Chemotherapy for patients with EGFR-mutated NSCLC after progression on EGFR-TKI’s: Exploration of efficacy of unselected treatment in a multicenter cohort study

Steendam, Christi M.J.; Ernst, Sophie M.; Badrising, Sushil K.; Paats, Marthe S.; Aerts, Joachim; Langen, Adrianus J de; Dingemans, Anne‐Marie C.

doi:10.1016/j.lungcan.2023.107248

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…Real-world outcomes were also examined in a small retrospective study of 135 patients with EGFR -mutated advanced NSCLC who received subsequent therapy in 2015 to 2021 after EGFR TKIs. Treated at two tertiary cancer centers in the Netherlands, these patients received a variety of chemotherapy regimens; and median OS was 15.3 months (95% CI, 11.6–18.9), slightly longer than in the present study, with no significant difference detected among regimens, the most common of which was pemetrexed-platinum ( 36 ).…”

Section: Discussioncontrasting

confidence: 64%

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors

Halmos,

Rai,

Min

et al. 2024

Front. Oncol.

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BackgroundFront-line therapy with an EGFR tyrosine kinase inhibitor (TKI) is the standard of care for treating patients with advanced nonsquamous NSCLC with the common sensitizing EGFR exon 19 deletion and exon 21 L858R point mutations. However, EGFR TKI resistance inevitably develops. The optimal subsequent therapy remains to be identified, although platinum-containing chemotherapy regimens are often administered. Our objectives were to describe baseline characteristics, survival, and subsequent treatment patterns for patients with advanced nonsquamous NSCLC with EGFR exon 19 deletion or L858R mutation who received a platinum-based combination regimen after front-line EGFR TKI therapy.MethodsThis retrospective study used a nationwide electronic health record-derived deidentified database to select adult patients with advanced nonsquamous NSCLC, evidence of EGFR exon 19 deletion or L858R mutation, and ECOG performance status of 0-2 who initiated platinum-containing chemotherapy, with or without concomitant immunotherapy, from 1-January-2011 to 30-June-2020 following receipt of any EGFR TKI as first-line therapy or, alternatively, a first- or second-generation EGFR TKI (erlotinib, afatinib, gefitinib, dacomitinib) as first-line therapy followed by the third-generation EGFR TKI osimertinib as second-line therapy. Data cut-off was 30-June-2022. The Kaplan-Meier method was used to estimate overall survival (OS) after initiation of pemetrexed-platinum (n=119) or any platinum-based combination regimen (platinum cohort; n=311).ResultsThe two cohorts included two-thirds women (65%-66%) and 57%-58% nonsmokers; median ages were 66 and 65 years in pemetrexed-platinum and platinum cohorts, respectively. Median OS was 10.3 months (95% CI, 8.1-13.9) from pemetrexed-platinum initiation and 12.4 months (95% CI, 10.2-15.2) from platinum initiation; 12-month survival rates were 48% and 51%, respectively; 260 patients (84%) had died by the end of the study.ConclusionThe suboptimal survival outcomes recorded in this study demonstrate the unmet need to identify more effective subsequent treatment regimens for patients with EGFR-mutated advanced nonsquamous NSCLC after EGFR TKI resistance develops.

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Section: Discussioncontrasting

confidence: 64%

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors

Halmos,

Rai,

Min

et al. 2024

Front. Oncol.

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“…The corresponding efficacy parameters noted in the patients who received chemotherapy in the AURA3 trial were an ORR of 31%, median PFS of 4.4 months (95% CI, 4.2–5.6) and median OS of 22.5 months (95% CI, 20.2, 28.8). A recent retrospective European study in 135 patients reported that chemotherapy after progression on first-line TKI resulted in a median PFS of 5.4 months (95% CI, 4.7–6.1), and median OS of 15.3 months (95% CI, 116–18.9) [ 26 ]. In an earlier real world study report, we found that osimertinib at 80 mg a day in the second line and beyond setting for 17 patients with EGFR T790M mutation led to an ORR of 55% and DCR of 90.9%; survival data were immature at the time of this report [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced frequency dosing of osimertinib in EGFR-mutant non-small cell lung carcinoma: real world data

