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A. Dingemans
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MA06 - Locally Advanced NSCLC: Risk Groups, Biological Factors and Treatment Choices (ID 379)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:P. Van Houtte, M. Zemanová
- Coordinates: 12/05/2016, 16:00 - 17:30, Strauss 2
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MA06.05 - Screening for Brain Metastases in Patients with Stage III NSCLC, MRI or CT? A Prospective Study (ID 5664)
16:30 - 16:36 | Author(s): A. Dingemans
- Abstract
- Presentation
Background:
In all current non-small cell lung cancer (NSCLC) guidelines it is advised to screen all stage III patients for brain metastases, preferably by magnetic resonance imaging (MRI), or otherwise a contrast-enhanced computed tomography (CE-CT). Access to MRI can be problematic and a dedicated brain CE-CT can be incorporated in the staging [18]Fluodeoxoglucose-positron-emission-tomography ([18]FDG-PET)-CT scan. The additive value of a brain MRI after a dedicated brain CE-CT scan is unknown.
Methods:
In this observational prospective multicentre study all consecutive stage III NSCLC patients scheduled for treatment with curative intent from three Dutch hospitals who underwent a dedicated brain CE-CT incorporated in the staging [18]FDG-PET and an additional brain MRI were included. Patients with another primary tumour within 2 years of NSCLC diagnosis were excluded. Data regarding patient characteristics and imaging results were collected. Primary endpoint was the percentage of patients diagnosed with brain metastases on MRI without suspect lesions on CE-CT. 118 patients were needed to show a clinically relevant considered difference of 2%.
Results:
Between December 14[th] 2012 and July 15[th] 2016, 264 consecutive patients had an extracranial stage III NSCLC based on [18]FDG-PET. 111 out of these 264 patients (42.0%) were excluded because of no dedicated brain CE-CT 57 (51.4%) had only a low dose CT for attenuation correction, 54 (48.6%) had a CE-CT but without dedicated brain imaging protocol). Fourty (26.1%) of the remaining 153 patients were excluded because of asymptomatic brain metastases on dedicated CE-CT brain (N=8), second primary (N=6) or no brain MRI (N=26). 113 stage III patients were included (updated results of 118 patients will be presented). 57.5% of the included patients were male; mean age was 67.0 years, 84.1% had WHO PS 0-1, 60.2% had stage IIIA (before MRI brain) and 42.5% had an adenocarcinoma. Median time (range) between [18]FDG-PET-CE-CT and MRI was 2.0 (0.0 -8.1) weeks. 5/113 (4.4%) patients had a solitary brain metastasis on MRI despite no suspect brain lesions on CE-CT. In retrospect, in one of these five patients a solitary brain metastasis could be identified on the [18]FDG-PET–CE-CT.
Conclusion:
Although asymptomatic brain metastasis were detected in staging CE-CT, MRI brain is in daily practice clinically relevant superior to a CE-CT in screening for brain metastases in stage III NSCLC
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-025 - Evaluation of NGS and RT-PCR Methods for ALK Assessment in European NSCLC Patients: Results from the ETOP Lungscape Project (ID 5001)
14:30 - 14:30 | Author(s): A. Dingemans
- Abstract
Background:
The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%, depending on population and detection method. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been advocated and most recently the advent of targeted Next-Generation Sequencing (NGS) for ALK and other fusions has become possible. This is one of the first studies comparing all 4 techniques in resected NSCLC from the large ETOP Lungscape cohort.
Methods:
96 cases from the ETOP Lungscape iBiobank (N=2709) selected based on any degree of IHC staining (clone 5A4 antibody, Novocastra, UK) were examined by FISH (Abbott Molecular, Inc.; Blackhall, JCO 2014), central RT-PCR and NGS. H-score 120 is used as cutoff for IHC+. For both RT-PCR and NGS, RNA was extracted from the same formalin-fixed, paraffin-embedded tissues. For RT-PCR, primers were used covering the most frequent ALK translocations. For NGS, the Oncomine™ Solid Tumour Fusion Transcript Kit was used, allowing simultaneous sequencing of 70 ALK, RET and ROS1 specific fusion transcripts associated with NSCLC, as well as novel ALK translocations using 5’-3’ ALK gene expression ‘Imbalance Assay’.
