Pemetrexed Dipotassium

WILMINGTON, Del.--(BUSINESS WIRE)--Positive high-level results from the final overall survival (OS) analysis of the FLAURA2 Phase III trial showed AstraZeneca’s TAGRISSO® (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS compared to TAGRISSO monotherapy for patients with 1st-line locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).​ The final OS analysis demonstrates consistent survival benefit previously reported in the interim OS results, and builds on the previously presented primary endpoint data, which demonstrated the longest-reported median progression-free survival (PFS) in this setting. Pasi A. Jänne, MD, PhD, Senior Vice President for Translational Medicine and thoracic medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: “When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in 1st-line where treatment duration can be long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with 1st-line advanced EGFR-mutated lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “These exciting overall survival results add to the extensive evidence supporting TAGRISSO as the backbone therapy in EGFR-mutated lung cancer, demonstrating that TAGRISSO plus chemotherapy can significantly extend survival in the 1st-line advanced setting, in addition to prior trials showing survival benefits as monotherapy in both early stage and advanced disease. With its strong survival benefit and tolerable safety profile, this combination has the potential to help patients live longer while maintaining their quality of life on treatment.” With longer follow up, the safety profile of TAGRISSO plus chemotherapy continues to be manageable and consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the TAGRISSO plus chemotherapy arm, driven by well-characterized chemotherapy-related AEs. Discontinuation rates due to AEs and on-target toxicities were low in both arms of the trial. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. TAGRISSO plus chemotherapy is approved in more than 80 countries, including the US, EU, China and Japan, based on the FLAURA2 Phase III trial. IMPORTANT SAFETY INFORMATION There are no contraindications for TAGRISSO TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy: ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT): For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. 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 TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 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%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. 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 0.6% of 1813 patients treated with TAGRISSO monotherapy 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 erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN 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 TAGRISSO-treated patients in clinical trials (0.06% of 1813) 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 last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose Most common (≥20%) adverse reactions, including laboratory abnormalities, were: 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 treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and 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 in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic 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 epidermal growth factor receptor (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. Notes NSCLC Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for 80-85% of cases.1-2 Approximately 75% of people are diagnosed with advanced NSCLC.3 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.4-6 While EGFR-tyrosine kinase inhibitors (TKI) have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.7-10 FLAURA2 FLAURA2 is a randomized, open-label, multi-center, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO 80mg QD oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by TAGRISSO with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centers across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS with OS as the key secondary endpoint. TAGRISSO TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. TAGRISSO (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC. TAGRISSO is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy (CRT). TAGRISSO plus chemotherapy is approved in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC. There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC. TAGRISSO is the only targeted therapy shown to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including TAGRISSO and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca. References World Health Organization. International Agency for Research on Cancer. Lung Cancer Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed July 2025. American Cancer Society. What Is Lung Cancer?. https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html . Accessed July 2025. Chen HJ, et al. Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI. Medicine . 2021;100(6):e24688. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol . 2011:29;2121-27. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol . 2013;6:2800-2812. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol . 2013;66:79-89. Chen R, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol . 2020;13(1):58. Majeed U, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol . 2021;14(1):108. Morgillo F, et al. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open . 2016;1(3):e000060. Han B, et al. Efficacy of pemetrexed-based regimens in advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations after tyrosine kinase inhibitor failure: a systematic review. Onco Targets Ther . 2018;11:2121-2129.

Longer-term follow up in the FLAURA2 Phase III trial confirms the favourable benefit-risk profile of this combination Overall survival results reinforce Tagrisso as the backbone therapy in EGFRm lung cancer across stages LONDON, UK I July 21, 2025 I Positive high-level results from the final overall survival (OS) analysis of the FLAURA2 Phase III trial showed AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS compared to Tagrisso monotherapy for patients with 1st-line locally advanced or metastatic epidermal growth factor receptor-mutated ( EGFR m) non-small cell lung cancer (NSCLC).​ The final OS analysis demonstrates consistent survival benefit as previously reported in the interim OS results , and builds on the previously presented primary endpoint data , which demonstrated the longest-reported median progression-free survival (PFS) in this setting. Pasi A. Jänne, MD, PhD, Senior Vice President for Translational Medicine and thoracic medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: “When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in 1st-line where treatment duration can be long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with 1st-line advanced EGFR -mutated lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “These exciting overall survival results add to the extensive evidence supporting Tagrisso as the backbone therapy in EGFR -mutated lung cancer, demonstrating that Tagrisso plus chemotherapy can significantly extend survival in the 1st-line advanced setting, in addition to prior trials showing survival benefits as monotherapy in both early stage and advanced disease. With its strong survival benefit and tolerable safety profile, this combination has the potential to help patients live longer while maintaining their quality of life on treatment.” With longer follow up, the safety profile of Tagrisso plus chemotherapy continues to be manageable and consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Discontinuation rates due to AEs and on-target toxicities were low in both arms of the trial. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Tagrisso plus chemotherapy is approved in more than 80 countries, including the US, EU, China and Japan, based on the FLAURA2 Phase III trial. Notes NSCLC Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths. 1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for 80-85% of cases. 1-2 Approximately 75% of people are diagnosed with advanced NSCLC. 3 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFR m NSCLC. 4-6 While EGFR- tyrosine kinase inhibitors (TKI) have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options. 7-10 FLAURA2 FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFR m NSCLC. Patients were treated with Tagrisso 80mg QD oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS with OS as the key secondary endpoint. Tagrisso Tagrisso (osimertinib) is a third-generation, irreversible EGFR -TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Tagrisso (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFR m NSCLC. Tagrisso is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFR m NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFR m NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy (CRT). Tagrisso plus chemotherapy is approved in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFR m NSCLC. There is an extensive body of evidence supporting the use of Tagrisso in EGFR m NSCLC. Tagrisso is the only targeted therapy shown to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca . References 1. World Health Organization. International Agency for Research on Cancer. Lung Cancer Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed July 2025. 2. American Cancer Society. What Is Lung Cancer?. https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed July 2025. 3. Chen HJ, et al. Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI. Medicine . 2021;100(6):e24688. 4. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol . 2011:29;2121-27. 5. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol . 2013;6:2800-2812. 6. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol . 2013;66:79-89. 7. Chen R, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol . 2020;13(1):58. 8. Majeed U, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol . 2021;14(1):108. 9. Morgillo F, et al. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open . 2016;1(3):e000060. 10. Han B, et al. Efficacy of pemetrexed-based regimens in advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations after tyrosine kinase inhibitor failure: a systematic review. Onco Targets Ther . 2018;11:2121-2129. SOURCE: AstraZeneca