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A.B. Cortot
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MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:M. Sebastian, E.B. Garon
- Coordinates: 12/06/2016, 14:20 - 15:50, Strauss 2
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MA09.11 - Efficacy and Safety of Necitumumab and Pembrolizumab Combination Therapy in Stage IV Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (ID 4712)
14:20 - 15:50 | Author(s): A.B. Cortot
- Abstract
- Presentation
Background:
Trials of anti-EGFR necitumumab and anti-PD1 pembrolizumab demonstrate the anti-tumor activity of each agent in NSCLC.
Methods:
Single-arm, multicenter Phase 1b study to investigate effectiveness and safety of necitumumab combined with pembrolizumab in patients with Stage IV NSCLC (NCT02451930). In Part A, escalating doses of necitumumab (600 mg and 800 mg IV) were administered on Day 1 and 8 every 3 weeks (Q3W) in combination with pembrolizumab (200 mg IV) on Day 1 Q3W. In the absence of dose limiting toxicity, Part B (expansion cohort) was planned with necitumumab 800 mg in 27 squamous and 27 nonsquamous NSCLC patients. Major eligibility criteria included: progression after ≥1 platinum-based chemotherapy, and ECOG PS 0-1. Study objectives were to evaluate tolerability and ORR by RECIST 1.1. PD-L1 status was centrally assessed using PD-L1 IHC 22C3 pharmDx assay (considered negative, weak positive, strong positive if <1%, 1-49%, ≥50% of tumor cells were stained, respectively).
Results:
The interim analysis population includes 34 nonsquamous patients (median age 61 years, 68% men, 21% never smokers, PD-L1 status: negative, 50% [17/34]; positive weak/strong, 15% [5/34]/15% [5/34]; unknown 21% [7/34[BJ1] ]). Median follow-up was 6.0 months. Ten patients (29.4%) had PR (confirmed and unconfirmed) (PRs by PD-L1 status: negative, 18% [3/17]; positive weak/strong, 60% [3/5]/40% [2/5]; unknown status, 2 patients). DCR was 67.6%. PFS rate at 6 months was 55.1% (95% CI, 36.2-70.6); median PFS was 6.9 months (95% CI, 2.7-NR). Most common Grade ≥3 AEs were skin rash (9%), hypomagnesemia (9%), VTE (9%) and increased lipase (9%); 1 patient died due to an AE (respiratory tract infection). Five patients (14.7%) discontinued therapy because of an AE. Figure 1
Conclusion:
Safety profile corresponds to individual profiles for both drugs, with no additive toxicities. These preliminary data suggest activity of this combination in a pretreated nonsquamous NSCLC population, irrespective of PD-L1 status.
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MA10 - Facing the Real World: New Staging System and Response Evaluation in Immunotherapy (ID 393)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:P. Kosmidis
- Coordinates: 12/06/2016, 14:20 - 15:50, Stolz 2
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MA10.10 - [18F]-FDG-PET/CT Early Response to Nivolumab in NSCLC (ID 6211)
14:20 - 15:50 | Author(s): A.B. Cortot
- Abstract
- Presentation
Background:
Nivolumab is approved for treatment of squamous and non-squamous advanced NSCLC. Since nivolumab restores antitumor immunity, it is not clear whether 18F-FDG-PET/CT is able to distinguish response from tumor progression. We evaluated early metabolic patterns of response to nivolumab in advanced NSCLC patients.
