Dataset Information

Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study.

ABSTRACT:

Background

Clinical guidelines advise osimertinib as preferred first line treatment for advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with deletions in exon 19 (del19) or exon 21 L858R mutation. However, for first-line osimertinib the real world overall survival (OS) in mutation subgroups remains unknown. Therefore, the aim of this study was to evaluate the real-world OS of those patients treated with different generations of EGFR-tyrosine kinase inhibitors (TKI), and to identify predictors of survival.

Methods

Using real-world data from the Netherlands Cancer Registry (NCR) we assessed patients diagnosed with stage IV NSCLC with del19 or L858R mutation between January 1, 2015, and December 31, 2020, primarily treated with then regularly available TKIs (including osimertinib).

Findings

Between January 1, 2015, and December 31, 2020, 57,592 patients were included in the NCR. Within this cohort we identified 1109 patients, 654 (59%) with del19 and 455 (41%) with L858R mutations, respectively; 230 (21%) patients were diagnosed with baseline brain metastases (BM). Patients were treated with gefitinib (19%, 213/1109), erlotinib (42%, 470/1109), afatinib (15%, 161/1109) or osimertinib (24%, 265/1109). Median OS was superior for del19 versus L858R (28.4 months (95% CI 25.6-30.6) versus 17.7 months (95% CI 16.1-19.5), p < 0.001. In multivariable analysis, no difference in survival was observed between various TKIs in both groups. Only in the subgroup of patients with del19 and baseline BM, a benefit was observed for treatment with osimertinib.

Interpretation

In this nationwide real-world cohort, survival of Dutch patients with advanced NSCLC and an EGFR del19 mutation was superior versus those harboring an L858R mutation. Osimertinib performed only better as first-line treatment in patients with del19 and BM.

Funding

None.

SUBMITTER: Gijtenbeek RGP

PROVIDER: S-EPMC9932646 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

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Publications

Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study.

Gijtenbeek Rolof G P RGP Damhuis Ronald A M RAM van der Wekken Anthonie J AJ Hendriks Lizza E L LEL Groen Harry J M HJM van Geffen Wouter H WH

The Lancet regional health. Europe 20230206

<h4>Background</h4>Clinical guidelines advise osimertinib as preferred first line treatment for advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with deletions in exon 19 (del19) or exon 21 L858R mutation. However, for first-line osimertinib the real world overall survival (OS) in mutation subgroups remains unknown. Therefore, the aim of this study was to evaluate the real-world OS of those patients treated with different generations of EGFR-tyrosine ki ...[more]

