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Y. Shi
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OA23 - EGFR Targeted Therapies in Advanced NSCLC (ID 410)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, S. Lu
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 2
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OA23.05 - First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival Analysis of LUX-Lung 7 (ID 5347)
15:05 - 15:15 | Author(s): Y. Shi
- Abstract
- Presentation
Background:
The irreversible ErbB family blocker afatinib and the reversible EGFR TKI gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus gefitinib in this setting.
Methods:
LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients with stage IIIb/IV NSCLC harbouring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade ≥3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after ~250 PFS events. The primary OS analysis was planned after ~213 OS events and a follow-up period of ≥32 months.
Results:
319 patients were randomised (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p=0.017), TTF (0.73 [0.58‒0.92], p=0.007) and ORR (70 vs 56%, p=0.008) were significantly improved with afatinib versus gefitinib. The most common grade ≥3 AEs were diarrhoea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had ≥1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs ≥40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drug-related grade ≥3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had ≥1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting.
Conclusion:
Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drug-related AEs without compromising efficacy. Primary OS analysis will be reported.
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-003 - ROS1 (D4D6) is Reliable for Immunohisochemistry Detecting of ROS1 Fusion Lung Adenocarcinoma in Malignant Pleural Effusion (ID 3841)
14:30 - 14:30 | Author(s): Y. Shi
- Abstract
Background:
ROS1 fusion is of a low frequency genetic alteration in non-small cell lung cancer (NSCLC). The clinical trial showed that NSCLC patients harboring ROS1 fusion could benefit from crizotinib treatment. Several studies reported that immunohistochemistry (IHC) could be employed as a screening method for detecting ROS1 fusion in tumor tissue using Anti-ROS1(D4D6) antibody. Malignant pleural effusion (MPE) is the common sample type in advanced NSCLC, the reliability of ROS1(D4D6) for detecting ROS1 fusion in MPE cell blocks (CBs) should be explored.
Methods:
Anti-ROS1(D4D6) monoclonal antibody (Cell Signaling Technology, Danvers, USA) IHC testing was performed on 227 formalin fixed paraffin embedded (FFPE) MPE CBs from lung adenocarcinoma patients. RT-PCR using ROS1 fusion gene detection kit (AmoyDx) was performed to detected ROS1 gene fusion as a comfirming test. Some other lung cancer driver genes were also detected in both IHC/RT-PCR ROS1 positive samples, among which EGFR, KRAS, BRAF, PIK3CA and HER2 20 exon mutation was tested by amplification refractory mutation system kits(AmoyDx), ALK and RET fusion was tested by RT-PCR kits(AmoyDx).
Results:
4 of 227 MPE samples(1.76%) of lung adenocarcinoma were interpreted as ROS1 fusion-positive cases by IHC staining, and the cytoplasmic and membranous granular positive signals were displayed. Comparison with RT-PCR testing results, 3 of 4 IHC positive cases were verified by RT-PCR, the sensitivity was 100% and specificity of was 99.6%. The clinicopathologic features and other genes status of 3 both IHC/RT-PCR positive patients were showed Table 1. One ROS1 IHC/RT-PCR positive lung adenocarcinoma patient received crizotinib therapy and obtained partial response.
Conclusion:
ROS1 (D4D6) would be a reliable antibody for screening ROS1 fusion-positive lung adenocarcinoma on FFPE MPE CBs by IHC assay and shows high specificity in the FFPE MPE CBs samples .Table 1 Clinicopathologic features and genes status of ROS1 IHC/RT-PCR positive patients
E/K/B/P/H: EGFR/KRAS/BRAF/PIK3CA/HER-2 20 exon mutation, A/R: ALK/RET fusion, WT: wild type, PEM+CIS: Pemetrexed plus Cisplatin,PR: partial response, m: monthsGender Age Smoking TTF1/ P63 E/k/B/ P/H A/R Therapy Efficacy PFS/Follow -up p1 Male 55 Smoker +/- WT WT crizotinib PR 10m+/alive p2 Female 60 Never +/- WT WT No 1m/Dead P3 Male 62 Never +/- WT WT PEM+CIS PR 9m+/alive