Methods:
We retrospectively reviewed PET/CT scans and paired CT scans from 22 patients with advanced NSCLC who received nivolumab 3mg/kg every 2 weeks and performed PET/CT before and after 4 infusions of nivulomab. Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV) of every lesion up to 5 per patient were measured on baseline and follow-up PET/CT. Percentage changes in MTV (ΔMTV) and TLG (ΔTLG) between the two PET/CT were calculated. Patients were classified into responders (nivolumab for >6 months), non responders (nivolumab ≤6 months) or having pseudo-progression (PP, nivolumab and clinical benefit >6 months despite initial progressive disease according to RECIST criteria)
Results:
Among 22 patients, 6 (27%) were responders, 15 (68%) were non-responders and 1 (4.5%) had PP. Baseline MTV and TLG were significantly lower in responders than in non-responders (medians 27 vs. 63 mL, p=0.03 and 124 vs. 254 g, p=0.04, respectively). After 4 infusions of nivolumab, metabolic parameters were significantly lower in responders than in non-responders (median MTV : 2 vs. 148 mL, p=0.001 and median TLG : 6 vs. 835 g, p=0.002). Mean ΔMTV and ΔTLG were both -88% in responders, and +236% and +312% respectively in non-responders, which was significantly different (p=0.0005). The only patient with PP had lower ΔMTV (+11%) and ΔTLG (+41%) than non-responders patients.
Conclusion:
In NSCLC, objective response and disease progression upon nivolumab usually translate into early and clear-cut patterns of change in PET/CT. Early PET/CT may help to distinguish progression from pseudo-progression.
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OA11 - Angiogenesis in Advanced Lung Cancer (ID 387)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:L.M. Montuenga, J. Heymach
- Coordinates: 12/06/2016, 11:00 - 12:30, Stolz 2
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OA11.01 - Prolonged OS of Patients Exposed to Weekly Paclitaxel and Bevacizumab: Impact of the Cross-Over in the IFCT-1103 ULTIMATE Study (ID 4988)
11:00 - 12:30 | Author(s): A.B. Cortot
- Abstract
- Presentation
Background:
Overall survival (OS) is considered as the gold standard for evaluating efficacy of antineoplastic treatments, including chemotherapy and targeted therapies. In randomized trials, allowing patients to cross-over to the other arm usually prevents demonstration of a survival benefit. However, it may provide important information with clinical relevance.
Methods:
The phase III IFCT-1503 ULTIMATE study compared weekly paclitaxel and bevacizumab (wPB) vs. docetaxel (DOC) as second- or third-line therapy in non-squamous NSCLC. At progression, patients were allowed to cross over to the other arm. Date of progression was collected for patients who crossed over to the other arm and for those who did not cross over but received a post-discontinuation treatment within 60 days following progression. Post-discontinuation progression-free survival (PFS2) and OS2 were calculated from day 1 of post-discontinuation treatment.
Results:
The study met its primary endpoint, PFS, which was significantly improved in the wPB arm (medians 5.4 vs. 3.9 mo, hazard ratio (HR) 0.62, p=0.006). No overall survival was observed (medians 9.9 vs. 11.4 mo, HR 1.18, p=0.4). Out of patients treated with DOC (n=55), those who crossed over to wPB (n=21, 38.2%) had a median PFS2 of 4.9 mo [3.1-6.2] and a median OS2 of 12.5 mo (7.0-NR), whereas those who did not cross over but received a post-discontinuation treatment (n=13, 23.7%) had a median PFS2 of 1.7 mo [1.1-2.2] and a median OS2 of 4.1 mo [2.1-5.9]. Out of patients treated with wPB (n=111), median PFS2 was 1.9 mo [1.2-2.2] for those who crossed over to DOC (n=9, 8.3%) and median PFS2 and OS2 were 1.9 mo [1.7-2.6] and 5.0 m [3.4-9.0] for those who did not cross over but received a post-discontinuation treatment (n=57, 52.3%).
Conclusion:
Allowing patients to cross over to the other arm demonstrated benefit of wPB following progression on docetaxel and explains the absence of OS benefit.
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P1.01 - Poster Session with Presenters Present (ID 453)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Epidemiology/Tobacco Control and Cessation/Prevention
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.01-010 - Awareness of Lung Cancer Risk Factors among Lay Persons and Physicians (ID 4686)
14:30 - 15:45 | Author(s): A.B. Cortot
- Abstract
Background:
Tobacco consumption, and more specifically active smoking, remains the main risk factor for lung cancer (LC) and continues to be the target of awareness campaigns worldwide. However, in recent decades, other risk factors have been identified, including passive smoking, atmospheric pollution and occupational exposure. This analysis focuses on awareness of LC risk factors among the lay population and physicians.