PMID: 36817181

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Project description:BackgroundThis study aimed to investigate the efficacy of immunotherapy, as monotherapy or in combination, comparing to chemotherapy with or without anti-angiogenesis for advanced non-small cell lung cancer (NSCLC) patients progressing to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).MethodsWe retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who received immune checkpoint inhibitors (ICI) and/or chemotherapy after EGFR-TKIs failure at Shanghai Chest Hospital between Aug 2016 and Oct 2022. According to the subsequent immunotherapy regimen, the patients were assigned to ICI monotherapy (IM), IO plus anti-angiogenesis (IA), ICI plus chemotherapy (IC), ICI plus chemotherapy plus anti-angiogenesis (ICA). Eligible patients undergoing standard chemotherapy were assigned to chemotherapy plus anti-angiogenesis (CA) and chemotherapy alone (CM). Efficacy was evaluated according to the RECIST 1.1version, and calculated the objective response rate (ORR) and disease control rate (DCR). Survival curves were plotted using the Kaplan-Meier method, and the median progression-free survival (PFS) was calculated. Differences among survival curves of the six groups were assessed using the log-rank test.ResultsA total of 237 advanced NSCLC patients with EGFR mutations were included in this study. Of the 160 patients who received immunotherapy, 57 received ICI monotherapy, 27 received ICI plus anti-angiogenesis therapy, 43 received ICI plus chemotherapy, and 33 received ICI plus anti-angiogenesis plus chemotherapy. 77 patients received standard chemotherapy, of which 30 received chemotherapy plus anti-angiogenesis and 47 received chemotherapy alone. Patients in ICA group showed significant longer PFS than IM (7.2 vs 1.9 months, P=0.011), IA (7.2 vs 4.8 months, P=0.009) and CM group (7.2 vs 4.4 months, P=0.005). There was no significant difference in PFS between the ICA and IC (7.2 vs 5.6 months, P=0.104) or CA (7.2 vs 6.7 months, P=0.959) group. Meanwhile, the ICA group showed the highest ORR and DCR (36.4% and 90.9%) compared to the other five groups. The IC group had a higher ORR than the IA and CA group (32.6% vs 7.4% vs 10.0%, respectively), but the DCR was comparable (79.1% vs 74.1% vs 76.7%, respectively). The ORR of the CM group was 6.4% and the DCR was 66.0%. IM group showed the lowest ORR and DCR (1.8% and 36.8%). Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 9 (27.3%) patients in the ICA group, 6 (20.0%) in the CA group, 7 (14.9%) in the CM group, 5 (11.6%) in the IC group, 5 (8.8%) in the IM group, and 2 (7.4%) in the IA group.ConclusionNSCLC patients with positive EGFR mutations after EGFR-TKIs failure received subsequent immunotherapy plus anti-angiogenesis and chemotherapy are likely to have more benefits in ORR, DCR and mPFS.

Project description:ImportanceMetformin hydrochloride is emerging as a repurposed anticancer drug. Preclinical and retrospective studies have shown that it improves outcomes across a wide variety of neoplasms, including lung cancer. Particularly, evidence is accumulating regarding the synergistic association between metformin and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs).ObjectiveTo assess the progression-free survival (PFS) in patients with advanced lung adenocarcinoma who received treatment with EGFR-TKIs plus metformin compared with those who received EGFR-TKIs alone.Design, setting, and participantsOpen-label, randomized, phase 2 trial conducted at the Instituto Nacional de Cancerología (INCan), Mexico City, Mexico. Eligible patients were 18 years or older, had histologically confirmed stage IIIB-IV lung adenocarcinoma with an activating EGFR mutation.InterventionsPatients were randomly allocated to receive EGFR-TKIs (erlotinib hydrochloride, afatinib dimaleate, or gefitinib at standard dosage) plus metformin hydrochloride (500 mg twice a day) or EGFR-TKIs alone. Treatment was continued until occurrence of intolerable toxic effects or withdrawal of consent.Main outcomes and measuresThe primary outcome was PFS in the intent-to-treat population. Secondary outcomes included objective response rate, disease control rate, overall survival (OS), and safety.ResultsBetween March 31, 2016, and December 31, 2017, a total of 139 patients (mean [SD] age, 59.4 [12.0] years; 65.5% female) were randomly assigned to receive EGFR-TKIs (n = 70) or EGFR-TKIs plus metformin (n = 69). The median PFS was significantly longer in the EGFR-TKIs plus metformin group (13.1; 95% CI, 9.8-16.3 months) compared with the EGFR-TKIs group (9.9; 95% CI, 7.5-12.2 months) (hazard ratio, 0.60; 95% CI, 0.40-0.94; P = .03). The median OS was also significantly longer for patients receiving the combination therapy (31.7; 95% CI, 20.5-42.8 vs 17.5; 95% CI, 11.4-23.7 months; P = .02).Conclusions and relevanceTo our knowledge, this is the first study to prospectively show that the addition of metformin to standard EGFR-TKIs therapy in patients with advanced lung adenocarcinoma significantly improves PFS. These results justify the design of a phase 3, placebo-controlled study.Trial registrationClinicalTrials.gov identifier: NCT03071705.

