Advanced EGFR Mutation-positive Non-small Cell Research Articles

Real-world first-line afatinib for advanced EGFR mutation-positive non-small cell lung cancer in Korea: updated survival data

Real-world first-line afatinib for advanced EGFR mutation-positive non-small cell lung cancer in Korea: updated survival data

Efficacy and safety of icotinib in the treatment of advanced EGFR mutation-positive nonsmall cell lung cancer: A meta-analysis of randomized controlled trials

Icotinib is the first generation of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) independently developed in China, which has been widely used in the treatment of advanced EGFR mutation-positive nonsmall cell lung cancer (NSCLC). The purpose of this study was to systematically evaluate the efficacy and safety of icotinib in the treatment of advanced EGFR mutation-positive NSCLC and to provide evidence-based evidence for clinical rational drug use. Up to September 30, 2022, the databases of PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, China National Knowledge Infrastructure, and Wanfang were searched, and the randomized controlled trials (RCTs) of icotinib (experimental group) versus gefitinib or erlotinib (control group) in the treatment of EGFR-positive advanced NSCLC were included. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included literature. Revman5.4 software was used for meta-analysis. A total of 957 patients were included in 12 studies. The results of meta-analysis showed that the objective response rate (ORR) and disease control rate (DCR) of the experimental group were better than those of the control group (relative risk (RR) = 1.29, 95% confidence interval (CI): 1.10-1.50, P = .001; RR = 1.10, 95%CI: 1.02-1.18, P = .01). There was no significant difference in progression-free survival (PFS) and overall survival between the 2 groups (P > .05). The results of stratified analysis showed that icotinib significantly improved the ORR of EGFR-positive advanced NSCLC patients compared with gefitinib (RR = 1.20, 95%CI: 1.01-1.43, P = .03), but had no significant improvement in DCR (RR = 1.08, 95%CI: 0.99-1.16, P = .07). Compared with erlotinib, icotinib significantly improved ORR and DCR (RR = 1.69, 95%CI: 1.17-2.45, P = .005; RR = 1.21, 95%CI: 1.01-1.44, P = .04). In terms of adverse events of drugs, the incidence of nausea and vomiting in the experimental group was significantly lower than that in the control group (P < .05). Icotinib is safer than gefitinib or erlotinib in the treatment of advanced EGFR-positive NSCLC and seems to bring more clinical benefits to patients. However, there is no obvious advantage in improving the survival rate of patients, and long-term follow-up clinical studies are needed to verify its efficacy.

Network Meta Analysis of the Efficacy and Safety of the First-line Treatment Regimen for Advanced EGFR Mutation-positive Non-small Cell Lung Cancer

Network Meta Analysis of the Efficacy and Safety of the First-line Treatment Regimen for Advanced EGFR Mutation-positive Non-small Cell Lung Cancer

Real-world experience of afatinib as first-line therapy for advanced EGFR mutation-positive non-small cell lung cancer in Korea.

BackgroundWe investigated the clinical characteristics and treatment outcomes of Korean patients receiving first-line afatinib for advanced epidermal growth factor receptor mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) in a real-world setting.MethodsElectronic case reports were retrospectively reviewed from patients across 15 sites in South Korea. Outcome measures included baseline characteristics, overall response rate (ORR), time-to-treatment discontinuation (TTD), and overall survival (OS). Subgroups were: presence/absence of brain metastases at baseline, dose reductions, and baseline EGFR mutation category.ResultsAmong 422 patients, 39.8% had brain metastases and 59.0%/25.1%/10.0%/5.0% had Del19/L858R/compound/uncommon EGFR mutations at baseline. ORR was 62.6% overall; responses were observed across all EGFR mutation categories, including against compound mutations. Median TTD was 17.8 months; median OS was not reached (NR). Median TTD and OS were longer in patients without versus with brain metastases (TTD: 22.9 vs. 14.8 months, P=0.001; OS: NR vs. 40.3 months, P=0.0009) and patients with versus without dose reductions (TTD: 22.2 vs. 14.2 months, P=0.0004; OS: NR vs. 40.3 months, P=0.0117). Median OS was 30.5/37.7 months in patients receiving chemotherapy/osimertinib as subsequent therapy. The most common treatment-related adverse events (TRAEs; any grade/grade ≥3) were diarrhea (31.3%/8.5%) and rash (23.0%/8.1%). Overall, 34 patients (8.1%) discontinued afatinib due to AEs.ConclusionsAfatinib was well tolerated with no new safety signals, and efficacy was encouraging in Korean patients with EGFRm+ NSCLC, including those with baseline brain metastases and/or uncommon EGFR mutations. AE management with dose reductions facilitated a long TTD, prolonging the chemotherapy-free period for many patients.

