Dataset Information

Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients.

ABSTRACT:

Purpose

Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment.

Patients and methods

We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed. Multi-state modeling (MSM) and a Cox PH regression model with propensity score weights adjusted for clinicopathological variables between: diagnosis and PD and PD to death.

Results

123 stage IIIA-IV patients were identified with 104 meeting RECIST-1.1-PD criteria. This RECIST-1.1-PD criteria subset included females (64.6%), Asians (39.4%), never/non-smokers (55.8%), and exon 19 deletion carriers (44.2%). Commonest treatment beyond initial-PD was continuing TKI alone (46/104), with another 21 patients continuing TKI plus additional systemic therapy. The median OS for patients who continued TKI treatment at initial-PD was 21.1 months versus 15.6 months for patients who discontinued TKI, p = 0.006. Via MSM analysis, continuing TKI at initial-PD followed by other systemic therapy was associated with an 83% reduced death risk, adjusted HR: 0.17 (95% CI: 0.07, 0.39). In the Cox PH model, ever-smokers with an exon 19 deletion had increased risk of death after PD (adjusted HR: 3.19, 95% CI: 1.54, 6.58), as did exon 21 mutation carriers, (adjusted HR: 2.10, 95% CI: 1.10, 4.00) and females (adjusted HR: 3.19, 95% CI: 1.54, 6.58).

Conclusion

Subsequent systemic therapy after continuing TKI at initial-PD reduced the risk of death. Additionally, our data suggest that positive smoking history increases death risk for some EGFR mutation types and females.

SUBMITTER: Tudor RA

PROVIDER: S-EPMC5544231 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients.

Tudor Roxana Alina RA D'Silva Adrijana A Tremblay Alain A MacEachern Paul P Morris Don D Brenner Darren D Kopciuk Karen K Bebb Dafydd Gwyn DG

PloS one 20170804 8

<h4>Purpose</h4>Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment.<h4>Patients and methods</h4>We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut+) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurre ...[more]

PMID: 28777825

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Project description:BACKGROUND:HER2 expression and amplification are observed in ~15% of tumour biopsies from patients with a sensitising EGFR mutation who develop EGFR TKI resistance. It is unknown whether HER2 targeting in this setting can result in tumour responses. METHODS:A single arm phase II study was performed to study the safety and efficacy of trastuzumab and paclitaxel treatment in patients with a sensitising EGFR mutation who show HER2 expression in a tumour biopsy (IHC???1) after progression on EGFR TKI treatment. Trastuzumab (first dose 4?mg/kg, thereafter 2?mg/kg) and paclitaxel (60?mg/m2) were dosed weekly until disease progression or unacceptable toxicity. The primary end-point was tumour response rate according to RECIST v1.1. RESULTS:Twenty-four patients were enrolled. Nine patients were exon 21 L858R positive and fifteen exon 19 del positive. Median HER2 IHC was 2+ (range 1-3). For 21 patients, gene copy number by in situ hybridisation could be calculated: 5 copies/nucleus (n?=?9), 5-10 copies (n?=?8), and >10 copies (n?=?4). An objective response was observed in 11/24 (46%) patients. Highest response rates were seen for patients with 3+ HER2 IHC (12 patients, ORR 67%) or HER2 copy number ?10 (4 patients, ORR 100%). Median tumour change in size was 42% decrease (range -100% to +53%). Median duration of response was 5.6 (95% confidence interval [CI], 3.8 to 7.3) months. Treatment toxicity was mild with four patients experiencing grade ?3 toxicity, including fatigue, neuropathy, neutropaenia, urinary tract infection, and pneumonitis. CONCLUSIONS:Trastuzumab-paclitaxel induces objective tumour responses in 46% of EGFR TKI pretreated patients with an activating EGFR mutation and HER2 expression. The treatment was well tolerated. The relation between response rate and HER2 expression level and copy number suggests effective HER2 targeting by trastuzumab, although the combination with paclitaxel does not allow to determine the relative contribution of the individual drugs in terms of treatment efficacy.

Dataset Information

Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients.

Purpose

Patients and methods

Results

Conclusion

Publications

Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients.

Similar Datasets

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