigator assessment in stage II/IIIA patients. The secondary endpoints were DFS in the overall population (stage
IB/II/IIIA); DFS rates at 2, 3, 4, and 5 years; overall survival (stage II/IIIA and overall population); safety; and health‑related QoL. The planned treatment duration was 3 years or until disease recurrence/unacceptable toxicity.1,4,6
The ADAURA data were released 2 years early, as recommended by an independent data monitoring committee due to overwhelming efficacy. Investigators and patients continue to participate in the trial and remain blinded to treatment.4
SELECT SAFETY INFORMATION
There are no contraindications for TAGRISSO
TAGRISSO is associated with several serious and sometimes fatal adverse reactions, including interstitial lung disease (ILD)/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, erythema multiforme and Stevens-Johnson syndrome, cutaneous vasculitis, and embryo-fetal toxicity
The most common (≥20%) adverse reactions, including lab abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough
Please see full Important Safety Information below and complete Prescribing Information, including Patient Information.
In patients with resectable NSCLC, REFER every resected NSCLC patient to a medical oncologist, TEST every surgical specimen for EGFR mutations, CHOOSE adjuvant TAGRISSO for every eligible patient1
TAGRISSO: Convenient, once-daily dosing1
Treat patients in the adjuvant setting until disease recurrence, or unacceptable toxicity, or for up to 3 years.1#
In the ADAURA trial, patients are treated for 3 years or until disease recurrence or unacceptable toxicity.1
If a dose of TAGRISSO is missed, do not make up the missed dose and take the next dose as scheduled.1
Select patients for treatment with TAGRISSO based on the presence of EGFR exon 19 deletions or exon 21 L858R mutations.
IMPORTANT SAFETY INFORMATION
There are no contraindications for TAGRISSO
Interstitial lung disease (ILD)/pneumonitis occurred in 3.7% of the 1479 TAGRISSO‑treated patients; 0.3% 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 1479 TAGRISSO-treated patients in clinical trials, 0.8% were found to have a QTc >500 msec, and 3.1% 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 3% of the 1479 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 3.2% of 1233 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. 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 1479 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
Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
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 (≥20%) adverse reactions, including laboratory abnormalities, were leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, and cough
TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with 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
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References:1. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020. 2. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung Adjuvant Cisplatin Evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552‑3559. 3. Goldstraw P, Chansky K, Crowley J, et al; IASLC. The IASLC Lung Cancer Staging Project: proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. J Thorac Oncol. 2016;11(1):39‑51. 4. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR‑mutated non‑small‑cell lung cancer [published online ahead of print September 19, 2020].
N Engl J Med. doi:10.1056/NEJMoa2027071. 5. DoFP REF‑98491. AstraZeneca Pharmaceuticals LP. 6. DoFP. REF-98825. AstraZeneca Pharmaceuticals LP. 7. Wu YL, Tsuboi M, He J, et al; ADAURA Investigators. Osimertinib in resected EGFR‑mutated
non‑small‑cell lung cancer. N Engl J Med. 2020;383(18):1711-1723.
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