Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7)

Paz‐Ares, Luis; Tan, Eng Huat; Zhang, L.; Hirsh, Vera; O’Byrne, Kenneth J.; Boyer, Michael; Yang, Jin-Ji; Mok, Tony; Lee, K.H.; Lü, Shun; Shi, Yuankai; Sw, Kim; Laskin, Janessa; Dw, Kim; Laurie, Scott A.; Kölbeck, Karl‐Gustav; Fan, Jean; Dodd, Nigel; Märten, Angela; Park, K.

doi:10.1093/annonc/mdw435.42

Cited by 13 publications

(10 citation statements)

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“…However, in subgroup analysis, patients with BM showed no significant difference in PFS between gefitinib and afatinib treatment groups. Furthermore, regarding OS, there was no statistical significance between these two groups . In the CTONG 0901 study, erlotinib was not superior to gefitinib in PFS or OS.…”

Section: Discussionmentioning

confidence: 92%

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib

Yao

Liao

et al. 2017

The Oncologist

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Background. This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. Materials and Methods. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. Results. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] 2), smoking index (20 pack-years), liver

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Section: Discussionmentioning

confidence: 92%

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib

Yao

Liao

et al. 2017

The Oncologist

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“…However, an unplanned pooled OS analysis of patients included in the LUX-Lung 3 or LUX-Lung 6 phase III trials demonstrated an OS benefit for afatinib compared to platinum-based chemotherapy in patients whose tumors harbor EGFR Del19 mutations vs. EGFR L858R mutations: 27.3 vs. 24.3 months, respectively [hazard ratio (HR) 0.81; 95% confidence interval (CI), 0.66–0.99; p = 0.037] (14). However, this benefit was not confirmed in the phase IIb LUX-Lung 7 designed to compare head-to-head afatinib with gefitinib in the first-line treatment of patients with EGFR -mutant NSCLC (15). Unfortunately, the majority of patients progress after a median of 12 months treatment with first-line TKIs, and multiple mechanisms of acquired resistance have been identified.…”

Section: Introductionmentioning

confidence: 99%

Next-Generation EGFR Tyrosine Kinase Inhibitors for Treating EGFR-Mutant Lung Cancer beyond First Line

Sullivan

Planchard

2017

Front. Med.

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Tyrosine kinase inhibitors (TKIs) against the human epidermal growth factor receptor (EGFR) are now standard treatment in the clinic for patients with advanced EGFR mutant non-small-cell lung cancer (NSCLC). First-generation EGFR TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR tyrosine kinase domain, have resulted in a significant improvement in outcome for NSCLC patients with activating EGFR mutations (L858R and Del19). However, after a median duration of response of ~12 months, all patients develop tumor resistance, and in over half of these patients this is due to the emergence of the EGFR T790M resistance mutation. The second-generation EGFR/HER TKIs were developed to treat resistant disease, targeting not only T790M but EGFR-activating mutations and wild-type EGFR. Although they exhibited promising anti-T790M activity in the laboratory, their clinical activity among T790M+ NSCLC was poor mainly because of dose-limiting toxicity due to simultaneous inhibition of wild-type EGFR. The third-generation EGFR TKIs selectively and irreversibly target EGFR T790M and activating EGFR mutations, showing promising efficacy in NSCLC resistant to the first- and second-generation EGFR TKIs. They also appear to have lower incidences of toxicity due to the limited inhibitory effect on wild-type EGFR. Currently, the first-generation gefitinib and erlotinib and second-generation afatinib have been approved for first-line treatment of metastatic NSCLC with activating EGFR mutations. Among the third-generation EGFR TKIs, osimertinib is today the only drug approved by the Food and Drug Administration and the European Medicines Agency to treat metastatic EGFR T790M NSCLC patients who have progressed on or after EGFR TKI therapy. In this review, we summarize the available post-progression therapies including third-generation EGFR inhibitors and combination treatment strategies for treating patients with NSCLC harboring EGFR mutations and address the known mechanisms of resistance.

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“…A randomized phase II trial comparing a first-versus a second-generation EGFR TKI (gefitinib and afatinib, respectively) in this setting failed to demonstrate any difference in OS between the two drugs, even though afatinib treatment increased both progression-free survival (PFS) and time to treatment failure (TTF) 34,35 . As of today, the agent of choice for first-line treatment in EGFR mutated patients is mainly based on the physician's expertise with different molecules and their different toxicity profiles.…”

Section: Oncogene-driven Nsclc Egfr Mutated Nsclcmentioning

confidence: 99%

Lung Cancer Management: where are we in 2017?

Scagliotti¹,

Bironzo²,

Rosell³

2017

BRN

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Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC): overall survival (OS) data from the phase IIb trial LUX-Lung 7 (LL7)

Cited by 13 publications

References 0 publications

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib

Next-Generation EGFR Tyrosine Kinase Inhibitors for Treating EGFR-Mutant Lung Cancer beyond First Line

Lung Cancer Management: where are we in 2017?

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