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M. Nishio
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MINI 31 - ALK (ID 158)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:S. Malik, I. Ou
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 1a-1f
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MINI31.13 - Symptoms and QOL with Ceritinib in ALK+ NSCLC Patients with/without Brain Metastases (ID 1655)
19:40 - 19:45 | Author(s): M. Nishio
- Abstract
Background:
In the pivotal ASCEND-1 study, ceritinib, an anaplastic lymphoma kinase inhibitor (ALKi), showed clinical activity in patients with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC), including in patients with brain metastases (BrM). Here, patient-reported outcomes (PROs) from the recently reported ASCEND-2 study (NCT01685060) are described for chemotherapy- and ALKi-pretreated patients with ALK+ NSCLC with and without baseline BrM
Methods:
In ASCEND-2, adult patients with ALK+ NSCLC previously treated with chemotherapy and an ALKi (crizotinib) received oral ceritinib 750 mg daily. PROs were assessed at baseline and Day 1 of treatment cycles 2, 3, and every two cycles thereafter (1 cycle=28 days), using the Lung Cancer Symptom Scale (LCSS) and EORTC quality of life and lung cancer surveys (QLQ-C30 and QLQ-LC13, respectively). Data were analyzed by presence/absence of baseline BrM. Data beyond cycle 9 are not reported due to small sample sizes.
Results:
All 140 patients enrolled (median age [range] 51 [29–80] years; 50.0% male), had received ≥2 antineoplastic regimens and 100 (71.4%) had BrM at baseline. At data cutoff (13 August 2014), median follow-up was 11.3 months. PRO questionnaire compliance was at least 91.2% up to cycle 9. In the overall patient population, investigator-assessed disease control rate (DCR) was 77.1% and median duration of response (DOR) 9.7 months. Investigator-assessed whole-body DCR [95% confidence interval (CI)] in patients with and without baseline BrM was 74.0% [64.3, 82.3] and 85.0% [70.2, 94.3], respectively, while DOR [95% CI] was 9.2 [5.5, 11.1] and 10.3 [7.4, 16.6] months, respectively. Analysis of PROs data demonstrated that treatment with ceritinib improved lung cancer symptoms in patients with and without baseline BrM (Figure). QLQ-LC13 outcomes were broadly consistent with those of LCSS. In general, mean global quality of life (QLQ-C30) was maintained on treatment for both patient subgroups, with mean change from baseline in QLQ-C30 global health status ranging from -3.06 to +7.25 in patients without baseline BrM and -2.83 to +3.55 in those with baseline BrM. Figure 1
Conclusion:
In patients with ALKi-pretreated ALK+ NSCLC who received prior chemotherapy and ceritinib, clinical efficacy was demonstrated and cancer symptoms were mostly improved, with health-related quality of life generally maintained regardless of presence or absence of baseline BrM.
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MINI31.14 - PROs with Ceritinib in ALKi-Naive ALK+ NSCLC Patients with and without Brain Metastases (ID 1528)
19:45 - 19:50 | Author(s): M. Nishio
- Abstract
Background:
In the pivotal ASCEND-1 study, ceritinib, an anaplastic lymphoma kinase inhibitor (ALKi), demonstrated sustained clinical activity in ALKi-naive patients with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC), including in patients with brain metastases (BrM). ASCEND-3 (NCT01685138) evaluated patient-reported outcomes (PROs) as well as clinical outcomes with ceritinib, in ALKi-naive ALK+ NSCLC patients with and without baseline BrM.
Methods:
Adult patients with ALK+ NSCLC previously treated with up to 3 lines of cytotoxic therapy received oral ceritinib 750 mg daily. PROs were assessed using Lung Cancer Symptom Scale (LCSS) and EORTC (QLQ-C30, QLQ-LC13) quality of life and lung cancer surveys at baseline and Day 1 of treatment cycles 2, 3, and every two cycles thereafter (1 cycle=28 days). Data were analyzed by presence/absence of baseline BrM. Data beyond cycle 9 are not reported due to small sample sizes.
