<abstract xmlns="http://www.w3.org/1999/xhtml">

<sec id="j_raon-2017-0029_s_023">
<h3>Background</h3>
<p>When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment.</p>
</sec>
<sec id="j_raon-2017-0029_s_024">
<h3>Methods</h3>
<p>Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson’s correlation coefficient and the coefficient of determination, separately for first-line and second-line setting.</p>
</sec>
<sec id="j_raon-2017-0029_s_025">
<h3>Results</h3>
<p>The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with non-squamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months.</p>
</sec>
<sec id="j_raon-2017-0029_s_026">
<h3>Conclusions</h3>
<p>Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.</p>
</sec>
</abstract>

Background
When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment.


Methods
Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson’s correlation coefficient and the coefficient of determination, separately for first-line and second-line setting.


Results
The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with non-squamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR-mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months.


Conclusions
Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR-mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.

Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors

Radiology and Oncology

This work is licensed under the Creative Commons Attribution 4.0 International License.

Background
When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with...

Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors

Article Category: Review

Published Online: Jul 18, 2017

Page range: 241 - 251

Received: May 03, 2017

Accepted: Jun 09, 2017

DOI: https://doi.org/10.1515/raon-2017-0029

© 2017 Matjaz Zwitter, Antonio Rossi, Massimo Di Maio, Maja Pohar Perme, Gilberto Lopes

This work is licensed under the Creative Commons Attribution 4.0 International License.