Metastatic Non-Small Cell Lung Cancer (mNSCLC) patients: The importance of targeted therapies

Despite a steady decrease in incidence, lung cancer remains the leading cause of cancer-related deaths in the United States.¹ In fact, more than half of people with metastatic lung cancer will die within one year of diagnosis.² Due to the disease’s sometimes non-existent early-stage symptoms, detection is historically delayed.¹

Of all lung cancer patients, approximately 80 to 85% are categorized as having non-small cell lung cancer (NSCLC),³ and within this majority, 30-40% present with metastatic disease, ⁴ which has the lowest survival rate (8%).⁵ Because metastatic NSCLC (mNSCLC) is not a single disease, understanding each patient’s drivers of disease is particularly important. The identification of an actionable driver mutation can help determine appropriate treatment options — and in certain cases, influence outcomes.⁶

The importance of biomarker testing and confirming mutational status

Current treatment guidelines recommend that mNSCLC patients should be tested for actionable mutations to help guide appropriate first-line treatment options.⁷

For example, approximately 20 percent of patients with mNSCLC of the adenocarcinoma subtype have a sensitizing epidermal growth factor receptor (EGFR) mutation, including EGFR exon 19 deletion and exon 21 L858R mutation.⁸ This biomarker indicates that the appropriate option for this patient may be a targeted therapy that may help extend progression-free survival or overall survival.⁹

“Regardless of clinicopathologic features — such as smoking history, race or gender — any patient with NSCLC may have an actionable driver mutation like EGFR.¹⁰ When biomarker testing occurs, the results can help inform a medical oncologist’s next steps in targeting the cancer’s growth and spread through appropriate precision-oriented treatment,” continued Dr Husain.

Groundbreaking progression-free survival with TAGRISSO® (osimertinib)

For patients with EGFRm mNSCLC specifically, results from TAGRISSO® (osimertinib) studies have shown overwhelming evidence of its efficacy as a first-line treatment.

TAGRISSO is an oral tyrosine kinase inhibitor (TKI) that is FDA approved as a first-line treatment option for adult patients with mNSCLC with certain EGFR mutations (exon 19 deletions or exon 21 L858R mutations).

FLAURA was a global Phase III study in patients with metastatic EGFRm NSCLC. The primary endpoint was progression-free survival – which is a direct measure of first-line efficacy. The median PFS was nearly doubled (18.9 months with TAGRISSO vs 10.2 months with the EGFR-TKI comparator, erlotinib/gefitinib [HR=0.46 (95% CI: 0.37-0.57), P<0.0001]).¹¹ There was a 54% reduction in the relative risk of progression or death vs erlotinib or gefitinib.¹²

TAGRISSO demonstrated significant overall survival beyond 3 years

Groundbreaking results from the TAGRISSO FLAURA study also demonstrated statistically significant median overall survival (OS) beyond three years, extending OS by nearly seven months compared to EGFR-TKI comparator, erlotinib or gefitinib (38.6 months with TAGRISSO versus 31.8 months with erlotinib or gefitinib [hazard ratio=0.80 (95% CI: 0.64-1.00), P=0.0462; secondary endpoint]).¹¹

Clinical trial data have reinforced the efficacy of TAGRISSO as a first-line treatment in the metastatic NSCLC setting with specific EGFR biomarkers.¹¹ However, for patients to be eligible for this treatment, it is critical that care teams prioritize biomarker testing and the identification of disease drivers.

Beyond its indication for metastatic EGFRm NSCLC, TAGRISSO is also FDA approved as an adjuvant treatment after tumor resection in patients with resectable EGFRm NSCLC with certain mutations (exon 19 deletion or exon 21 L858R mutation).¹¹

“It’s hard to overstate the importance of biomarker testing in understanding non-small cell lung cancer at the molecular level. The knowledge is not only vital for the care team, but also for the patient and family weighing their treatment options,” states Dr Husain. “This information helps to determine a patient’s treatment journey.”

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 occurs 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
• Aplastic anemia has been reported in patients treated with TAGRISSO in clinical trials (0.07% of 1479) and postmarketing. Some cases had a fatal outcome.  Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor.  If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO.  Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
• 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

INDICATIONS

• 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
• TAGRISSO is indicated for the first-line treatment of adult 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 adult 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

Please see complete Prescribing Information, including Patient Information for TAGRISSO.

You may report side effects related to AstraZeneca products by clicking here.

CI, confidence interval; DFS, disease-free survival; EGFRm, epidermal growth factor receptor mutation positive; HR, hazard ratio; NE, not estimable; NSCLC, non-small cell lung cancer; OS, overall survival; PFS, progression-free survival.

References

1. American Cancer Society (ACS). Cancer facts & figures 2022. Atlanta, GA: American Cancer Society; 2022. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2022/2022-cancer-facts-and-figures.pdf. Accessed January 24, 2023.
2. U.S. National Institute of Health, National Cancer Institute. SEER Cancer Statistics Review, 1975–2015.
3. American Cancer Society (ACS). What Is Lung Cancer? Atlanta, GA: American Cancer Society; 2017. https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed January 24, 2023.
4. Tamura T, Kurishima K, Nakazawa K, et al. Specific organ metastases and survival in metastatic non-small-cell lung cancer. Mol Clin Oncol. 2015;3(1):217-221. doi:10.3892/mco.2014.410.
5. Lung cancer survival rates. American Cancer Society. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/survival-rates.html. Accessed January 24, 2023.
6. Mack PC, Banks KC, Espenschied CR, et al. Spectrum of driver mutations and clinical impact of circulating tumor DNA analysis in non-small cell lung cancer: Analysis of over 8000 cases. Cancer. 2020;126(14):3219-3228. doi:10.1002/cncr.32876.
7. Hanna NH, Robinson AG, Temin S, et al. Therapy for stage IV non-small-cell lung cancer with driver alterations: ASCO and OH (CCO) joint guideline update. J Clin Oncol. 2021;39(9):1040-1091.
8. Jordan EJ, Kim HR, Arcila ME, et al. Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies. Cancer Discov. 2017;7(6):596-609.
9. Guo H, Zhang J, Qin C, et al. Biomarker-Targeted Therapies in Non-Small Cell Lung Cancer: Current Status and Perspectives. Cells. 2022;11(20):3200. Published 2022 Oct 12. doi:10.3390/cells11203200
10. Data on File, US-42770, AstraZeneca Pharmaceuticals LP.
11. TAGRISSO [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2022.
12. Scott LJ. Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Drugs Ther Perspect. 2018;34(8):351-357. doi:10.1007/s40267- 018-0536-9.