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Frank Griesinger
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-013 - Patient-Reported Outcomes and Safety from the Phase III ALUR Study of Alectinib vs Chemotherapy in Pre-Treated ALK+ NSCLC (ID 9007)
09:30 - 09:30 | Author(s): Frank Griesinger
- Abstract
Background:
Alectinib demonstrated superior efficacy versus chemotherapy in ALK+ NSCLC after crizotinib failure (ALUR; NCT02604342). We present PROs and safety in the ITT population and in patients with baseline CNS disease (C-ITT).
Method:
Patients (n=107) with pre-treated ALK+ NSCLC (randomised 2:1) received alectinib (600mg BID) or chemotherapy (pemetrexed 500mg/m[2] or docetaxel 75mg/m[2] q3w) until PD/death/withdrawal. Primary endpoint: investigator-assessed PFS. Secondary endpoints: safety and PROs. Symptoms, functioning, and HRQoL were reported using questionnaires: EORTC QLQ-C30; lung module QLQ-LC13; BN-20 (3 items, CNS symptoms). Pre-specified endpoints included time-to-deterioration (TTD) in lung cancer symptoms, longitudinal analyses of mean score changes from baseline, proportion of patients with clinically meaningful change (≥10-point change from baseline) during treatment.
Result:
High compliance with assessment completion (alectinib 91.7%, chemotherapy 88.6% at baseline); compliance remained ≥70% with alectinib, and decreased with chemotherapy (64.3%, Week 6; ≤70% thereafter). Deterioration of patient-reported fatigue (median TTD 2.7 vs 1.4 months) and arm/shoulder pain (median TTD 8.1 vs 1.9 months) was delayed with alectinib versus chemotherapy. Median TTD in composite symptom endpoint (cough, dyspnoea, chest-pain) was similar between arms. Alectinib patients reported improvement in lung cancer symptoms from baseline (least square [LS] mean) during treatment: fatigue (-6.2), single-item dyspnoea (-6.0), multi-item dyspnoea scale (-2.3), coughing (-4.9), chest pain (-4.2), pain in other parts (-5.3). More patients reported improvement in baseline symptoms (nausea/vomiting, diarrhoea, peripheral neuropathy) with alectinib versus chemotherapy, except constipation. More alectinib patients reported improvements in cognitive function versus chemotherapy (ITT 19% vs 3%; C-ITT 24% vs 4%); average change from baseline in cognitive function favoured alectinib (LS means difference 10.0, 95% CI 2.2–17.7). Median treatment duration: 20.1 weeks alectinib (95% CI 0.4–8.2), 6 weeks chemotherapy (95% CI 1.9–47.1). For alectinib versus chemotherapy: AEs leading to discontinuation, 5.7% vs 8.8%; dose reductions, 4.3% vs 11.8%; dose interruptions due to AEs, 18.3% vs 8.8%. AEs: 77.1% alectinib (grade 3–5, 27.1%); 85.3% chemotherapy (grade 3–5, 41.2%); one fatal AE (chemotherapy); grade ≥3 AEs: 41.2% chemotherapy versus 27.1% alectinib. TEAEs occurring in ≥10% patients: constipation (alectinib 18.6%, all grade 1–2; chemotherapy 8.8% [grade ≥3 2.9%]), nausea (alectinib 1.4%, all grade 1–2; chemotherapy 17.6% [grade ≥3 2.9%]) and fatigue (alectinib 5.7%, all grade 1–2; chemotherapy 26.5% [grade ≥3 8.8%]).
Conclusion:
Alectinib improved HRQoL, functioning, and symptom burden versus chemotherapy (except constipation). Safety of alectinib compared favourably to chemotherapy. Alectinib patients (ITT and C-ITT populations) derived benefit versus chemotherapy.
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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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P3.01-038 - Impact on OS and PFS of 2nd and 3rd Generation TKI in EGFR Mt+ and ALK+ Patients: Results of the NOWEL Network (ID 9338)
09:30 - 09:30 | Author(s): Frank Griesinger
- Abstract
Background:
EGFR TKI treatment is standard of care in patients with metastasized NSCLC carrying an activating EGFR mutation. Targeted therapies achieve a higher ORR, OS, PFS and a better quality of life than chemotherapy. With the advent of 2[nd] and 3[rd] generation TKI´s effective in 1[st] generation TKI resistant tumors, we wanted to study the impact of these drugs on the outcome of patients in a real life setting in 3 lung cancer centers.
Method:
1473 patients from three cancer centers diagnosed with non-squamous cell NSCLC stage IV (UICC 7) were examined. Methods for the mutation testing was performed according to the German Oncopedia guidelines using either Sanger Sequencing or COBAS ® or Next Generation Sequencing.
Result:
964/1473 (65%) consecutive patients with non-squamous cell NSCLC were studied for the presence of tumor mutations. The EGFR mutation rate was 16% (147/943), and the ALK-translocation rate 4% (26/695). Median OS in EGFR mt+ patients was 27 months (n=147) compared to 11 months (n=796) in patients with EGFR WT (p<0.000). Median OS in EGFR mt+ patients depending on the center was 27 (n=95) vs. 28 (n=38) vs. 16 (n=14) months respectively (center 1 vs. center 2 vs. center 3). Median OS in ALK mt+ patients was 24 months (n=19) in center 1 and 11 months (n=5) in center 2 (p<0.025). The ORR in the CR/PR group was 54.2% for patients treated with chemotherapy and 77% for patients treated with TKI on 1[st] line therapy. The chance to reach a CR/PR is 2.83 higher for patients on TKI than for patients on chemotherapy (p<0.02). The use of 3[rd] generation TKI Osimertinib (n=19) lead to a significantly higher OS (n=19, median OS 67 months) than the use of only 1[st] and 2[nd] generation TKI (n=119, median OS 23 months, p<0.000). The hazard ratio for patients treated without Osimertinib was 4.66 [95% CI 2.006-10.81] (p<0.000). Patients treated with 3[rd] gen TKI had significantly longer PFS (11 months, n=7) than patients treated without (5 months, n=20) (p<0.037). Similarly, use of 2[nd] and 3[rd] generation ALKi impacted significantly on median OS: Crizotinib alone (n=8) 17 months, Crizotinib followed by Ceritinib and/or Brigatinib/Alectinib (n=12) median OS not reached and 3 months for other therapies (n=6) (p<0.000).
Conclusion:
Small differences in OS were observed, depending on the treatment centers, but the use of multiple EGFR and ALK-I impacted highly significantly on the outcome of patients with EGFR and ALK-alterations in a real life setting.
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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 | Author(s): Frank Griesinger
- 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.