Project description:Additional variables for a nationwide hip fracture registry must be carefully chosen to prevent unnecessary registry load. A registry pilot in seven hospitals resulted in recommending polypharmacy, serum hemoglobin at admittance, and questions screening for risk of delirium to be used in case-mix correction and for development of quality indicators.PurposeClinical registries help improve the quality of care but come at the cost of registration load. Datasets should therefore be as compact as possible; however, variables are usually chosen empirically. This study aims to evaluate potential variables with additional value to improve the nationwide Dutch Hip Fracture Audit (DHFA).MethodsAn expert panel selected eleven new variables for the DHFA, which were tested in a prospective cohort of all hip fracture patients treated in 2018 and 2019 in seven pilot hospitals participating in the DHFA. The association of these eleven variables with complications, mortality, and functional outcomes at 3 months was analyzed using multivariable logistic regression analysis. Based on the results, a proposal for variables to add to the dataset of the DHFA was made.ResultsIn 4.904 analyzed patients, three tested variables had significant associations (p < 0.01) with outcomes: polypharmacy with complications (aOR 1.34), serum hemoglobin at admittance with complications (aOR 0.63) and mortality (aOR for 30-day mortality 0.78), and a set of questions screening for risk of delirium with complications in general (aOR 1.55), e.g., delirium (aOR 2.98), and decreased functional scores at three months (aOR 1.98).ConclusionThis study assesses potential new variables for a hip fracture registry. Based on the results of this study, we recommend polypharmacy, serum hemoglobin at admittance, and questions screening for risk of delirium to be used in case-mix correction and for the development of quality indicators. Incorporating these variables in the DHFA dataset may contribute to better and clinically relevant quality indicators.

Project description:ObjectivesTyrosine kinase inhibitors (TKIs) are the primary therapeutic option for patients with advanced-stage epidermal growth factor receptor-mutant (EGFR-m) lung adenocarcinoma. However, the role of EGFR-TKIs in advanced-stage lung cancer is uncertain regardless of therapeutic methods. This study investigated the outcome of the impact of epidermal growth factor receptor (EGFR)-TKI in patients with advanced lung adenocarcinoma treated with various therapeutic strategies.MethodsThis retrospective analysis used cancer registry data from 1159 patients with lung cancer treated between January 2015 and December 2017 at Tri-Service General Hospital. Only patients with lung adenocarcinoma stages 3B and four were selected for the study. All lung adenocarcinoma patients with ever TKI treatment had an EGFR mutation.ResultsThree-hundred sixty-two patients with advanced lung adenocarcinoma with complete medical records were enrolled. According to personalized therapeutic processes, they were divided into nine groups: only TKI treatment, only chemotherapy (CT), TKI with lung cancer salvage surgery, TKI with CT, TKI with radiotherapy (RT), CT with lung cancer salvage surgery, CT with RT, TKI with CT, and lung cancer salvage surgery. A multivariate Cox regression analysis showed TKI with lung cancer salvage surgery (HR: 4.675, p = 0.005) is the only good prognostic treatment. The poor predictors for overall survival were only CT (HR: 0.336, p = 0.048) and TKI with CT (HR: 0.359, p = 0.023). Kaplan-Meier survival analysis showed a statistical significance in an average overall survival (OS) of ever TKI treatment and never TKI treatment (33.24 vs. 17.64 months, p < 0.001). Furthermore, TKI usage duration was statistically increased in TKI with lung cancer salvage surgery (40.4 ± 20.7 vs 14.96 ± 13.13 months, p < 0.001). The survival rate (p = 0.033) and OS (p < 0.001) in lung cancer salvage surgery were statistically better than the group of TKI without surgery.ConclusionThe best therapeutic strategy for advanced lung adenocarcinoma is TKI with lung cancer salvage surgery, according to significantly longer OS and better survival. It also prolonged TKI usage. Mutated EGFR lung adenocarcinoma patients with ever TKI treatment had significantly better survival than with other treatments. Regardless of the combination of other treatments, EGFR mutation with TKI therapy is recommended as a positive prognostic factor for patients with lung adenocarcinoma.

Dataset Information

Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study.

Background

Methods

Findings

Interpretation

Funding

Publications

Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study.

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