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Targeted therapies and management of brain metastasis (ID 40)
- Event: ELCC 2017
- Type: Proffered Paper session
- Presentations: 1
86O - Afatinib (A) plus cetuximab (C) in the treatment of patients (pts) with NSCLC: The story so far (ID 311)
16:45 - 18:15 | Author(s): E. Smit
Constitutive EGFR signalling due to activating mutations (e.g. EGFRm+ NSCLC) or overexpression (e.g. squamous (sq) NSCLC) is a common mechanism of tumourigenesis. There is biological rationale for combining A + C in tumours with unmet medical need, e.g. EGFRm+ NSCLC with resistance to EGFR-TKIs, and in advanced sqNSCLC. Preclinically, A + C improved anti-tumour activity in EGFRm+ NSCLC vs A or C alone. Here we report outcomes from two Phase Ib studies of A + C: NCT01090011 (study 1) in pts with EGFRm+ NSCLC resistant to gefitinib/erlotinib (G/E); and NCT02020577 (study 2) in unselected pts with heavily pretreated advanced solid tumours, including sqNSCLC.
Study 1 comprised a dose-finding phase to identify the maximum tolerated dose (MTD) of A + C, and an expansion phase (EP) in which 126 pts received the MTD of A 40 mg/day + C 500 mg/m Q2W. In study 2, 9 pts received A + C in a dose-escalation phase, and a further 49 pts received the MTD of A 40 mg/day + C 250 mg/m/week in an EP, including 12 pts with sqNSCLC.
Drug-related adverse events (DR-AEs; all grades) were reported in 99% of pts in the EP of study 1 (n = 126), and 98% of pts in study 2 (n = 58). Grade 3/4/5 DR-AEs were experienced by 44%/2%/2% of pts in study 1 and 31%/3%/0% in study 2. DR-AEs led to discontinuation of treatment in 14% of pts in study 1 and 12% in study 2. Efficacy in pts with NSCLC is shown in the table. In the study 1 EP, ORR was 29% and median PFS was 4.7 months; there were no significant differences in ORR or median PFS in pts with T790M+ vs T790M- tumours (32 vs 25% [p = 0.341] and 4.6 vs 4.8 months [p = 0.643], respectively). Median duration of OR was 5.7 months. In the study 2 EP, 75% of pts with sqNSCLC had SD, and median PFS was 11.9 weeks.
Based on the demonstrated antitumour activity and a predictable/manageable safety profile, A + C may be a treatment option in pts with EGFRm+ NSCLC and acquired resistance to G/E (irrespective of T790M status) or with pre-treated advanced sqNSCLC. rnTable: 86OEfficacy outcomesrn
rnrnCR, complete response; PR, partial response; SD, stable disease; PD, progressive disease;rnOR, objective response; PFS, progression-free survival 1. Janjigian YY, et al. Cancer Discov 2014;4:1036-45 2. Gazzah A, et al. Eur J Cancer 2016;68(Suppl. 1);S139:abstract 426rn
rnrn Trialrn EGFRm+ NSCLCrn sqNSCLCrn rnrnrn Study 1 expansion phase (n = 126)rn Study 2 expansion cohort (n = 12)rn rnrn Disease control (CR/PR/SD), n (%)rn 89 (71)rn 9 (75)rn rnrn OR (CR/PR), n (%)rn 37 (29)rn 0rn rnrn SDrn 52 (41)rn 9 (75)rn rnrn Unconfirmed ORrn 5 (4)rn –rn rnrn PD, n (%)rn 27 (21)rn 3 (25)rn rnrn Median duration of OR, months (range)rn 5.7 (1.8–24.4)rn –rn rnrn Median duration of disease control, weeks (standard deviation)rn –rn 17.9 (9.9)rn rnrnrn Median PFS (95% CI)rn 4.7 months (4.3–6.4)rn 11.9 weeks (5.1–19.4)rn
Clinical trial identification:
NIH study numbers: 1200.71: NCT01090011 1200.122: NCT02020577
Legal entity responsible for the study:
J-C. Soria: Astrazeneca, Astex, GSK, Gammamabs, Eli Lilly, MSD, Merus, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Symphogen, Takeda. Y.Y. Janjigian: Employee of Memorial Sloan Kettering Cancer Center Advisory boards: ASCO GI Corporate-sponsored research: Merck, BMS Consultant: Pfizer Grant/research: BI, Bayer, Amgen, Genentech, Roche. H.J.M. Groen: Participated on advisory boards for Boehringer Ingelheim. W. Pao: Reports that patent rights on EGFR T790M were licensed by MSKCC to Molecular MD. J. Fan: Boehringer Ingelheim employee. M. Ould-Kaci: Employee of Boehringer Ingelheim. L. Horn: Consulting for AbbVie, BMS, Merck, Eli Lilly, Xcovery, Bayer. All other authors have declared no conflicts of interest.