Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

Yang, James Chih‐Hsin; Wu, Yi Long; Schüler, Martin; Sebastian, Martin; Popat, Sanjay; Yamamoto, Nobuyuki; Zhou, Caicun; Hu, Chong; O’Byrne, Kenneth J.; Feng, Jifeng; Lü, Shun; Huang, Yunchao; Geater, Sarayut Lucien; Lee, Kye Young; Tsai, Chun Ming; Gorbunova, Vera; Hirsh, Vera; Bennouna, Jaafar; Орлов, С. В.; Mok, Tony; Boyer, Michael; Su, Wu Chou; Lee, Ki Hyeong; Kato, Terufumi; Massey, Dan; Shahidi, Mehdi; Zazulina, Victoria; Sequist, Lecia V.

doi:10.1016/s1470-2045(14)71173-8

Cited by 1,429 publications

(1,181 citation statements)

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“…15,16). Although afatinib showed clinical efficacy as single agent in the TKIs-na€ ve setting (17), the response rates in acquired resistance setting were below 10% (18). In xenograft models of TKI-resistant tumors harboring T790M mutation, dual inhibition of EGFR with afatinib plus cetuximab induced encouraging tumor shrinkage (19).…”

Section: Introductionmentioning

confidence: 99%

A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non–Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib

Lee

Sun

Lim

et al. 2016

Clinical Cancer Research

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Purpose: In this phase Ib/II study, we aimed to assess the safety and efficacy of afatinib plus nimotuzumab (N) in advanced nonsmall cell lung cancer (NSCLC) patients with acquired resistance to gefitinib or erlotinib.Experimental Design: In phase Ib stage, patients received afatinib (40 mg or 30 mg once daily) plus nimotuzumab (100 mg or 200 mg once weekly) for 28-day cycles to determine the recommended phase II dose (RPIID). The safety and efficacy of RPIID dose was evaluated in phase II stage.Results: In total, 50 patients were enrolled (13 to phase Ib and 37 to phase II). In the first dose-finding cohort (afatinib 40 mg plus nimotuzumab 100 mg), one patient experienced dose-limiting toxicity (DLT) of grade 3 diarrhea and in the subsequent cohort (afatinib 40 mg plus nimotuzumab 200 mg), two DLTs (grade 3 diarrhea and grade 3 neutropenia) occurred in 2 of 6 patients. Accordingly, RPIID was determined as afatinib 40 mg plus nimotuzumab 100 mg. In 44 patients treated with RPIID, 7 (16%) patients had grade 3 toxicities; skin rash (7%), diarrhea (5%), acne (2%), and fatigue (2%). The overall response rate was 23% and the median duration of response was 4.3 months (range, 0.7-16.2 months). The median progression-free survival and overall survival were 4.0 months [95% confidence interval (CI), 2.3-5.7 months] and 11.7 months (95% CI, 9.4-14.0 months), respectively.Conclusions: Combination treatment of afatinib and nimotuzumab demonstrated an acceptable safety profile and encouraging antitumor activity in advanced NSCLC patients with acquired resistance to gefitinib or erlotinib. Larger phase III trial is warranted to confirm its efficacy and safety.

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Section: Introductionmentioning

confidence: 99%

A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non–Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib

Lee

Sun

Lim

et al. 2016

Clinical Cancer Research

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“…These compounds have shown similar efficacy in studies and meta-analysis which indirectly compared them, reaching an efficacy plateau in both PFS (10-12 months) and OS (ranging from 21 to 30 months) (Haspinger et al, 2015). Afatinib is the only compound showing a significant OS benefit in the recent pooled analysis of both LuxLung3 (LL3) and LuxLung6 (LL6) trials, even if limited to the subgroup of patients with EGFR exon 19 deletion (Yang et al, 2015a). Furthermore it is the TKI with more evidence-based activity against EGFR uncommon mutations (Yang et al, 2015c).…”

Section: Indirect Comparisonsmentioning

confidence: 99%

EGFR inhibition in NSCLC: New findings…. and opened questions?

Passiglia

Listì

Castiglia

et al. 2017

Critical Reviews in Oncology/Hematology

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The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent findings regarding EGFR-inhibition in NSCLC, highlighting the current unsolved questions on the selection of the best TKI in first-line, which therapy can be combined with upfront EGFR-TKIs, how to overcome acquired resistance, and which are the clinical applications of liquid biopsy

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“…Patients with Ex19 advanced NSCLC have consistently shown improved outcomes with afatinib vs. chemotherapy compared with those with Ex21 NSCLC (9). The cause for these differences in response to EGFRTKIs among EGFR mutation subtypes is not known.…”

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confidence: 99%

Comment on prognostic value of epidermal growth factor receptor mutation subtypes in surgically resected non-small cell lung cancer

et al. 2017

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Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials

Cited by 1,429 publications

References 26 publications

A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non–Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib

A Phase Ib/II Study of Afatinib in Combination with Nimotuzumab in Non–Small Cell Lung Cancer Patients with Acquired Resistance to Gefitinib or Erlotinib

EGFR inhibition in NSCLC: New findings…. and opened questions?

Comment on prognostic value of epidermal growth factor receptor mutation subtypes in surgically resected non-small cell lung cancer

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