EGFR-mutated Metastatic Non-small Cell Lung Research Articles

Treatment Patterns, Clinical Outcomes and Health Care Resource Utilisation in Patients with EGFR-mutated Metastatic Non-Small Cell Lung Cancer: A Real-World Study in South Korea.

Despite the dynamic treatment landscape for EGFR mutant-positive metastatic non-small cell lung cancer (EGFRm+ mNSCLC), most of the earlier studies have focused on US or Western populations. The objective of this study was to explore real-world treatment patterns and outcomes of South Korean patients with EGFRm+ mNSCLC. Retrospective chart review of adult patients with EGFRm+ mNSCLC who received systemic treatment between January-2019 and June-2019. A total of 162 patients were included from 21 hospitals, with a median follow-up of 15.6 months. Median age was 65.0 years, 22% had central nervous system metastasis, and 57% and 38% had exon 19 deletion and exon 21 L858R, respectively. Among 144 patients (89%) who received first-line EGFR-tyrosine kinase inhibitor, afatinib was most the common (44%), followed by gefitinib (28%) and erlotinib (13%). First-line chemotherapy was more common when an EGFR-mutation was detected after versus before first-line treatment initiation (31% vs 5%). Discontinuation of first-line treatment was mostly due to disease-progression (81%) and toxicity (7%). Among 58 (78%) patients who received second-line treatment, osimertinib was the most common (40%). Most (60%) patients reported ≥1 Grade ≥3 adverse event during first-line treatment. Following initiation of first-line treatment, physician visits and chest X-rays were the most frequent healthcare utilisation events. Rates of emergency-room visits and hospitalization were 12% and 16%, respectively, with a mean length-of-stay of 10.4 days. At 12 months, overall survival rate was 95%, and numerically worse for patients with exon 21 versus 19 mutations. Characteristics and clinical outcomes of Korean patients with EGFRm+ mNSCLC in real-world practice were comparable to those observed in clinical trials. As osimertinib was not reimbursed for first-line treatment before study completion, further investigation is warranted to explore evolving treatment practice.

Neoadjuvant targeted therapy for resectable EGFR-mutant non-small cell lung cancer: Current status and future considerations.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) targeted therapy has become the standard of care for patients with EGFR-mutated metastatic non-small cell lung cancer (NSCLC) on the basis of improved prognosis and reduced toxicities compared with chemotherapy. In view of the therapeutic potential of EGFR-TKIs in EGFR-mutated advanced NSCLC, several scholars have explored the value of preoperative use of EGFR-TKIs in patients with EGFR-mutated resectable NSCLC. However, the field of neoadjuvant targeted therapy for EGFR-mutated resectable NSCLC is currently in its infancy. In this mini-review, we summarize the current evidence on neoadjuvant EGFR-TKIs targeted therapy for resectable EGFR-mutated NSCLC and focus on discussing potential clinical strategies of treating resectable EGFR-mutated patients by preoperative administration of EGFR-TKIs-based multimodality therapy.

LBA8 Nivolumab (NIVO) + chemotherapy (chemo) vs chemo in patients (pts) with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) with disease progression after EGFR tyrosine kinase inhibitors (TKIs) in CheckMate 722

Treatment (tx) options are limited for pts with EGFR-mutated (mut) mNSCLC who experience disease progression following EGFR TKIs. CheckMate 722 (NCT02864251) is a randomized, open-label, phase 3 study of NIVO + chemo vs chemo in pts with EGFR-mut mNSCLC after progression on EGFR TKIs.

MA07.05 Phase 1b/2 Study of Combined HER Inhibition in Refractory EGFR-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)

Patients with metastatic EGFR-mutated NSCLC who have progressed on osimertinib have limited treatment options. Dual EGFR blockade with HER2 blockade has been shown to have complete and long-term reversal of osimertinib resistance in preclinical models.