Methods:
The 4th French nationwide observational survey, EDIFICE 4, was conducted by phone interviews of a representative sample of 1602 subjects, aged between 40 and 75 years, from June 12 to July 10, 2014. A mirror survey was also conducted by phone among physicians between July 9 and August 8, 2014. Both surveys were conducted using the quota method on representative samples of 1602 lay persons and 301 physicians. The following analyzes were conducted amongst 1463 lays persons with no history of cancer and 301 physicians. Interviewees were asked to cite the five main risk factors for LC.
Results:
LC risk factors associated with tobacco in general were widely cited in first position by both physicians and the lay population (100% and 96%, respectively; P≤0.01), with the role of active smoking (100% vs 94%, P≤0.01) and passive smoking (77% vs. 68%, P≤0.01) clearly identified. Twice as many physicians cited asbestos as a risk factor, ranking it in second place, compared with the lay population (77% vs. 30%, P≤0.01). Atmospheric pollution was cited to the same degree by physicians and the lay population (49% vs. 43%, P=0.05), the latter ranking it second. Heredity and family history came fourth (32% vs. 13%, P≤0.01) and alcohol fifth (13% vs. 10%, not statistically significant), in both populations. Infections and other respiratory disorders were cited by less than one person in ten (7%). Poor dietary habits were very rarely cited by either physicians or the lay population (<1% vs 4%, respectively, P≤0.01).
Conclusion:
The awareness of risk factors for lung cancer is broadly consistent with the established risk factors, among both physicians and the lay persons in our survey. As expected, tobacco was ranked first, followed by atmospheric pollution and asbestos, though the latter is less present in the mind of the lay population compared to physicians. It is noteworthy that even among physicians, a history of respiratory disorders was only marginally acknowledged.
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P1.03 - Poster Session with Presenters Present (ID 455)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Radiology/Staging/Screening
- Presentations: 2
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.03-018 - FDG-PET/CT in Patients with EGFR-Mutated NSCLC Treated with TKI. Can We Identify Early Lesions at Higher Risk of Progression? (ID 6159)
14:30 - 15:45 | Author(s): A.B. Cortot
- Abstract
Background:
EGFR TKIs in EGFR-mutated NSCLC patients yield heterogeneous progression-free survivals ranging from <3 months to >3 years. Early identification of lesions that are more likely to progress may provide rationale for aggressive treatment of these lesions. We questioned whether FDG-PET/CT could identify early lesions with higher risk of progression.
Methods:
Eighty-nine lesions from 13 caucasian EGFR-mutated NSCLC patients treated with TKI were analyzed. Date of progression for each lesion was collected. SUVmax, Metabolic Tumor Volume (MTV), Total Lesion Glycolysis (TLG) were measured on baseline and early follow-up PET/CT performed 2-3 months later. Variations between the 2 PET/CT (ΔSUVmax, ΔMTV, ΔTLG) were calculated. Medians were used as cut-off values for statistical analysis. Risk of progression was analyzed according to PET/CT parameters and Odds Ratios (OR) were calculated.
Results:
The best metabolic predictors of progression were high SUVmax (>0, i.e. incomplete visual response, OR =9.6, p<0.001), high MTV (>0, OR=8.3, p<0.001) and high TLG (>0, OR=9.6, p<0.001) on the early follow-up PET/CT. ΔSUVmax<97.6% (OR=3.9, p=0.02) was also associated with early progression, whereas ΔMTV (p=0.23) and ΔTLG (p=0.17) were not.
Conclusion:
Lesions with incomplete visual response on early follow-up FDG-PET/CT upon EGFR TKIs in EGFR-mutated NSCLC show significantly higher risk of progression. Aggressive treatment of these lesions with residual metabolic activity may be further evaluated.
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P1.03-040 - Beliefs Surrounding Lung Cancer Screening among Physicians and Lay Populations: Results from the EDIFICE Survey (ID 4436)
14:30 - 15:45 | Author(s): A.B. Cortot
- Abstract
Background:
The National Lung Cancer Screening Trial has shown that lung cancer screening (LCS) with an annual low-dose chest CT-scan reduces specific mortality in both former and current heavy smokers. However, organizational issues have yet to be solved before it can be systematically implemented. We investigated the perceptions of the population at large as well as those of physicians with regard to the efficacy of LCS, and target populations in terms of tobacco use.