Results:
NGS provided results for 90 cases, while RT-PCR for 77. Overall, 70 cases have results for all 4 methods, with fully concordant 60 (85.7%) cases (49 ALK-, 11 ALK+). Before employing the ‘Imbalance Assay', in 5 of the remaining 10 cases, NGS differs from the other methods (3 NGS-, 2 NGS+), while in the other 5, NGS agrees with RT-PCR in all, IHC in 2, and FISH in 1. Using the concordant result of at least two of the three methods as true negative/positive, the specificity and sensitivity of the fourth is 96/94/100/96% and 94/94/89/72% for IHC/FISH/RT-PCR/NGS, respectively (incorporating imbalance: NGS sensitivity=83%). Imbalance scores are presented here for 18 NGS- cases: 9 ‘NGS-/FISH+/IHC+’, 9 ‘NGS-/FISH-/IHC-‘. Among the ‘NGS-/FISH+/IHC+’, there is strong evidence of imbalance in 4 cases (score’s range: 0.0144-0.0555), uncertain in 5 (range: 0.0030-0.0087), and no evidence (scores≤0.0004) in the 9 negative cases.
Conclusion:
NGS is a useful screening tool for ALK rearrangement status, superior to RT-PCR when RNA yield is limited. When using NGS, it is critically important to integrate the 5’-3’ imbalance assay and to confirm with one or more additional methods in the ‘imbalance’ cases. Data further highlight the possibility of missing actionable rearrangements when only one screening methodology is available.
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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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P2.02-021 - Extracranial Progression (ePD) after Chemoradiotherapy (CRT) for Stage III NSCLC: Does the Chemotherapy Regimen Matter? (ID 4887)
14:30 - 14:30 | Author(s): A. Dingemans
- Abstract
Background:
In stage III NSCLC concurrent chemoradiation (cCRT) compares favourably to sequential CRT (sCRT). No superior chemotherapy regimen has been identified regarding (extracranial)PD. Previously we reported that the specific chemotherapy did not influence symptomatic brain metastases incidence. Here we analyse whether the specific chemotherapy influences occurrence of extracranialPD as first PD site (ePD~first~) after CRT.
Methods:
This retrospective multicenter study included all consecutive stage III NSCLC patients that completed CRT between 01-2006 and 06-2014. Primary endpoint was ePD~first ~(with/without cranial PD). Differences between regimens were assessed using logistic regression modelling including known relapse risk factors (age, gender, stage, histology) and the specific chemotherapy: cCRT versus sCRT. Within cCRT: daily low dose cisplatin (LDC) versus cyclic dose polychemotherapy (CDC); LDC versus (non-)taxane CDC; LDC versus subgroups of ≥50 CDC patients).
Results:
838 patients (737 cCRT, 101 sCRT) from 5 institutions were eligible. Median follow-up [95% CI] was 45.1 [42.3-47.8] months. 530 (63.2%) had PD, of which 463 (87.4%) had ePD~first. ~Median time to ePD~first~ was 16.6 [14.5-18.7] months. Patients with ePD~first~ had more often squamous histology (p=0.04). ePD~first~% or median time to ePD~first~ was not different for sCRT versus cCRT (table 1). 461 (62.6%) patients had PD after cCRT, of whom 401 (87.0%) had ePD~first~. ePD~first~% or median time to ePD~first~ did not differ between LDC and CDC. The chemotherapy regimen (cCRT versus sCRT) did not influence ePD~first~ on multivariate analysis: OR 0.81 [0.52-1.24] (p=0.33). LDC versus CDC cCRT did not differ: OR 0.96 [0.72-1.29] (p=0.80). Comparable results were found for LDC versus CDC non-taxane (N=277) and CDC taxane regimens (N=69) and for cCRT regimens with ≥50 patients (LDC versus cisplatin/etoposide (N=188), cisplatin/vinorelbin (N=65), weekly cisplatin/docetaxel (N=60)).Table1
concurrent N=737 sequential N=101 p-value PD N(%) 461 (62.6) 68 (68.3) 0.18 ePDfirst N(%) -patients with concomitant brain metastases 401 (87.0) -38 (9.5) 62 (89.9) -8 (12.9) 0.19 median time to ePD [95%CI] months 17.5 [15.0-20.0] 14.3 [11.9-16.7] 0.16 LDC N=391 cyclic dose N=346 p-value PD N(%) 245 (62.7) 216 (62.4) 0.33 ePDfirst N(%) -patients with concomitant brain metastases 211 (86.1) -17 (8.1) 190 (88.0) -21 (11.1) 0.80 median time to ePD [95%CI] months 17.4 [14.3-20.5] 18.3 [14.2-22.5] 0.59
Conclusion:
Sixty-three percent of stage III NSCLC patients developed PD, of whom 87% had ePD~first~. Incidence of ePD~first~ is independent of the specific chemotherapy regimen.
