Dataset Information

Real-world outcomes of first- and second-generation tyrosine kinase inhibitors first-line in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer: A retrospective observational cohort study.

ABSTRACT: The sequencing of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC) remains a matter of controversy. This cohort study analyzed the overall survival (OS) and progression-free survival (PFS) of afatinib compared with erlotinib and gefitinib first-line. EGFRm+, advanced NSCLC patients treated with either afatinib, erlotinib or gefitinib were retrospectively analyzed. A total of 107 patients were included. There was no statistically significant difference in PFS among the 3 groups. In the ≥ 60 years age group, the afatinib group had longer survival compared to the gefitinib group (p = 0.01). Median OS were 19.1, 22.9, and 35.6 months for gefitinib, erlotinib, and afatinib groups, respectively, with statistical significance between the gefitinib and afatinib groups (p = 0.009). Patients on afatinib also had longer median OS than erlotinib and gefitinib pooled together (35.5 versus 21.4 months; hazard ratio = 0.54, p = 0.016), despite similar median PFS. In conclusion, afatinib is a better choice compared to gefitinib or erlotinib for EGFRm+ patients. The OS obtained with afatinib is just 3 months shorter than osimertinib in the FLAURA trial. Direct comparison studies with osimertinib are still needed to determine optimal sequencing.

SUBMITTER: Ng WW

PROVIDER: S-EPMC8224855 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThere are limited comparisons of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in large, real-world cohorts of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations.MethodsPatients with advanced NSCLC (N = 612) with common EGFR mutations receiving first-line gefitinib/erlotinib and afatinib were grouped and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutations were analyzed.ResultsThe gefitinib/erlotinib and afatinib groups each contained 206 patients after matching. Compared with gefitinib/erlotinib, patients receiving afatinib achieved longer median PFS (16.3 versus 14.2 months; log-rank test p = 0.020) and had a lower risk of progression [hazard ratio (HR) 0.73 (95% confidence interval (CI), 0.57-0.94); p = 0.017]. Median OS (37.3 versus 34.2 months; log-rank test p = 0.500) and reduction in risk of death [HR 0.89 (95% CI, 0.65-1.23); p = 0.476] did not differ significantly between groups. T790M positivity was significantly higher in the gefitinib/erlotinib than afatinib group (70.9% versus 44.6%, p < 0.001). Multivariate analysis demonstrated that afatinib was independently associated with lower T790M positivity [odds ratio (OR) 0.27 (95% CI, 0.14-0.53); p < 0.001], whereas ⩾12 months PFS after EGFR-TKI treatment [OR 3.00 (95% CI, 1.56-5.98); p = 0.001] and brain metastasis [OR 2.12 (95% CI, 1.08-4.26); p = 0.030] were associated with higher T790M positivity. Sequential third-generation EGFR-TKI treatment was administered to 63 patients, in whom median OS after the second-third-generation and first-third-generation EGFR-TKI sequences were 38.8 and 29.1 months, respectively.ConclusionCompared with gefitinib/erlotinib, afatinib had a higher treatment efficacy and a lower secondary T790M positivity in a large, real-world cohort of Asian patients with EGFR-mutated NSCLC.

Project description:IntroductionEvidence is lacking on second-line and later treatments for patients with RAS wild-type colorectal cancer (CRC) who receive first-line anti-epidermal growth factor receptor (EGFR) antibody therapy. In this study, we explored the real-world treatment sequences, treatment duration, and factors associated with treatment sequences and durations in Japanese patients with CRC.MethodsThis retrospective observational cohort study used a Japanese administrative claims database (April 2008 to July 2021). Patients with confirmed CRC (presumed RAS wild-type) who received first-line FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) plus anti-EGFR therapy in or after May 2016, followed by second-line irinotecan-based chemotherapy plus an antiangiogenic drug, were included. Treatment durations were estimated by the Kaplan-Meier method. Cox regression analysis was used to identify factors associated with treatment duration.ResultsAnalysis populations consisted of 1163 (first-line and second-line) and 645 (third-line) patients. At the start of first-line therapy, 67.8% of patients were male, the mean age was 64 years, 83.4% had left-sided CRC, and 84.3% were prescribed FOLFOX plus panitumumab. For second-line therapy, patients were prescribed bevacizumab (63%), ramucirumab (27%), or aflibercept beta (10%). Median (95% CI) treatment durations from the start of second-line therapy to the end of antitumor drug therapies were similar for bevacizumab (12.5 months [11.2, 14.0]), ramucirumab (12.5 months [11.2, 14.8]), and aflibercept beta (14.0 months [10.4, 17.0]). Treatment duration from second-line was positively associated with first-line treatment duration of 6 months or more, CRC surgery before starting first-line therapy, and liver surgery during first-line therapy, and was negatively associated with use of nonsteroidal anti-inflammatory drugs before second-line therapy.ConclusionReal-world data revealed that all three antiangiogenic drugs were used as second-line therapy after first-line anti-EGFR antibodies and showed similar treatment durations.

