Clinical and comparative utility of afatinib in non-small cell lung cancer

Figures & data

Table 1 LUX-Lung clinical development program

LUX-Lung study	Phase	Enrollment (patients, n)	Treatment	Target population	Primary end point
1	IIb/III	585	Afatinib vs placebo	1–2 CT lines and erlotinib/gefitinib-resistant	OS
2	II	129	Afatinib	EGFR mut+, 0–1 prior CT line	RR
3	III	330	Afatinib vs CDDP + PEM	EGFR mut+, treatment naïve	PFS
4	I/II	72	Afatinib	1–2 CT lines and erlotinib/gefitinib-resistant	Phase I: safety Phase II: RR
5	III	1,155	Afatinib + TXL vs CT	Erlotinib/gefitinib-resistant, afatinib-resistant	PFS
6	III	364	Afatinib vs CDDP + Gem	EGFR mut+, treatment naïve	PFS
7	IIb	316	Afatinib vs gefitinib	EGFR mut+, treatment naïve	PFS, TTP, OS
8	III	800	Afatinib vs erlotinib	1 prior CT line, SqCC histology	PFS

Abbreviations: CDDP, cisplatin; CT, chemotherapy; EGFR mut+, epidermal growth factor mutation positive; Gem, gemcitabine; OS, overall survival; PEM, pemetrexed; PFS, progression-free survival; RR, response rate; SqCC, squamous cell carcinoma; TTP, time to progression; TXL, paclitaxel.

Figure 1 Afatinib chemical structure.

Table 2 Afatinib in patients with uncommon EGFR mutations in the LUX-Lung 2, 3, and 6 trials²⁷

EGFR mutation	Patients (n)	RR (%)	PFS (months)	OS (months)
Exon 19 del +	308	60.8	13.6	NR
Exon 21 point mut
Exon 20 insertion	20	8.7	2.7	9.4
De novo T790M	14	14.3	2.9	14.9
G719X (exon 18)	18	78.0	13.8	26.9
L861Q (exon 20)	16	56.0	8.2	16.9
S768I (exon 21)	5	100	14.7	NR

Abbreviations: del, deletion; EGFR, epidermal growth factor; mut, mutation; n, number; NR, not reported; PFS, progression free survival; OS, overall survival; RR, response rate.

Table 3 Toxicity profile in the major Phase III clinical trials of afatinib, erlotinib, and gefitinib

	LUX-Lung 1^Citation30 (Afatinib 50 mg)		LUX-Lung 3^Citation24 (Afatinib 40 mg)		LUX-Lung 6^Citation25 (Afatinib 40 mg)		EURTAC^Citation8 (Erlotinib 150 mg)		IPASS^Citation3 (Gefitinib 250 mg)
	All	≥ Grade 3	All	≥ Grade 3	All	≥ Grade 3	All	≥ Grade 3	All	≥ Grade 3
Diarrhea	87%	17%	96%	15%	90%	6%	57%	5%	47%	4%
Rash/acne	78%	14%	90%	16%	81%	15%	80%	13%	66%	3%
Stomatitis/mucositis	61%	3%	73%	9%	52%	5%	NR	NR	17%	0
Paronychia	39%	5%	57%	11%	33%	0%	NR	NR	14%	0
Decreased appetite	31%	4%	29%	4%	16%	3%	31%	0	22%	2%
Nausea	23%	2%	25%	1%	12%	0%	NR	NR	17%	0
Fatigue	29%	6%	27%	3%	17%	2%	57%	6%	17%	0
Vomiting	20%	2%	23%	4%	13%	1%	NR	NR	13%	0

Abbreviations: NR, not reported; EURTAC, European Erlotinib versus chemotherapy trial; IPASS, Iressa Pan Asia Study.

YangJC-HSequistLVGeaterSLActivity of afatinib in uncommon epidermal growth factor receptor (EGFR) mutations: findings from three trials of afatinib in EGFR mutation-positive lung cancerOral presentation at: World Congress on Lung CancerOctober 27–31, 2013Sydney, Australia

 Google Scholar

MillerVAHirshVCadranelJAfatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trialLancet Oncol201213552853822452896

 PubMed Web of Science ®Google Scholar

SequistLVYangJCYamamotoNPhase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutationsJ Clin Oncol201331273327333423816960

 PubMed Web of Science ®Google Scholar

WuYLZhouCHuCPLUX-Lung 6: a randomized, open-label, phase III study of afatinib (A) versus gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lungJ Clin Oncol201331Suppl abst 8016

 Google Scholar

RosellRCarcerenyEGervaisRErlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutations-positive non-small cell lung cancer (EURTAC) a multicenter, open-label, randomized phase 3 trial. Results of the European Erlotinib Versus Chemotherapy (EURTAC) phase III randomized trialLancet Oncol201213323924622285168

 PubMed Web of Science ®Google Scholar

MokTSWuYLThongprasertSGefitinib or carboplatin-paclitaxel in pulmonary adenocarcinomaN Engl J Med200936194795719692680

 PubMed Web of Science ®Google Scholar