Noronha,

Sahu,

Kapoor

et al. 2024

ecancer Journal

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Introduction Osimertinib is more efficacious and as safe as first-generation epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors. However, osimertinib is not affordable for most patients in developing nations. Moreover, the minimum biologically effective dose of osimertinib may be less than the approved dose. Materials and methods This was a retrospective observational multicentric study aimed to describe the efficacy (objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS)) and toxicity of osimertinib 80 mg orally administered less frequently than daily (ranging from every other day to once-a-week) in patients with EGFR-mutated non-small cell lung cancer. Results Between January 2021 and August 2023, we enrolled 22 patients. Six received osimertinib 80 mg once-a-week, nine received 80 mg once-in-3-days and seven received 80 mg on alternate days. Responses included 0 complete responses, 7 (31.8%) partial responses, 9 (40.9%) stable disease and 5 (22.7%) progressive disease. ORR was 31.8%, and DCR was 72.7%. Median PFS was 9.2 months (95% confidence interval (CI) 2.9–15.7), and median OS was 17.8 months (95% CI, 3.2–32.6). In patients who received reduced frequency osimertinib in the second line and beyond, the ORR was 29.4%, DCR was 70.5%, median PFS was 5.9 months (95% CI, 1.1–10.6) and median OS was 17.6 months (95% CI, 2.9–32.2). Grade 3 and higher toxicities were noted in 8 (36.3%) patients. Conclusion Less frequent dosing of osimertinib may be a valid treatment option, especially in the second line and beyond setting in patients who cannot afford full dose daily osimertinib. This may provide an additional treatment option with a similar toxicity profile as that of standard dose osimertinib.

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“…Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have become common first-line treatments for NSCLC patients who harbor an EGFR mutation. 84 EGFR inhibitors are a group of monoclonal antibodies given to patients who have an EGFR mutation in their cancer, which can be as common as 90% of patients. 85 However, within 50% of these cases, an additional EGRF mutation occurs that leads to the enhancement of kinase activity increases the affinity of ATP to EGFR, outcompetes TKI binding, and ultimately limits the effectiveness of these drugs.…”

Section: Chemotherapymentioning

confidence: 99%

Metabolomics at the tumor microenvironment interface: Decoding cellular conversations

Berrell,

Sadeghirad,

Blick

et al. 2023

Medicinal Research Reviews

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Cancer heterogeneity remains a significant challenge for effective cancer treatments. Altered energetics is one of the hallmarks of cancer and influences tumor growth and drug resistance. Studies have shown that heterogeneity exists within the metabolic profile of tumors, and personalized‐combination therapy with relevant metabolic interventions could improve patient response. Metabolomic studies are identifying novel biomarkers and therapeutic targets that have improved treatment response. The spatial location of elements in the tumor microenvironment are becoming increasingly important for understanding disease progression. The evolution of spatial metabolomics analysis now allows scientists to deeply understand how metabolite distribution contributes to cancer biology. Recently, these techniques have spatially resolved metabolite distribution to a subcellular level. It has been proposed that metabolite mapping could improve patient outcomes by improving precision medicine, enabling earlier diagnosis and intraoperatively identifying tumor margins. This review will discuss how altered metabolic pathways contribute to cancer progression and drug resistance and will explore the current capabilities of spatial metabolomics technologies and how these could be integrated into clinical practice to improve patient outcomes.

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Chemotherapy for patients with EGFR-mutated NSCLC after progression on EGFR-TKI’s: Exploration of efficacy of unselected treatment in a multicenter cohort study

Cited by 7 publications

References 26 publications

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors

Real-world outcomes on platinum-containing chemotherapy for EGFR-mutated advanced nonsquamous NSCLC with prior exposure to EGFR tyrosine kinase inhibitors

Reduced frequency dosing of osimertinib in EGFR-mutant non-small cell lung carcinoma: real world data

Metabolomics at the tumor microenvironment interface: Decoding cellular conversations

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