Afatinib versus gemcitabine/cisplatin for first-line treatment of Chinese patients with advanced non-small-cell lung cancer harboring EGFR mutations: subgroup analysis of the LUX-Lung 6 trial

Yi-Long Wu, Chong-Rui Xu, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Jian Hua Shi, Angela Märten, Jean Fan, Barbara Peil, Caicun Zhou, Yi-Long Wu, Chong-Rui Xu, Cheng-Ping Hu, Jifeng Feng, Shun Lu, Yunchao Huang, Wei Li, Mei Hou, Jian Hua Shi, Angela Märten, Jean Fan, Barbara Peil, Caicun Zhou

Abstract

Introduction: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in China. Four epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors - afatinib, erlotinib, icotinib, and gefitinib - are available for first-line treatment of NSCLC in China; however, there are few data to guide treatment choice. The Phase III LUX-Lung 6 trial compared afatinib with platinum-based chemotherapy for first-line treatment of patients from Southeast Asia with EGFR mutation-positive advanced NSCLC. This post hoc analysis assessed the findings from LUX-Lung 6 in Chinese patients.

Clinical trial registration: ClinicalTrials.gov: NCT01121393.

Materials and methods: Previously untreated patients with EGFR mutation-positive stage IIIB/IV lung adenocarcinoma were randomized 2:1 to receive afatinib or ≤6 cycles of gemcitabine/ cisplatin. The key outcomes were progression-free survival (PFS; primary), objective response rate, disease control rate, overall survival (OS), duration of response and disease control, patient-reported outcomes, and safety. Three hundred and twenty-seven patients from mainland China were treated (89.8% of overall LUX-Lung 6 population; afatinib 217, gemcitabine/cisplatin 110).

Results: PFS was significantly longer with afatinib than gemcitabine/cisplatin (median 11.0 versus 5.6 months; hazard ratio [HR], 0.30 [95% CI, 0.21, 0.43]; P,0.0001). Overall, there was no significant difference in OS between treatment arms; however, in a subgroup analysis, afatinib significantly improved OS versus gemcitabine/cisplatin in patients with an EGFR Del19 mutation (median 31.6 versus 16.3 months; HR, 0.61 [95% CI, 0.41, 0.91]; P=0.0146). Afatinib was well tolerated, with most treatment-related adverse events (TRAEs) being of grade 1 or 2 severity. The most common grade 3/4 TRAEs with afatinib were rash/acne (15.9%/0.5%), stomatitis (6.1%/0%), and diarrhea (5.6%/0%). TRAEs leading to permanent discontinuation were reported in 12 patients (5.6%) receiving afatinib and 43 (41.7%) receiving gemcitabine/cisplatin. Afatinib significantly improved PFS compared with standard first-line chemotherapy in Chinese patients with EGFR mutation-positive NSCLC and demonstrated a manageable safety profile.

Conclusion: The findings support the rationale for using afatinib as a first-line treatment option for this patient population.

Keywords: Chinese patients; EGFR; NSCLC; Phase III; afatinib; first-line.

Conflict of interest statement

Disclosure Y-LW reports consultancy fees from AstraZeneca; and lecture fees from AstraZeneca, Eli Lilly, Pfizer, Roche, and Sanofi. CZ reports lecture fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Roche, and Sanofi. AM, JF, and BP report employment by Boehringer Ingelheim. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Dose adjustments among Chinese patients who were LTRs to afatinib. Abbreviation: LTRs, long-term responders.
Figure 2
Figure 2
(A) PFS in Chinese patients receiving afatinib and gemcitabine/cisplatin (independent review) and (B) forest plot of PFS for subgroups of special interest (independent review). Abbreviations: Cis, cisplatin; ECOG, Eastern Cooperative Oncology Group; EGFR, epidermal growth factor receptor; Gem, gemcitabine; PFS, progression-free survival.
Figure 3
Figure 3
OS (A) in all Chinese patients in LUX-Lung 6, (B) in Chinese patients with Del19 mutations, and (C) in Chinese patients with the L858R mutation. Abbreviations: Cis, cisplatin; Gem, gemcitabine; OS, overall survival.
Figure 4
Figure 4
Percentage of patients who had improvements in cough, dyspnea, and pain. Outcomes assessed according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (QLQ-C30) and its lung cancer-specific module (QLQ-LC13). Abbreviations: Cis, cisplatin; Gem, gemcitabine.

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