P76.69 Real-World Effectiveness of EGFR TKI First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in US

P76.69 Real-World Effectiveness of EGFR TKI First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in US

Second-line treatment of EGFR T790M-negative non-small cell lung cancer patients.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the currently recommended treatment for advanced EGFR mutation-positive non-small cell lung cancer (NSCLC). Acquired resistance inevitably develops, with the EGFR T790M mutation comprising approximately 55% of the mechanisms of resistance following first- or second-generation EGFR-TKI therapy (e.g. gefitinib, erlotinib, afatinib, and dacomitinib). Patients without T790M are a heterogeneous group for whom platinum-based chemotherapy is currently recommended as a second-line treatment. In addition to secondary mutations in EGFR (e.g. T790M), the currently known resistance mechanisms can be classified into the following three categories: bypass pathways, downstream signaling pathways, and histologic transformations. Given the evolving knowledge and convenience of diagnosing acquired resistance mechanisms by next-generation sequencing and liquid biopsy, exploratory studies targeting these resistance mechanisms and incorporating immunotherapy into the treatment paradigm have become the mainstream of future development. This review focuses on acquired resistance mechanisms other than T790M that develop after first- or second-generation EGFR-TKI therapy. Exploratory second-line treatments targeting resistance mechanisms as well as combination immunotherapy and chemotherapy in ongoing clinical trials are reviewed here. We also highlight the recent development of next-generation sequencing and liquid biopsy in this field.

Recherche de la mutation T790 M : savoir persévérer

In cases of advanced EGFR mutation-positive non-small cell lung cancer, first or second generation EGFR-tyrosine kinase inhibitors (TKI-EGFR 1G or TKI-EGFR 2G) are recommended as first line treatment. Inexorably, progressive disease occurs and, in 50-60% of the cases, is secondary to a T790M resistant mutation. The prescription of osimertinib (TKI-EGFR3G) in second line is dependent on identification of the T790M mutation. We report 7 cases in which the identification of the T790M mutation required repeated analyses of cell free DNA and/or biopsies over a period of time. In some cases, a positive result was obtained a long time after progressive disease had been diagnosed during treatment with first or second generation EGFR-TKI. We discuss here the different modalities of screening for the T790M mutation and we encourage persevering in this search when no alternative mechanism of resistance has been identified.

Update on recent preclinical and clinical studies of T790M mutant-specific irreversible epidermal growth factor receptor tyrosine kinase inhibitors.

The first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (1/2G EGFR-TKIs) gefitinib, erlotinib, and afatinib have all been approved as standard first-line treatments for advanced EGFR mutation-positive non-small cell lung cancer. The third-generation (3G) EGFR-TKIs have been developed to overcome the EGFR T790M mutation, which is the most common mechanism of acquired resistance to 1/2G EGFR-TKI treatment. This resistance mutation develops in half of the patients who respond to 1/2G EGFR-TKI therapy. The structures of the novel 3G EGFR-TKIs are different from those of 1/2G EGFR-TKIs. Particularly, 3G EGFR-TKIs have lower affinity to wild-type EGFR, and are therefore associated with lower rates of skin and gastrointestinal toxicities. However, many of the adverse events (AEs) that are observed in patients receiving 3G EGFR-TKIs have not been observed in patients receiving 1/2G EGFR-TKIs. Although preclinical studies have revealed many possible mechanisms for these AEs, the causes of some AEs remain unknown. Many mechanisms of resistance to 3G EGFR-TKI therapy have also been reported. Here, we have reviewed the recent clinical and preclinical developments related to novel 3G EGFR-TKIs, including osimertinib, rociletinib, olmutinib, EGF816, and ASP8273.

A potential new therapeutic option for patients with advanced EGFR mutation-positive non-small cell lung cancer in first-line setting.

EGFR mutation-positive non-small cell lung cancer (NSCLC) is a well-defined molecular subtype of lung cancer. We already know data on frequency and characteristics of EGFR mutations among patients with NSCLC and their response to tyrosine kinase inhibitors (TKIs) (1). Actually these small molecules represent the standard first-line treatments for this setting of patients, while platinum-based doublet chemotherapy is the standard first-line treatment for patients with wild type EGFR NSCLC (2).

PCN51 - Budget Impact Analysis of Erlotib as the First-Line Therapy of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in Vietnam

PCN51 - Budget Impact Analysis of Erlotib as the First-Line Therapy of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in Vietnam

PCN115 - Cost-Utility Analysis of Erlotib Versus Standard Chemotherapy in First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in Vietnam

PCN115 - Cost-Utility Analysis of Erlotib Versus Standard Chemotherapy in First-Line Treatment of Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer in Vietnam

138PD Impact of dose adjustment on the safety and efficacy of afatinib in patients (pts) with advanced EGFR mutation-positive non-small cell lung cancer (NSCLC): Post-hoc analyses of LUX-Lung 3 (LL3) and LUX-Lung 6 (LL6)

