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D. Cortinovis
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-063 - Molecular Profiling in Advanced Non-Small-Cell Lung Cancer: Preliminary Data of an Italian Observational Prospective Study (ID 4529)
14:30 - 15:45 | Author(s): D. Cortinovis
- Abstract
Background:
Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to patients’ histological and clinical features. Despite the existence of national guidelines, routine care is still heterogeneous. Aim of this observational study was to obtain prospectively a clinical practice picture of molecular testing and therapeutic choices in advanced NSCLC patients.
Methods:
Newly diagnosed metastatic or recurrent NSCLC patients enrolled in 38 Italian centres, from November 2014 to November 2015, have been included in the study. Baseline information were collected about molecular profiling performed and therapies.
Results:
A total of 1787 patients were enrolled (64% males, 36% females; median age 67 years-old; 22% never smokers, 31% current smokers, 47% former smokers; 75% adenocarcinoma, and 73% with PS ECOG 0 or 1). The 73.9% of diagnosis was histological, while 26.1% was cytological. 1382 (77%) patients were tested for one or more molecular analysis during the history of disease, for a total of 3532 molecular tests. Only 405 patients did not receive any molecular test. 32.3% of patients presented a genetic alteration: EGFR mutation was reported in 17.8% of cases (319/1787), ALK translocation in 8.8% (82/926), KRAS mutation in 31.9% (154/482), MET amplifications in 15.8% (10/63), BRAF mutations in 3.7% (9/241), ROS1 translocation in 4% (11/269), HER2 mutation in 3.3% (3/89) of cases and FGFR alteration was found in 3 cases (only 15 tested). Considering patients younger than 45 years, never smokers and females, an EGFR mutation was detected in 25.4%, 43.5% and 30.6%, respectively. While 15.6%, 9.5% and 6.3% were ALK rearranged, respectively. For patients receiving an EGFR tyrosine-kinase inhibitor as first-line treatment, among those whose data are evaluable (79.2%), the median interval from diagnosis to first-line was 35 days. EGFR mutated patients received first-line erlotinib, gefitinib and afatinib in 9.4%, 39.1% and 33.8% of cases, respectively. At time of analysis, ALK-rearranged patients received an ALK inhibitor (crizotinib, alectinib or ceritinib) as first and/or second-line in 71.9% of cases. 29.3% of all patients received a maintenance therapy, mainly with pemetrexed (91.2% of cases).
Conclusion:
Routine molecular assessing is properly performed according to the national guidelines. A selection bias in including only those patients performing molecular tests, may explain the high proportion of patients with a molecular alteration. The low number of patients tested for ALK could be partially related to the impossibility to prescribe Crizotinib in first- line. In more than 70% of cases EGFR mutated patients received gefitinib or afatinib as first-line treatment.
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P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02a-025 - PROs With Ceritinib Versus Chemotherapy in Patients With Previously Untreated ALK-rearranged Nonsquamous NSCLC (ASCEND-4) (ID 5128)
14:30 - 15:45 | Author(s): D. Cortinovis
- Abstract
Background:
Here, we present the patient-reported outcomes (PROs) of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.
Methods:
Untreated, ALK+, advanced, nonsquamous NSCLC patients (N=376) were randomized (1:1) to ceritinib 750 mg/day (n=189) or chemotherapy (n=187; [pemetrexed 500 mg/m[2 ]plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed). PROs were assessed using EORTC quality-of-life questionnaire (QLQ-C30), the lung cancer module (QLQ-LC13), Lung Cancer Symptom Scale (LCSS), and EQ-5D.