Results:
Of 124 enrolled patients (median age [range] 56 [27–82] years; 40.3% male), 50 (40.3%) had BrM at baseline. At data cutoff (27 June 2014), median follow-up was 8.3 months. Up to cycle 9, PRO questionnaire compliance was at least 97.0%. In the overall patient population, investigator-assessed disease control rate (DCR) was 89.5% and median duration of response (DOR) 9.3 months. Investigator-assessed whole-body DCR [95% confidence interval (CI)] in patients with and without baseline BrM was 86.0% [73.3, 94.2] and 91.9% [83.2, 97.0], respectively, while DOR [95% CI] was 9.1 [7.5, Not Estimable] and 10.8 [9.3, 10.8] months, respectively. Mean change from baseline in patients’ total LCSS score ranged from -3.4 to -11.4 while receiving ceritinib, with 82.1% of patients experiencing symptom improvement; symptoms improved in patients with and without baseline BrM (Figure). QLQ-LC13 outcomes were broadly consistent with those of LCSS in the full patient population and in the subgroups of patients with and without baseline BrM. In general, mean global quality of life (QLQ-C30) was maintained on treatment for all patients. Patients reported diarrhea and nausea and vomiting symptoms were worse than baseline, however, nausea and vomiting symptoms did reduce over time. Figure 1
Conclusion:
In ALKi-naive patients with ALK+ NSCLC, treatment with ceritinib demonstrated clinical efficacy and improved cancer symptoms, with health-related quality of life generally maintained regardless of baseline BrM status. Improvements were greatest for the lung-related symptoms, cough and pain.
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ORAL 17 - EGFR Mutant Lung Cancer (ID 116)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:P. Meldgaard, E. Felip
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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ORAL17.03 - Biomarkers for Efficacy in JO25567 Study Evaluating Erlotinib plus Bevacizumab versus Erlotinib in Advanced NSCLC with EGFR Mutation (ID 306)
11:07 - 11:18 | Author(s): M. Nishio
- Abstract
- Presentation
Background:
Bevacizumab (B), an anti-vascular endothelial growth factor (VEGF) monoclonal antibody has been proven to provide additional efficacy benefit in combination with platinum-based chemotherapy for 1[st] line therapy of non-squamous non-small cell lung cancer (NSCLC). In JO25567 study, we observed that bevacizumab in combination with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, erlotinib (E) also provided additional 6.3 months median progression free survival (PFS) in advanced EGFR mutation-positive non-squamous NSCLC. To try to understand this additional effect of bevacizumab, we investigated the predictive biomarkers related to angiogenesis comprehensively in JO25567 study. Clnical trials registry number: JapicCTI-111390
Methods:
We evaluated the biomarkers in blood and tissue samples. All samples were collected before E+B or E treatment in JO25567 study. Angiogenesis related ligands and soluble receptors in serum were analyzed by multiplex, bead-based suspension array. Single nucleotide polymorphisms (SNPs) or variable number of tandem repeats (VNTR) of angiogenesis related genes were analyzed by direct sequencing or electrophoresis after PCR for blood sample. VEGF-A concentration in plasma were analyzed by Immunological Multi-Parametric Chip Technique (IMPACT) assay. Messenger RNA of genes related to angiogenesis in tumor tissue were quantitated by multiplex TOF-mass spectrometry (MassARRAY). Immunohistochemistry of neuropilin and exploratory proteomics analysis were planned for surgically resected tumor tissues. PFS were used as an efficacy variable of prediction. Multivariate Fractional Polynomial (MFP) and Subpopulation Treatment Effect Pattern Plot (STEPP) were used for biomarker screening.
Results:
One hundred fifty-two patients were treated with E+B or E in JO25567 study. We analyzed 26 ligands or soluble receptors in 134 serum samples. Follistatin and leptin were identified as potential biomarkers by MFP. The interaction p-value with adjustment of covariates for biomarker and efficacy was 0.0168 for follistatin and 0.0049 for leptin. STEPP suggested that high follistatin related to limited bevacizumab efficacy and low leptin related to higher bevacizumab efficacy. SNPs could be analyzed in 135 blood samples. In 12 SNPs and 1 VNTR of 8 genes, no gene related to bevacizumab efficacy. Plasma samples were collected from 105 patients. Median VEGF-A concentration of E+B group and E group were 18.0 pg/mL and 18.8 pg/mL respectively and was one sixth or more lower than previously reported breast and gastric cancers. Hazard ratio of E+B comparing with E for was 0.23 (95% CI: 0.09-0.60) for low plasma VEGF and was 0.56 (95% CI: 0.26-1.25) for high plasma VEGF. This trend was not consistent with previously reported studies. We analyzed mRNA expression from 24 surgical resected tumors and no predictive value was observed. Because of limited number of surgically resected tumors obtained, we couldn’t proceed exploratory proteomics analysis nor evaluate predictive value of neuropilin expression.
Conclusion:
In this comprehensive predictive biomarker analysis, follistatin and leptin in blood were identified as potential biomarker candidates for E+B therapy.
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