Efficacy of Pemetrexed as Second-Line Therapy in Advanced NSCLC after Either Treatment-Free Interval or Maintenance Therapy with Gemcitabine or Erlotinib in IFCT-GFPC 05-02 Phase III Study

Bylicki, Olivier; Ferlay, Céline; Chouaïd, C.; Lavolé, A.; Dubos, Catherine; Westeel, Virginie; Créquit, Jacky; Corre, R.; Vergnenègre, A.; Monnet, I.; Caer, H. Le; Fournel, P.; Vaylet, F.; Falchero, L.; Poudenx, M.; Linard, Pauline; Pérol, David; Zalcman, G.; Pérol, Maurice

doi:10.1097/jto.0b013e31828cb505

Cited by 10 publications

(4 citation statements)

References 33 publications

(35 reference statements)

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“…No significant difference in os was observed, but a trend toward improved survival was evident in both the erlotinib group (hr: 0.80; 95% ci: 0.61 to 1.05; p = 0.13) and the gemcitabine group (hr: 0.81; 95% ci: 0.61 to 1.07; p = 0.109) compared with the observation group. No outstanding adverse effects occurred in the erlotinib group 107 .…”

Section: Maintenancementioning

confidence: 99%

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Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

et al. 2015

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Section: Maintenancementioning

confidence: 99%

“…Bylicki et al 107 randomized patients to maintenance therapy with erlotinib, gemcitabine, or observation. In the observation group, patients received no treatment.…”

Section: Maintenancementioning

confidence: 99%

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

et al. 2015

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“…As the higher dose did not improve efficacy, 500 mg/m 2 remains the recommended dose of pemetrexed [Cullen et al 2008]. It has also been proven that second-line pemetrexed efficacy was not influenced by maintenance therapy with gemcitabine continuation or switch maintenance with erlotinib [Bylicki et al 2013]. Pemetrexed was also compared with gefitinib in an Asian population of EGFR wild-type nonsquamous NSCLC with a significant improvement in PFS for pemetrexed (4.8 versus 1.6 months, p < 0.001) [Zhou et al 2014].…”

Section: Pemetrexed Monotherapymentioning

confidence: 99%

Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

et al. 2016

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Non-small cell lung cancer (NSCLC) is still the leading cause of cancer-related death, and the treatment of advanced NSCLC relies on systemic treatments. During the last decade, pemetrexed, an antifolate agent, gradually became a key component of the treatment for patients with advanced nonsquamous NSCLC. It has indeed been shown to be efficient for first-line, maintenance and second- or third-line treatment in this subgroup of NSCLC. Moreover, it is usually well tolerated, with few grade 3 and 4 toxicities. Several studies have tried to identify predictive biomarkers of pemetrexed efficacy. Due to pemetrexed's mechanism of action, thymidilate synthase expression predictive value was investigated but could not be demonstrated. Currently, more than 400 trials of pemetrexed for the treatment of nonsquamous NSCLC are ongoing.

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“…Platinum-based chemotherapy is used as second-line therapy, whereas pemetrexed or docetaxel is used as third-line therapy in NSCLC patients in the event of disease progression after first-line EGFR-TKI therapy. They showed a median PFS of 6.4 months and a median overall survival of 19.2 months as salvage chemotherapies [6, 7]. Overcoming EGFR-TKI resistance is important for prolonging overall survival.…”

Section: Introductionmentioning

confidence: 99%

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

et al. 2019

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BackgroundProtein tyrosine kinase 2 (PTK2) expression has been reported in various types of human epithelial cancers including lung cancer; however, the role of PTK2 in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) has not been elucidated. We previously reported that pemetrexed-resistant NSCLC cell line PC-9/PEM also acquired EGFR-TKI resistance with constitutive Akt activation, but we could not find a therapeutic target.MethodsCell viability in EGFR-mutant NSCLC cell lines was measured by the WST-8 assay. Phosphorylation antibody array assay for receptor tyrosine kinases was performed in PC-9 and PC-9/PEM cell lines. We evaluated the efficacy of EGFR and PTK2 co-inhibition in EGFR-TKI-resistant NSCLC in vitro. Oral defactinib and osimertinib were administered in mice bearing subcutaneous xenografts to evaluate the efficacy of the treatment combination in vivo. Both the PTK2 phosphorylation and the treatment combination efficacy were evaluated in erlotinib-resistant EGFR-mutant NSCLC cell lines.ResultsPTK2 was hyperphosphorylated in PC-9/PEM. Defactinib (PTK2 inhibitor) and PD173074 (FGFR inhibitor) inhibited PTK2 phosphorylation. Combination of PTK2 inhibitor and EGFR-TKI inhibited Akt and induced apoptosis in PC-9/PEM. The combination treatment showed improved in vivo therapeutic efficacy compared to the single-agent treatments. Furthermore, erlotinib-resistant NSCLC cell lines showed PTK2 hyperphosphorylation. PTK2 inhibition in the PTK2 hyperphosphorylated erlotinib-resistant cell lines also recovered EGFR-TKI sensitivity.ConclusionPTK2 hyperphosphorylation occurs in various EGFR-TKI-resistant NSCLCs. Combination of PTK2 inhibitor and EGFR-TKI (defactinib and osimertinib) recovered EGFR-TKI sensitivity in the EGFR-TKI-resistant NSCLC. Our study result suggests that this combination therapy may be a viable option to overcome EGFR-TKI resistance in NSCLC.

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Efficacy of Pemetrexed as Second-Line Therapy in Advanced NSCLC after Either Treatment-Free Interval or Maintenance Therapy with Gemcitabine or Erlotinib in IFCT-GFPC 05-02 Phase III Study

Abstract: Maintenance therapy with gemcitabine continuation or erlotinib does not seem to impair efficacy of second-line pemetrexed comparatively to administration after a treatment-free interval.

Cited by 10 publications

References 33 publications

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

Use of the Epidermal Growth Factor Receptor Inhibitors Gefitinib, Erlotinib, Afatinib, Dacomitinib, and Icotinib in the Treatment of Non-Small-Cell Lung Cancer: A Systematic Review

Pemetrexed for advanced stage nonsquamous non-small cell lung cancer: latest evidence about its extended use and outcomes

Protein tyrosine kinase 2: a novel therapeutic target to overcome acquired EGFR-TKI resistance in non-small cell lung cancer

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