Project description:BackgroundIn the phase 3 FLAURA trial, osimertinib was compared with first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as a first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib showed longer progression-free survival (PFS), overall survival (OS), and a similar safety profile. However, more studies demonstrating the effectiveness and safety of osimertinib as a first-line strategy are needed in real-world populations.MethodsWe enrolled 1,556 patients with EGFR-mutated stage IIIc-IV NSCLC from the CAPTRA-Lung database. All patients received either osimertinib (n=202) or a first-generation EGFR-TKI (n=1,354) as their initial treatment. To adjust for differences in baseline characteristics between two groups, 1:2 propensity score matching (PSM) was performed. Propensity scores included gender, age, Eastern Cooperative Oncology Group performance status score, smoking history, family history of tumor, pathology, EGFR mutations, and central nervous system (CNS) metastases. The standardized mean differences (SMD) before and after PSM were calculated to examine the balance of covariate distributions between two groups.ResultsAfter PSM, 202 patients receiving osimertinib and 404 patients receiving first-generation EGFR-TKIs were finally identified. SMD of each matched variable is less than 0.10. The median PFS was 19.4 months [95% confidence interval (CI): 14.3-24.4] in the osimertinib arm and 10.9 months (95% CI: 9.3-12.5) in the comparator arm [hazard ratio (HR) for progression, 0.47; 95% CI: 0.38-0.59; P<0.001). The median OS was 40.5 months (95% CI: 27.1-54.0) vs. 34.3 months (95% CI: 30.6-38.0) in two groups, respectively (HR for death, 0.76; 95% CI: 0.58-1.00; P=0.045). The incidence of grade 3 adverse events (AEs) between the two groups was 1% and 4.2%, respectively. No grade 4 AEs and treatment-related deaths were reported in both groups.ConclusionsIn real-world settings, osimertinib demonstrates longer PFS and OS, with a similar safety profile to that of comparator EGFR-TKIs when used as a first-line strategy in NSCLC patients.

Project description:IntroductionMetastatic pancreatic ductal adenocarcinoma (mPDAC) is a common cancer with poor survival outcomes. Although treatment options are limited, real-world treatment patterns and outcomes are not well understood, particularly beyond first-line treatment. This study described real-world treatment patterns and outcomes for mPDAC in the USA.MethodsThis retrospective analysis used electronic health record-derived de-identified data of patients with mPDAC diagnosed between January 1, 2014 and June 30, 2021. Treatments were classified into six groups: (1) standard combination chemotherapy; (2) nonstandard combination chemotherapy; (3) single-agent chemotherapy; (4) targeted therapy; (5) clinical study drugs; and (6) off-label therapies. Analyses were descriptive in nature. Treatment utilization and switching, and time on treatment and time to discontinuation, were described by first-line (1LOT) and second-line (2LOT) treatment groups. Median overall survival (mOS) from 1LOT and 2LOT was stratified by treatment group, and for 1LOT on the basis of whether patients received further treatment.Results1LOT included 6979 patients, 3241 (46%) of whom received further 2LOT. Standard combination chemotherapy was the most common 1LOT (70%) and 2LOT (46%). Nonstandard combination chemotherapy was used more as 2LOT (35%) than 1LOT (11%). First-line time on treatment was generally higher than second-line time on treatment, and time to discontinuation was lower than time on treatment. mOS in days (months) from 1LOT was 271 (8.9), 252 (8.3), 219 (7.2), 170 (5.6), 280 (9.2), and 182 (6.0), and mOS from 2LOT was 202 (6.6), 193 (6.3), 186 (6.1), 193 (6.3), 179 (5.9), and 97 (3.2), for groups 1-6, respectively. Within group 1, mOS from 1LOT was 318 days (10.4 months) for FOLFIRINOX and 241 days (7.9 months) for gemcitabine and nab-paclitaxel.ConclusionMost patients with mPDAC received 1LOT in line with clinical practice guidelines, yet mOS remains poor. This study highlights the need for novel therapies to demonstrate improved patient survival compared with therapies in current clinical practice guidelines.

Dataset Information

Real-world outcomes of first- and second-generation tyrosine kinase inhibitors first-line in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer: A retrospective observational cohort study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets