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G. De Castro Jr
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-030 - Consolidation Chemotherapy Following Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer: A Brazilian Multicentric Cohort (ID 4670)
14:30 - 14:30 | Author(s): G. De Castro Jr
- Abstract
Background:
Locally advanced stage III grossly accounts for 25% newly diagnosed non-small cell lng cancer (NSCLC) cases. Albeit some patients (pts) are amenable to surgical resection, most will be treated with concurrent chemoradiation (CRT), whilst the addition of consolidation chemotherapy (CC) is still a debatable topic. We decided to look into the impact of CC in stage III NSCLC Brazilian pts treated in the daily clinical practice.
Methods:
We retrospectively collected data of stage III NSCLC pts treated in five different Brazilian cancer institutions from Jan/2007 to Dec/2011, whom have received CRT followed or not by CC. Eligible pts were ≥18yo and must have been treated with cisplatin or carboplatin plus etoposide, paclitaxel or vinorelbine, concurrently with thoracic irradiation (RT). Patients treated with surgery or neoadjuvant chemotherapy were excluded. Primary endpoint was overall survival (OS) from the date of diagnosis. Association between CC and clinical variables and demographics were evaluated by Pearson´s Chi-square test (Χ²). Survival curves were calculated by Kaplan-Meier method and compared by log-rank test. Univariate and multivariate analysis were made using Cox proportional model (CPM). P-values<0.05 were deemed statistically significant.
Results:
We collected data from 165 pts. Median age was 60yo (range: 27-79) and most pts were male (69.1%), Caucasian (77.9%), current or former smoker (93.3%), and staged as IIIB (52.7%). Adenocarcinoma was the most common histologic type (47.9%). Weight loss>5% and ECOG-PS 2 were observed in 39.1% (n=61) and 14.6% (n=24), respectively. Median follow-up was 25 mo. CC was administered to 27 pts. The only variable associated with CC was T stage (Χ²(4) = 11.410, p=0.022), with more T3 tumors receiving CC than expected. We observed no statistically significant difference in OS between patients treated or not with CC (p=0.211), although 3-year OS rate was numerically higher in CC pts (40% vs. 31%). Median OS in was 24 and 25 months in CC and no CC groups, respectively (HR 1.408, 95%CI 0.814-2.434). A total delivered RT dose ≥ 61Gy was the only variable independently associated with improved survival (HR 0.617, 95%CI 0.419-0.909, p=0.012).
Conclusion:
CC did not improve OS in stage III NSCLC patients after concurrent CRT. RT dose < 61 Gy negatively impacted OS.
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P2.06 - Poster Session with Presenters Present (ID 467)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Scientific Co-Operation/Research Groups (Clinical Trials in Progress should be submitted in this category)
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.06-022 - First-Line Durvalumab plus Tremelimumab vs Platinum-Based Chemotherapy for Advanced/Metastatic NSCLC: Phase 3 NEPTUNE Study (ID 4610)
14:30 - 14:30 | Author(s): G. De Castro Jr
- Abstract
Background:
Current first-line therapy for advanced EGFR and ALK wild-type NSCLC is associated with poor survival and there remains a significant need for more effective treatments in this population. Blockade of immune checkpoints programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) represents a promising anticancer therapeutic strategy. In preclinical models, targeting both PD-1 and CTLA-4 provides for non-redundant pathway blockade and potential synergy. Durvalumab (MEDI4736) is a selective, high-affinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) binding to PD-1 (IC~50~ 0.1 nM) and CD80 (IC~50~ 0.04 nM). Tremelimumab is a selective human IgG2 mAb inhibitor of CTLA-4. A Phase 1b study of durvalumab + tremelimumab demonstrated encouraging clinical activity and a manageable tolerability profile in advanced NSCLC, with activity observed in patients with high and low/no tumour PD-L1 expression (NCT02000947).
Methods:
NEPTUNE (NCT02542293) is a randomised, open-label, multicentre, global, Phase 3 study. Immunotherapy- and chemotherapy-naïve patients with advanced/metastatic EGFR and ALK wild-type NSCLC (with either PD-L1 high expression [≥25% tumour cells staining for PD-L1 at any intensity] or PD-L1 low/negative expression [<25% tumour cells staining for PD-L1 at any intensity] ) will be randomised (1:1) to durvalumab (20 mg/kg i.v. every 4 weeks [q4w] for up to 12 months) + tremelimumab (1 mg/kg i.v. q4w for up to 4 doses); or standard-of-care platinum-based doublet chemotherapy. The primary endpoint is overall survival (OS). Secondary endpoints are progression-free survival (PFS), objective response rate (ORR), duration of response and proportion of patients alive and progression free at 12 months by investigator assessment (RECIST v1.1); time from randomisation to second progression; OS, PFS and ORR in patients with PD-L1 low/negative NSCLC; safety (CTCAE v4.03) and tolerability; pharmacokinetics; and immunogenicity. Exploratory outcomes include potential biomarkers of response to treatment and impact of subsequent anticancer therapies on OS. Recruitment is ongoing. Figure 1
Results:
Not-applicable
Conclusion:
Not-applicable
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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 - 14:30 | Author(s): G. De Castro Jr
- 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)
09:45 - 09:55 | Author(s): G. De Castro Jr
- 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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PR03 - Press Conference: Accurate Diagnosis (ID 477)
- Event: WCLC 2016
- Type: Press Conference
- Track:
- Presentations: 1
- Moderators:T. Mok
- Coordinates: 12/06/2016, 10:30 - 11:45, Schubert 1
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PR03.04 - First-line Ceritinib Versus Chemotherapy in Patients With ALK-rearranged (ALK+) NSCLC: A Randomized, Phase 3 Study (ASCEND-4) (ID 7212)
10:30 - 10:30 | Author(s): G. De Castro Jr
- Abstract
- Presentation
Abstract not provided
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