Background Afatinib 40 mg/day is approved for the first-line treatment of pts with EGFR mutation-positive NSCLC. The dose can be adjusted based on individual tolerability. Post-hoc analyses assessed the impact of afatinib dose adjustment on adverse events (AEs), pharmacokinetics (PK) and progression-free survival (PFS) in LL3 and LL6. Methods All afatinib-treated pts in LL3 (n = 229) and LL6 (n= 239) were included. In case of drug-related grade 3 or selected prolonged grade 2 AEs with afatinib 40 mg, the dose could be reduced by 10 mg decrements to a minimum of 20 mg. We analysed the incidence and severity of common AEs before and after dose reduction and compared PK data collected as part of the standard visit schedule on Day 43 in pts who reduced to 30 mg vs those remaining at 40 mg. PFS in pts who dose reduced within the first 6 months of treatment was compared with those who remained on afatinib 40 mg/day. Results Dose reductions occurred in 53% (122/229) and 28% (67/239) of pts in LL3 and LL6, respectively; the majority (86% and 82%, respectively) within the first 6 months of treatment. Dose reduction led to decreases in the incidence and severity of EGFR-mediated drug-related AEs (table). Combined PK analysis of LL3 and LL6 suggested that dose reduction was more likely in pts with higher plasma concentrations of afatinib. On Day 43, pts who had dose reduced to 30 mg (n = 59) had geometric mean plasma afatinib concentrations of 23.3 ng/mL, vs 22.8 ng/mL in pts who remained on the 40 mg dose (n = 284). Median PFS was similar in pts who dose reduced during the first 6 months of treatment vs those who did not in LL3 (11.3 vs 11.0 months [HR = 1.25; 95% CI, 0.91–1.72]) and LL6 (12.3 vs 11.0 months [HR = 1.00; 95% CI, 0.69–1.46]).

Gene-guided Gefitinib switch maintenance therapy for patients with advanced EGFR mutation-positive Non-small cell lung cancer: an economic analysis

BackgroundMaintenance therapy with gefitinib notably improves survival in patients with advanced non-small cell lung cancer (NSCLC) and EGFR mutation-positive tumors, but the economic impact of this practice is unclear.MethodsA decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The clinical data were primarily obtained from the results of a pivotal phase III trial that assessed gefitinib maintenance treatment in patients with advanced NSCLC. The cost data were derived from the perspective of the Chinese health care system. The primary outcome was the incremental cost-effectiveness ratio (ICER) at a willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China. Sensitivity analyses were used to explore the impact of uncertainty regarding the results. The impact of the gefitinib patient assistance program (GPAP) was evaluated.ResultsAfter EGFR genotyping, gefitinib maintenance treatment for advanced NSCLC with EGFR mutations increased the life expectancy by 0.74 years and 0.46 QALYs compared with routine follow-up at an additional cost of $26,149.90 USD ($7,178.20 with the GPAP). The ICER for gefitinib maintenance was $57,066.40 and $15,664.80 per QALY gained (at a 3% discount rate) without and with the GPAP, respectively. The utility of progression free survival, the hazard ratio of progression-free survival for gefitinib treatment and the cost of gefitinib per dose were the three factors that had the greatest influence on the results.ConclusionsThese results indicate that gene-guided maintenance therapy with gefitinib with the GPAP might be a cost-effective treatment option.

O2-025 - Efficacy and Safety of Bevacizumab in Combination with Carboplatin and Paclitaxel for Patients with Advanced EGFR Mutation-Positive Non-Small Cell Lung Cancer

ABSTRACT Background Efficacy of bevacizumab in combination with platinum-based chemotherapy for EGFR mutation-positive non-small-cell lung cancer (NSCLC) is less well known. The purpose of this study was to determine the efficacy and safety of bevacizumab with carboplatin plus paclitaxel for patients with advanced EGFR mutation-positive NSCLC. Methods We retrospectively reviewed 22 consecutive patients with advanced EGFR mutation-positive NSCLC treated with bevacizumab with carboplatin plus paclitaxel at our institution from April 2010 to September 2011. Carboplatin AUC 6 and paclitaxel 200 mg/m2 for up to six cycles plus bevacizumab 15 mg/kg were administered intravenously every 3–4 weeks until disease progression or development of intolerance. Results Profile of patients included: median age was 63 years (range 36–71); male/female = 7/15; PS 0/1 = 4/18; EGFR mutation type exon 19 deletion/L858R in exon 21 = 11/11 and all patients had stage IV adenocarcinoma. Thirteen patients had received no prior chemotherapy and nine patients had been treated with EGFR tyrosine kinase inhibitors (EGFR TKIs). A partial response was achieved in 8 of 22 patients, and the overall response rate was 36%. The median progression-free survival (PFS) in all patients was 8.9 months. The response rate of patients who had received prior EGFR TKIs was 44% (4 of 9), as opposed to 31% (4 of 13) among untreated patients (P = 0.66). Median PFS was 8.9 months in prior EGFR TKIs-treated patients, compared with 6.1 months in untreated patients (P = 0.66). The median overall survival has not been reached. The most common adverse events were grade 3/4 neutropenia (45%) and grade 1 bleeding events (50%). There were no severe pulmonary hemorrhage and treatment-related deaths. Conclusions In patients with advanced EGFR mutation-positive NSCLC, prior EGFR TKIs therapy status is not significantly associated with efficacy of bevacizumab with carboplatin plus paclitaxel.