Methods:
The 4th French nationwide observational survey, EDIFICE 4, was conducted by phone interviews of a representative sample of 1602 subjects, aged between 40 and 75 years, from June 12 to July 10, 2014. A mirror survey was also conducted by phone among physicians between July 9 and August 8, 2014. Both surveys were conducted using the quota method on representative samples of 1463 lay persons and 301 physicians with no history of cancer.
Results:
For 53% of lay persons and 33% of physicians interviewed (P<0.01), generalization of LCS is potentially an effective way to reduce lung cancer mortality. For the majority of interviewees (58% of lay persons and 55% of physicians; difference not statistically significant [NS]), offering LCS to the whole population would not encourage smokers to continue smoking. The table shows lay persons’ and physicians’ replies concerning possible target populations within the whole population and among smokers. Figure 1
Conclusion:
Lay persons are more inclined to suggest generalizing LCS to the whole population, independently of current smoking status or quitting issues. Lay persons and physicians alike agree with generalizing LCS to all smokers, regardless of their tobacco consumption.
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-040 - Home-Based Pulmonary Rehabilitation in Advanced Non Small Cell Lung Cancer Patients Treated by Oral Targeted Therapy: A Feasibility Study (ID 4453)
14:30 - 15:45 | Author(s): A.B. Cortot
- Abstract
Background:
Pulmonary rehabilitation (PR) is valuable in the peri-operative setting of non small cell lung cancer (NSCLC) patients, but not established for stage IIIB-IV disease. Previously, we showed that home-based PR is feasible and may significantly improve quality of life (QoL) and functional status of NSCLC patients treated by chemotherapy (submitted). The goal of this study was to assess the feasibility and value of home-based PR in advanced NSCLC patients treated by oral targeted therapies.
Methods:
Advanced NSCLC patients with oral targeted therapy were recruited in a prospective study in 2015-2016 in Lille University Hospital, France. After written informed consent, they benefited from 8 weeks home-based PR including functional exercises, psychological and nutrition support, therapeutic education. Exclusion criteria were cardiovascular contraindication to PR, symptomatic brain metastasis, bone metastasis with high fracture risk, or severe cognitive disorder. Main endpoints were adherence, inclusion rate, and cause of refusal. Secondary endpoints were PR benefits assessed by QoL scales (EORTC QLQ C 30, FACT-L, HAD); functional capacity: 6min walk test, 6 min stepper test, spirometry, respiratory muscle strength; and global condition: nutrition, treatment tolerance. This study was approved by local Ethical Committee
Results:
Among 36 screened patients, the adhesion rate was 55.6% with 20 patients joining the study. Other patients refused mostly because (a) of “lack of interest for PR and they don’t want to be disturbed” (40% of cases), or (b) they considered “their physical activity already sufficient” (12%), or (c) “family constraints” (12%). Only 15 patients (41.6%) started PR (3 early deaths, 1 exclusion for intraventricular thrombosis, 1 consent withdrawal). No serious adverse event was reported but only grade 1 asthenia or musculoskeletal pain. Significant increases of FACT-L score from 84.7 to 100.2 (p=0.02) and 6 min stepper test from 140 to 195.7 steps (p=0.01) were found after PR, and preservation of patients’ autonomy reflected by stability of 6WT data. Most of other parameters exhibited a positive but not significant trend, likely due to the limited number of participants.
Conclusion:
Home-based PR is feasible and well-tolerated in patients with advanced NSCLC treated by oral targeted therapies. Significant improvements were obtained with PR based on 6ST and QoL FACT-L data. Moreover, PR was highly appreciated by patients, their relatives, and all medical teams raising our will to be able to propose PR to all our stage III-IV NSCLC patients. Currently, this study is still ongoing and multicentric, aiming at recruiting 50 extra patients.
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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): A.B. Cortot
- 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): A.B. Cortot
- 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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