Afatinib treatment in advanced non-small cell lung cancer

Figures & data

Figure 1 Summary of mechanisms underlying resistance to first-generation EGFR-TKIs.

Figure 2 Chemical structure of BIBW 2992 (afatinib).

Table 1 Phase I trials combining afatinib with other anti-cancer agents

Study agents	Patients	n (NSCLC)	DLTs	Phase II afatinib dose	Efficacy results
Afatinib 40 mg daily + cetuximab 250–500 mg/m^2 bi-weekly^Citation43	NSCLC with acquired resistance to EGFR-TKI	26	Nil		In 22 patients receiving afatinib 40 mg + cetuximab 500 mg/m^2; SD 22/22 PR 8/22
Afatinib 20–50 mg daily + paclitaxel 80 mg/m^2 D1, 8, 15 q28^Citation45	Advanced solid tumors expressing EGFR. PS 0-1	16	Mucositis, fatigue	40 mg	PR = 6 (3 NSCLC) SD = 8
Afatinib 10–160 mg D2–4 + docetaxel 75 mg/m^2 q21^Citation46	Advanced solid tumors	40	Neutropenia, nausea, diarrhea	90 mg	PR = 4 CR = 1 SD = 10
Afatinib 20–50 mg daily + vinorelbine 25 mg/m^2 D1, 8, 15, 22 q28^Citation47	Advanced solid tumors, PS 0-1	15 (4)	Mucositis, febrile neutropenia, diarrhea	40 mg	n/a
Afatinib 20–50mg daily + A: cisplatin/paclitaxel q21 B: cisplatin/5FU q21^Citation48	Advanced solid tumors	47	Neutropenic sepsis, elevated AST/ALT, asthenia, mucositis, diarrhea	A; 40 mg B; 30 mg	A; PR = 4 SD = 11 B; CR = 1 PR = 3 SD = 8

Abbreviations: DLT, dose-limiting toxicity; SD, stable disease; PR, partial response; CR, complete response; PS, performance status.

Table 2 Summary of current NCI trials evaluating the role of afatinib in NSCLC³²

Trial	Agents	Location	Design	Participants/schedule	1° endpoint	2° endpoint
LUX-Lung 3 NCT00949650	Afatinib vs cisplatin/pemetrexed as 1st line treatment for lung adenocarcinoma with EGFR mutation	EU, USA, Canada	Randomised Phase III	Stage IIIB/IV adenocarcinoma, EGFR mutation, chemotherapy and EGFR TKI naïve	PFS	RR, OS, HRQOL, safety
LUX-Lung 5 NCT01085136	Afatinib + weekly paclitaxel vs investigator’s choice chemotherapy, following progression on afatinib	Global	Randomised Phase III	Stage IIIB/IV NSCLC, failed EGFR TKI and ≥1 line of chemotherapy	OS	RR, PFS, HRQOL, safety
LUX-Lung 6 NCT01121393	Afatinib vs cisplatin/gemcitabine as 1st line treatment for lung adenocarcinoma with EGFR mutation	China, Korea	Randomised Phase III	Stage IIIB/IV, adenocarcinoma, EGFR mutation, chemotherapy and EGFR TKI naïve	PFS	RR, OS, HRQOL, safety
NCT01003899	Afatinib as 3rd line treatment for lung adenocarcinoma with wild-type EGFR	Korea	Phase II	Stage IIIB/IV, adenocarcinoma, wild-type EGFR, progressed on ≥2 prior chemotherapies	RR	PFS, safety Exploratory biomarkers
NCT00993499	Afatinib + sirolimus in NSCLC with EGFR mutation and/or prior response to erlotinib	Spain	Phase I	Stage IIIB/IV NSCLC with EGFR mutation and/or previous response to erlotinib, failed ≥1 prior chemotherapies	MTD and Phase II dose	Safety, PK analysis, RR
NCT01156545	Afatinib + simvastatin vs afatinib alone for non-adenocarcinoma NSCLC	Korea	Randomised Phase II	Stage IIIB/IV non-adenomatous NSCLC, progressed ≥1 prior chemotherapies	RR	PFS, OS, safety, biomarker analysis

Abbreviations: PFS, progression-free survival; OS, overall survival; RR, response rate; HRQOL, health related quality of life; MTD, maximum tolerated dose.

JanjigianYGroenHHornLActivity and tolerability of afatinib (BIBW 2992) and cetuximab in NSCLC patients with acquired resistance to erlotinib or gefitinib [abstract]J Clin Oncol20112915S7525

 Web of Science ®Google Scholar

AngJMikropoulosCStavridiFA phase I study of daily BIBW 2992, an irreversible EGFR/HER-2 dual kinase inhibitor, in combination with weekly paclitaxel [abstract]J Clin Oncol20092715Se14541

 Google Scholar

AwadaADumezHWolterPA phase I dose finding study of the 3-day administration of BIBW 2992, an irreversible dual EGFR/HER-2 inhibitor, in combination with three-weekly docetaxel in patients with advanced solid tumors [abstract]J Clin Oncol20092715Se3556

 Google Scholar

BahledaRSoriaJBergeYPhase I trial assessing safety and pharmacokinetics of afatinib (BIBW 2992) with intravenous weekly vinorelbine in advanced solid tumors [abstract]J Clin Oncol20112915S2585

 Web of Science ®Google Scholar

VermorkenJMachielsJRotteySThurmHPellingKLahogueAPhase Ib study evaluating the combination of BIBW 2992 with two different standard chemotherapy regimens, cisplatin/paclitaxel (PT) and cisplatin/5-FU (PF), in patients with advanced solid tumors [abstract]J Clin Oncol201028Supple13521

 Google Scholar

Available from: http://www.clinicaltrials.gov.

 Google Scholar