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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-016 - Pooled Efficacy and Safety Data from Two Phase II Studies (NP28673 and NP28761) of Alectinib in ALK+ Non-Small-Cell Lung Cancer (NSCLC) (ID 5044)
14:30 - 14:30 | Author(s): A. Dingemans
- Abstract
Background:
Alectinib is an FDA-approved ALK TKI, for treatment of patients with ALK+ metastatic NSCLC who have progressed on, or are intolerant to, crizotinib. Systemic and CNS efficacy was demonstrated in two single-arm, phase II studies (NP28673 [NCT01801111] and NP28761 [NCT01871805]). We report the pooled systemic efficacy and safety analysis of alectinib from 2016 cut-offs 22 January, NP28761 and 1 February, NP28673.
Methods:
Patients were ≥18 years, had locally advanced or metastatic ALK+ NSCLC [FDA-approved FISH test] and had progressed on, or were intolerant to, crizotinib. Patients received oral alectinib 600mg twice daily until disease progression, death or withdrawal. The pooled analysis assessed objective response rate (ORR) by an independent review committee (IRC) using RECIST v1.1 (primary endpoint in both studies); disease control rate (DCR); duration of response (DOR); progression-free survival (PFS); overall survival (OS); and safety.
Results:
The pooled dataset included 225 patients, (n=138 NP28673; n=87 NP28761). Median age was 53 years, 60% of patients had baseline CNS metastases and 77% had received prior chemotherapy. The response-evaluable (RE) population by IRC included 189 patients (84%). Median follow-up was 18.8 months (0.6–29.7). In the RE population (n=189) ORR by IRC was 51.3% (95% CI 44.0–58.6; all partial responses), a DCR of 78.8% (95% CI 72.3–84.4), with a median DOR of 14.9 months (95% CI 11.1–20.4) after 58% of events. In patients with prior chemotherapy (n=148), IRC ORR was 49.3% (95% CI 41.0–57.7); DCR: 79.1% (95% CI 71.6–85.3); median DOR: 14.9 months (95% CI 11.0–21.9) after 59% of events. In patients who were chemotherapy-naïve (n=41), IRC ORR was 58.5% (95% CI 42.1–73.7); DCR: 78.0% (95% CI 62.4–89.4); median DOR: 11.2 months (95% CI 8.0–NE) after 54% of events. In the total pooled population (n=225) median PFS by IRC was 8.3 months (95% CI 7.0–11.3) after 69% of events and median OS was 26.0 months (95% CI 21.4–NE) after 43% of events. Grade ≥3 adverse events (AEs) occurred in 40% of patients and the most common were dyspnoea (4%), elevated levels of blood creatine phosphokinase (4%) and alanine aminotransferase (3%). The mean dose intensity was 94.6%. Fourteen patients withdrew due to AEs; 20.9% had AEs leading to dose interruptions/modification.
Conclusion:
This pooled analysis confirmed alectinib has robust systemic efficacy with a durable response in this population and in patients with or without prior chemotherapy. Alectinib had an acceptable safety profile.
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SC14 - Immunotherapy of NSCLC (ID 338)
- Event: WCLC 2016
- Type: Science Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:N. Rizvi, C. Zielinski
- Coordinates: 12/06/2016, 11:00 - 12:30, Hall C2
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SC14.05 - Tobacco Use and Immunotherapy (ID 6657)
12:10 - 12:25 | Author(s): A. Dingemans
- Abstract
- Presentation
Abstract not provided
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