Results:
Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. PRO compliance was high, ≥80% at most timepoints. Ceritinib significantly prolonged time to deterioration of lung cancer-specific symptoms (pain, dyspnea, and cough) versus chemotherapy in both LCSS and QLQ-LC13 instruments (composite endpoints for LCSS, HR=0.61 [0.41, 0.90]; and QLQ-LC13, HR=0.48 [0.34, 0.69]). Time to deterioration in LC13 questionnaire was significantly longer with ceritinib versus chemotherapy (23.6 [20.7, NE] vs 12.6 [8.9, 14.9] months) (Table). In the QLQ-C30 instrument, 4 of 5 functional domains and 6 of 9 symptom scales improved with ceritinib (P< 0.05); 2 scales related to gastrointestinal symptoms indicated deterioration for ceritinib. In agreement with most other scales showing symptom improvement, ceritinib demonstrated significant improvements in Global Health Status/QoL in the same instrument (QLQ-C30, P<0.001) as well as for EQ-5D-5L index (P<0.001) and EQ-5D-5L VAS (P<0.05 from cycle 13 until 49). Figure 1
Conclusion:
Untreated ALK+ NSCLC patients experienced significantly greater improvements in lung cancer-specific symptoms on treatment with ceritinib. General health status was significantly improved with ceritinib versus chemotherapy. Overall, PRO results from all 4 instruments independently showed improvements highlighting the consistency and robustness of these findings.
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PL03 - Presidential Symposium (ID 428)
- Event: WCLC 2016
- Type: Plenary
- Track:
- Presentations: 1
- Moderators:D.P. Carbone, R. Pirker
- Coordinates: 12/06/2016, 08:35 - 10:25, Hall D (Plenary Hall)
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PL03.07 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4) (Abstract under Embargo until December 6, 7:00 CET) (ID 4987)
08:35 - 10:25 | Author(s): D. Cortinovis
- Abstract
- Presentation
Background:
Here, we report results of ceritinib versus chemotherapy as first-line treatment for advanced ALK+ NSCLC.
Methods:
Untreated ALK+ (IHC confirmed), advanced, nonsquamous NSCLC patients (N=376; median age, 54 years) were randomized (1:1) to ceritinib 750 mg/day (n=189 [59 with brain metastases (BM)]) or chemotherapy (n=187 [62 with BM]; [pemetrexed 500 mg/m[2] plus cisplatin 75 mg/m[2] or carboplatin AUC 5-6] for 4 cycles followed by maintenance pemetrexed), stratified by WHO PS (0 vs 1-2), BM at screening, and prior neo-/adjuvant chemotherapy. Crossover from chemotherapy to ceritinib was allowed at progression (n=80 crossed-over).
Results:
Median treatment exposure was 66.4 weeks for ceritinib and 26.9 weeks for chemotherapy. Median follow-up duration was 19.7 months (randomization to cut-off date). The study met its primary objective, with ceritinib demonstrating statistically significant improvement in BIRC PFS (RECIST 1.1; median, 16.6 [12.6, 27.2] vs 8.1 months [5.8, 11.1], HR=0.55, P<0.001) versus chemotherapy. OS was immature (HR, 0.73 [0.50, 1.08]; P=0.056) with 42.3% of required events at interim analysis. ORR (BIRC, 72.5% vs 26.7%) and DOR (BIRC, median, 23.9 vs 11.1 months) were also higher with ceritinib versus chemotherapy. Among patients with measurable baseline BM and ≥1 postbaseline assessment, intracranial ORR (BIRC neuroradiologist; modified RECIST v1.1) was higher with ceritinib (72.7% [49.8, 89.3] vs 27.3% [10.7, 50.2]) versus chemotherapy (Table). Most common AEs (>50%) with ceritinib were diarrhea (84.7%), nausea (68.8%), vomiting (66.1%), ALT increase (60.3%), and AST increase (52.9%). Overall, 5.3% ceritinib- and 11.4% chemotherapy-treated patients discontinued due to AEs suspected to be drug-related. Figure 1
Conclusion:
First-line ceritinib achieved statistically significant and clinically meaningful improvement in median PFS with an estimated 45% risk reduction in advanced ALK+ NSCLC versus chemotherapy including maintenance. Moreover, ceritinib achieved high and durable systemic responses and high OIRR in patients with measurable BM. Safety profile of ceritinib is consistent with previously reported.
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