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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe subgroup of patients with the \u003Cem\u003EEGFR\u003C\/em\u003E-activating mutation in exon 19 or 21 appeared to have a favorable trend for dacomitinib vs erlotinib in progression-free survival. Afatinib was favored over erlotinib for second-line treatment of advanced squamous cell carcinoma in terms of progression-free survival, overall response rate, and disease control rate.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Edacomitinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eerlotinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eafatinib\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Etyrosine kinase inhibitor\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Enon\u2013small cell lung cancer\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eprogression-free survival\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EARCHER 1009\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELUX-8 Lung\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Edrug therapy\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEGFR\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Esquamous cell carcinoma\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eoncology clinical trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ehead \u0026amp; neck cancers\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EResults of 2 trials comparing erlotinib, a first-generation reversible tyrosine kinase inhibitor, with second-generation irreversible tyrosine kinase inhibitors (dacomitinib and afatinib) in patients with either advanced non\u2013small cell lung cancer (NSCLC) or squamous cell carcinoma (SCC) were presented in one session.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EEGFR Mutant Subset Analysis of ARCHER 1009 Comparing Dacomitinib and Erlotinib\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EThe ARCHER 1009 trial was a randomized, double-blind, phase 3 study in which patients (n\u2005=\u2005878) with locally advanced or metastatic NSCLC who had progressed after 1 to 2 prior lines of therapy were randomized 1:1 to receive either dacomitinib 45 mg\/d or erlotinib 150 mg\/d. Among these patients, 47 treated with dacomitinib and 44 treated with erlotinib had \u003Cem\u003EEGFR\u003C\/em\u003E-mutant NSCLC, and 37 treated with dacomitinib and 39 treated with erlotinib had an \u003Cem\u003EEGFR\u003C\/em\u003E-activating mutation in exon 19 or 21.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EIt has been previously reported that for the overall study population, dacomitinib was not superior to erlotinib for patients with advanced NSCLC or in patients with \u003Cem\u003EKRAS\u003C\/em\u003E wild-type tumors [Ramalingam SS et al. \u003Cem\u003ELancet Oncol.\u003C\/em\u003E 2014]. In the present session, Luis Paz-Ares, MD, PhD, Hospital Universitario Virgen del Rocio, Seville, Spain, discussed a subset analysis of patients with \u003Cem\u003EEGFR\u003C\/em\u003E-activating mutations [Paz-Ares L et al. \u003Cem\u003EAnn Oncol.\u003C\/em\u003E 2015].\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EAmong the 91 patients with \u003Cem\u003EEGFR\u003C\/em\u003E mutations, the median progression-free survival (PFS) per independent review was 11.1 months (95% CI, 5.6 to 21.9) with dacomitinib and 10 months (95% CI, 7.4 to 16.6) with erlotinib (HR, 0.935; 95% CI, 0.539 to 1.624; one-sided \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.403). Among the 76 patients with \u003Cem\u003EEGFR\u003C\/em\u003E-activating mutations in exon 19 or 21, the median PFS per independent review was 14.6 months (95% CI, 7.6 to not reached [NR]) with dacomitinib and 9.6 months (95% CI, 7.3 to 16.6) with erlotinib (HR, 0.707; 95% CI, 0.380 to 1.315; one-sided \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.136). Notably, the PFS values per independent review were not mature, as the event rate was 56%.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EWhen PFS was determined per investigator\u2019s assessment, the median PFS for all \u003Cem\u003EEGFR\u003C\/em\u003E mutations was 10.9 months for patients treated with dacomitinib (95% CI, 7.5 to 18.2) and 10 months for patients treated with erlotinib (95% CI, 7.4 to 12.8), with an HR of 0.874 (95% CI, 0.542 to 1.408; one-sided \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.286). Among the 76 patients with \u003Cem\u003EEGFR\u003C\/em\u003E-activating mutations in exon 19 or 21, the median PFS per investigator\u2019s assessment was 13.4 months (95% CI, 9.0 to 19.6) with dacomitinib and 10.0 months (95% CI, 7.4 to 12.8) with erlotinib (HR, 0.749; 95% CI, 0.440 to 1.275; one-sided \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.142). The PFS data by the investigator\u2019s assessment were mature.