CTNI-46. PHASE I OPEN-LABEL, SINGLE-CENTER, DOSE ESCALATION STUDY (NCT02423525) OF PULSATILE AFATINIB IN PATIENTS WITH BRAIN CANCER

Abstract Afatinib is a small molecule, selective and irreversible ErbB family blocker. In preclinical models it effectively inhibits EGFR, HER2 and HER4 phosphorylation resulting in tumor growth inhibition and is approved for the treatment of EGFR-mutated metastatic non-small cell lung carcinoma and metastatic squamous cell lung carcinoma. Pulse dosing afatinib could potentially increase CNS exposure to reach therapeutic levels while allowing a recovery period to mitigate toxicities. We are reporting the results of a Phase I open-label, single-center, ‘3 + 3’ dose escalation study to determine the safety and tolerability of pulsatile Afatinib in patients with brain cancer and to define a recommended phase 2 dose. The study assessed the exposure of Afatinib in cerebrospinal fluid and serum, objective tumor response according to RANO criteria, progression-free survival, and overall survival, and will explore the association between molecular phenotypes and patient response. In total, 26 patients were screened and 24 were enrolled (median age 60, 78% male, 87.5% Caucasian, glioblastoma N=16, chordoma N=3, brain metastases N=2, meningioma N=1, anaplastic mixed oligoastrocytoma N=1). Patients had received a median of 2.5 prior treatments. The study proceeded through the 4 dosing cohorts without reaching dose-limiting toxicity: Cohort 1 (80mg every 4 days) N=3; Cohort 2 (120mg every 4 days) N=3; Cohort 3 (180mg every 4 days) N=7, including replacement patients; Cohort 4 (280mg every 7 days) N=11. Diarrhea (75%), rash (75%), nausea/vomiting (37.5%), fatigue (29.2%), anorexia (25%), and limb edema (16.7%) were the most common side effects. There were no CTCAE defined grade 4 toxicities. Grade 3 side effects infrequently occurred in the highest dosing cohort and once in each cohort 2 and 3. These results demonstrate that pulsatile Afatinib at a dose of 280mg every 7 days is safe and tolerable for patients with brain involving cancers.

Cost-effectiveness analysis of adding ramucirumab to the first-line erlotinib treatment for untreated EGFR-mutated metastatic non-small cell lung cancer in China

ObjectiveTo investigate the cost-effectiveness of ramucirumab plus erlotinib compared with placebo plus erlotinib in the first-line setting for patients with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) from the Chinese...

1397P High incidence of treatment-related adverse events after combination EGFR tyrosine-kinase inhibitor and immune checkpoint inhibitors in EGFR-mutated metastatic non-small cell lung cancer: A systematic review and meta-analysis

1397P High incidence of treatment-related adverse events after combination EGFR tyrosine-kinase inhibitor and immune checkpoint inhibitors in EGFR-mutated metastatic non-small cell lung cancer: A systematic review and meta-analysis

Nivolumab + chemotherapy vs chemotherapy in EGFR-mutated NSCLC after 1L or 2L EGFR-TKIs (CheckMate 722)

Abstract Background Although osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI) is approved for first-line (1L) treatment of EGFR-mutated metastatic non-small cell lung cancer (NSCLC) and second-line (2L) treatment of pts who acquired the EGFR T790M mutation during 1L therapy with other TKIs, treatment options after progression on TKIs are limited; platinum-doublet chemotherapy (PT-DC) remains the standard therapy, including for pts with no T790M mutation. Nivolumab (NIVO), a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, is approved worldwide for the treatment of advanced NSCLC on or after prior chemotherapy. CheckMate 722 (NCT02864251) will compare the efficacy and safety of NIVO + PT-DC vs PT-DC alone in pts with EGFR-mutated metastatic or recurrent NSCLC progressed on 1L or 2L EGFR TKI therapy. Methods This open-label phase 3 trial is enrolling ∼500 adults with confirmed stage IV or recurrent EGFR-mutated NSCLC progressed on prior EGFR TKI therapy. Patients are eligible if they progressed on 1L first- or second-generation TKIs with no T790M mutation or 1L or 2L osimertinib regardless of T790M status. Pts with CNS metastases that are adequately controlled and/or treated during screening are eligible. Pts are randomized 1:1 to NIVO (360 mg Q3W) + PT-DC (pemetrexed 500 mg/m2 Q3W + cisplatin 75 mg/m2 or carboplatin AUC 5 or 6 Q3W), or PT-DC alone; pts without disease progression after 4 cycles will receive NIVO + pemetrexed or pemetrexed, respectively, until disease progression or unacceptable toxicity. Randomization is stratified by programmed death ligand-1 status (≥ 1% or Results The estimated primary completion date is September 2019.

