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M. Sebastian
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-075 - Afatinib Dose Adjustment: Effect on Safety, Efficacy and Patient-Reported Outcomes in the LUX-Lung 3/6 Trials in EGFRm+ NSCLC (ID 9365)
09:30 - 09:30 | Author(s): M. Sebastian
- Abstract
Background:
Afatinib 40mg/day is approved globally for first-line treatment of EGFR mutation-positive (EGFRm+) NSCLC. Afatinib is available in several tablet strengths (20/30/40/50mg), and tolerability-guided dose adjustment schemes are well established. Here, we evaluate the impact of afatinib dose reduction on safety (AEs), pharmacokinetics, PFS and patient-reported outcomes (PROs) in the Phase III LUX-Lung (LL) 3 and 6 trials.
Method:
Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC in LL3/6 received either 40mg/day afatinib or chemotherapy. In case of any treatment-related grade ≥3 AEs or selected prolonged grade 2 AEs, afatinib dose was reduced by 10mg decrements (minimum dose 20mg/day). In this post-hoc analysis of all afatinib-treated patients in LL3/6 (n=229/n=239), we compared incidence and severity of common AEs before and after dose reduction, afatinib plasma concentrations in patients who reduced to 30mg versus those remaining on 40mg, and PFS in patients with/without dose reductions in the first 6 months of treatment. PROs were measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire and the EQ-5D™ health status self-assessment questionnaire, and pooled data from both trials were assessed before/after dose reduction; these included scores on the EORTC Global Health/Quality of Life scale (GH/QoL; 0–100), EORTC Performance Functioning scale (PF; 0–100), EQ Visual Analogue Scale (VAS; 0–100) and EQ-5D UK utility scale (EQ UK utility; 0–1).
Result:
Dose reductions occurred in 122/229 (53.3%) patients in LL3 and 67/239 (28.0%) in LL6; >80% of dose reductions occurred in the first 6 months of treatment. Dose reductions decreased the incidence of treatment-related AEs (grade ≥3 AEs before/after dose reduction: LL3, 73%/20%; LL6, 81%/12%), and were more likely among patients who had higher afatinib plasma concentrations prior to subsequent dose reduction (Day 22). On Day 43, geometric mean afatinib plasma concentrations were comparable between patients who had dose reduced (n=59; 23.3ng/mL) and patients who remained on 40mg (n=284; 22.8ng/mL). Median PFS was comparable between patients with or without dose reductions in the first 6 months (LL3: 11.3 versus 11.0 months; HR [95% CI] 1.25 [0.91–1.72]; p=0.175; LL6: 12.3 versus 11.0 months; 1.00 [0.69–1.46]; p=0.982). There were no clinically meaningful changes in PROs following afatinib dose reduction: GH (40/30mg: 59.1/66.9; n=136); PF (79.4/83.0; n=136); EQ VAS (70.1/75.1; n=135); EQ UK utility (0.70/0.78; n=135).
Conclusion:
Tolerability-guided dose adjustments effectively reduced afatinib-related AEs without negatively affecting therapeutic efficacy and PROs.
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P3.01-088 - Molecular Testing and First-Line Treatment of Patients with NSCLC. First Results from the German CRISP Study (AIO-TRK-0315) (ID 9960)
09:30 - 09:30 | Presenting Author(s): M. Sebastian
- Abstract
Background:
Treatment of non-small cell lung cancer (NSCLC) is quickly evolving. New biomarkers and targeted agents have been approved at a rapid pace. It is of high interest to patients, physicians and reimbursement institutions to investigate molecular testing and subsequent treatment decisions in routine practice.
Method:
The prospective, national clinical research platform CRISP recruits patients in up to 150 cancer centres in all therapeutic sectors in Germany. Patients will be followed until death or for a maximum of 3 years. Raw data from 717 patients recruited by 78 centers by April 03[rd] was analysed regarding molecular testing and 1[st]-line treatment.
Result:
Data on histology was available for 635 patients, 71% non-squamous carcinoma (nsqc), 18% squamous carcinoma (sqc). Median age was 67 years and 61% of patients were male. 11% of patients were never smokers. In patients with nsqc (n=507) molecular test rates for EGFR, ALK, ROS-1 and PD-L1 were 69%, 65%, 51% and 26%, respectively. The overall PD-L1 test rate (nsqc & sqc) was 21% in 2016 and has been 27% so far in 2017. Of patients for whom test results were available at time of analysis 58% (n=87) were PD-L1 positive (nsqc 60%, n=76 and sqc 46%, n=11). An EGFR alteration was detected in 16% (n=57), an ALK alteration in 8% (n=25), and a ROS-1 alteration in 4% (n=9) of nsqc patients. Overall, 53% of patients received a carboplatin-based, 22% a cisplatin-based, and 7% a platin-free chemotherapy, while 14% received targeted and 4% other (experimental) therapies. Patients with EGFR alterations (n=57) were most frequently treated with 1[st]-line afatinib (33%), erlotinib (12%), or gefitinib (11%). Patients with ALK alterations (n=25) were most frequently treated with 1[st]-line crizotinib (48%). Patients with PD-L1 positive tumours were most frequently treated with platinum based doublet therapies (carboplatin combined with gemcitabine/taxane/pemetrexed or cisplatin combined with pemetrexed) or with pembrolizumab. The use of 1[st]-line pembrolizumab increased from 7% to 16% from 2016 to 2017. An update with data collected until October 2017 (>1,100 patients expected) will be presented.
Conclusion:
For the first time, CRISP presents real life data from all therapeutic sectors in Germany. Patients are frequently tested for molecular alterations and more than half of the patients with molecular alterations can start 1[st]-line treatment with a targeted therapy. Supported by AstraZeneca, Boehringer Ingelheim, BMS, Celgene, Lilly, MSD, Novartis, Pfizer and Roche.