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EFor patients with \u003Cem\u003EEGFR\u003C\/em\u003E mutations, overall survival (OS) was 26.6 months (95% CI, 21.6 to NR) with dacomitinib and 28.0 months (95% CI, 16.4 to NR) with erlotinib (HR, 0.976; 95% CI, 0.534 to 1.786; one-sided \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.472). For patients with \u003Cem\u003EEGFR-\u003C\/em\u003Eactivating mutations in exon 19 or 21, OS was 26.6 months (95% CI, 21.6 to NR) with dacomitinib and 23.2 months (95% CI, 16.0 to NR) with erlotinib (HR, 0.796; 95% CI, 0.405 to 1.565; one-sided \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.256). These OS data were not mature as the trial was still \u0026lt;\u200550% deaths. The toxicity profile was similar between the \u003Cem\u003EEGFR\u003C\/em\u003E mutation population and the overall patient population.\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EOverall, the subgroup of patients with the \u003Cem\u003EEGFR-\u003C\/em\u003Eactivating mutation in exon 19 or 21 appeared to show a trend in favor of dacomitinib for PFS. The activity of dacomitinib in NSCLC with \u003Cem\u003EEGFR\u003C\/em\u003E-activating mutations as a second- and third-line treatment is being reviewed for future presentation.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003ELUX-Lung 8: Afatinib vs Erlotinib for Squamous Cell Carcinoma\u003C\/h2\u003E\n         \u003Cp id=\u0022p-9\u0022\u003EAfatinib has shown activity in patients with SCC of the head\/neck and lung. Silvia Novello, MD, PhD, San Luigi Hospital, Orbassano, Italy, discussed the results of the LUX-Lung 8 phase 3 trial [Goss GD et al. \u003Cem\u003EAnn Oncol.\u003C\/em\u003E 2015], based on a poster by Glendwood D. Goss, MD, University of Ottawa, Ottawa, Canada, and colleagues. The LUX-Lung 8 trial prospectively compared afatinib and erlotinib in patients with SCC of the lung after failure of platinum-based first-line chemotherapy. Prof Novello explained that early trial data led researchers to expect that afatinib would have a different efficacy, safety profile, pharmacokinetic interactions, and activity in different mutations, as well as a specific role in overcoming resistance and ability to target other receptors, but not all of the above-mentioned characteristics have been clinically demonstrated.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EIn the LUX-Lung 8 trial, patients with stage IIIB\/IV SCC were randomized 1:1, after being stratified by race to avert any possible imbalance in \u003Cem\u003EEGFR\u003C\/em\u003E mutation. The primary analysis was based on 414 PFS events when 669 patients had been randomized (afatinib n\u2005=\u2005335; erlotinib n\u2005=\u2005334).\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003EThe median PFS was significantly higher for afatinib vs erlotinib (2.4 months vs 1.9 months; HR, 0.822; 95% CI, 0.676 to 0.998; log-rank \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.043). Novello noted that an HR of 0.822 is much less than that required by recent American Society of Clinical Oncology guidelines that define clinically meaningful outcomes [Ellis LM et al. \u003Cem\u003EJ Clin Oncol\u003C\/em\u003E. 2014], but she raised the question of how to meet that goal in SCC.\u003C\/p\u003E\n         \u003Cp id=\u0022p-12\u0022\u003EThe overall response rate (4.8% vs 3%; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.23) and disease control rate (45.7% vs 36.8%; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.02) were higher with afatinib vs erlotinib.\u003C\/p\u003E\n         \u003Cp id=\u0022p-13\u0022\u003EThe overall adverse event (AE) profiles were similar, with grade 3 or higher AEs occurring in 50.2% of patients receiving afatinib and in 49.1% of patients receiving erlotinib. Afatinib had a higher incidence of drug-related grade 3 or higher diarrhea (9.7% vs 2.4%) and grade 3 stomatitis (3.3% vs 0%), while erlotinib had a higher incidence of grade 3 rash\/acne (5.5% vs 9%). The drug was discontinued due to AEs in 8.8% of the afatinib arm and 4.2% of the erlotinib arm.\u003C\/p\u003E\n         \u003Cp id=\u0022p-14\u0022\u003ENotably, Prof Novello stated that the toxicity was not negligible. At 2 months, 50% of the patients did not benefit from one treatment vs the other. This raises the question of how to select patients who can really benefit from treatment.\u003C\/p\u003E\n         \u003Cp id=\u0022p-15\u0022\u003EMore patients had improved global health status (36.4% vs 27.1%; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.03) and cough (44% vs 33%; \u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.01) with afatinib than with erlotinib. Changes in mean scores over time favored afatinib over erlotinib for cough, dyspnea, and physical and role functioning.\u003C\/p\u003E\n         \u003Cp id=\u0022p-16\u0022\u003EOverall, LUX-Lung 8 is the largest prospective trial comparing afatinib vs erlotinib in patients with relapsed\/refractory SCC. PFS, tumor shrinkage, overall response rate, and disease control rate were significantly better for afatinib than erlotinib. Afatinib had drug-related AEs more frequently and severely than erlotinib, but rates of discontinuation from AEs were comparable. Notably, this trial was still recruiting when this data analysis occurred.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/15\/8\/5.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzl1bq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}