Dacomitinib for the first-line treatment of patients with EGFR-mutated metastatic non-small cell lung cancer

ABSTRACTIntroduction: Different EGFR tyrosine kinase inhibitors (TKIs) are currently approved for the first-line treatment of NSCLC patients with EGFR mutations. Dacomitinib is an orally administered, second-generation pan-HER inhibitor that has shown to improve PFS and OS compared to the first-generation TKI gefitinib and is the most recent inhibitor to be approved in this setting.Areas covered: This article will review relevant literature regarding preclinical findings and clinical data from phase I-III trials of dacomitinib. We particularly discuss the mechanism of action of dacomitinib and its clinical efficacy and toxicity as a novel, first-line therapeutic option for EGFR-mutated NSCLC.Expert commentary: The therapeutic landscape for EGFR-mutated NSCLC has been greatly expanded. In the first-line setting, we have currently first-, second- and third-generation EGFR TKIs available and some combination strategies, including EGFR TKIs with anti-angiogenic drugs or chemotherapy, have also shown to be effective. However, more data are needed to define the optimal therapeutic sequencing of all these targeted agents and combinations. In this view, molecular profiling of tumor tissues and liquid biopsies may provide novel insights on mechanisms of resistance to different drugs and guide treatment decisions.

Clinical benefit of EGFR-TKIs plus radiotherapy for treating EGFR-mutated metastatic non-small cell lung cancer.

e20694 Background: Despite the high response rate and prolonged OS of patients with EGFR mutations treated with gefitinib or erlotinib, there are still major clinical obstacles. The local control rate is still low, only 19.4%–58%, with first-line treatment using EGFR-targeted therapy. The aim of this study is to provide scientific evidence to support the clinical benefits of EGFR-TKI combined with radiotherapy compared to EGFR-TKI alone. Methods: From February 2015 to May 2017, a total of 103 patients with stage IV EGFR-mutated NSCLC treated at Sichuan Cancer Hospital & Institute were analysed retrospectively. 50 patients were treated with EGFR-TKIs (gefitinib or erlotinib) plus radiotherapy (Group TKI-RT) and 53 patients received EGFR-TKIs alone (Group TKI). Tumour response, survival and toxicities were compared between the two groups. Results: Median follow up time was 11.7 months (range: 2.8–36.3 months). The overall response rate (ORR) and disease control rate (DCR) in Group TKI-RT vs. Group TKI were 62% vs. 37.7% (P = 0.014) and 88% vs. 75.5% (P = 0.101), respectively. The median progression-free survival (PFS) and median overall survival (OS) in Group TKI-RT were superior to those of Group TKI (18.87 months vs. 12.80 months, P = 0.035 and 23.10 months vs. 18.30 months, P = 0.011). OS rates in Group TKI-RT and Group TKI were 56.0% vs. 35.8% at 1-year (P = 0.04) and 16.0% vs. 3.8% at 2-year (P = 0.036). Multivariate Cox model found that TKI-RT related to significantly better OS (hazard ratio = 0.209; 95% CI, 0.066 to 0.661; P = 0.008) than TKI alone. Adverse events did not differ significantly between the two groups. Conclusions: Compared with EGFR-TKIs alone, EGFR-TKIs combined with radiotherapy was well tolerated and showed benefit in tumour response and survival for EGFR mutation-positive metastatic NSCLC patients.

P2.03-043 A Phase 1b Study of Erlotinib and Momelotinib for TKI-Naïve EGFR-Mutated Metastatic Non-Small Cell Lung Cancer

P2.03-043 A Phase 1b Study of Erlotinib and Momelotinib for TKI-Naïve EGFR-Mutated Metastatic Non-Small Cell Lung Cancer