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Y. Nakamura
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MINI 31 - ALK (ID 158)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:S. Malik, I. Ou
- Coordinates: 9/09/2015, 18:30 - 20:00, Mile High Ballroom 1a-1f
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MINI31.09 - Association of Crizotinib Toxicity with Pharmacokinetics and Pharmacogenomics in Non-Small Cell Lung Cancer Harboring ALK Fusion Gene (ID 464)
19:15 - 19:20 | Author(s): Y. Nakamura
- Abstract
- Presentation
Background:
Crizotinib, a standard care for advanced ALK-positive NSCLC, is a substrate for ABCB1-encoded P-glycoprotein, and is primarily metabolized by CYP3A4/5. The most common adverse events (AEs) are visual disorder, gastrointestinal disorders, and elevated transaminase levels. Serious AEs such as grade (Gr) ≥ 3 elevated transaminase levels and interstitial lung disease (ILD) occasionally develop.
Methods:
ALK-positive NSCLC patients were enrolled in cohort A (enrollment before starting crizotinib therapy) or cohort B (enrollment during crizotinib therapy). Trough concentrations of crizotinib at steady state were measured using LC/MS/MS and ABCB1 polymorphisms were analyzed. We evaluated clinically significant AEs, defined as Gr 4 hematological toxicity, Gr ≥ 3 non-hematological toxicity, or any ILD. AEs during 8 weeks were also evaluated prospectively on the patients enrolled in cohort A.
Results:
A total of 78 patients at 17 institutions were enrolled. In cohort A (n = 47), AEs which occurred in more than 40% of patients during 8 weeks were ALT increased (75.0%), visual disorder (47.2%), anorexia (45.5%), nausea (45.5%), and AST increased (43.2%). In both cohorts (n = 75), 26 clinically significant AEs (n = 25) were observed: Gr ≥ 3 elevated transaminase level (14.7%), ILD (4.0%), Gr 4 neutropenia (4.0%), Gr 3 thromboembolic event (4.0%), Gr 3 esophagitis (2.6%), and Gr 3 QTc prolongation (2.6%). There was one treatment-related death (1.3%) due to ILD. Clinically significant AEs tended to occur more frequently in females than males, albeit without significance (38.4% vs. 19.2%, respectively; p = 0.09). Blood samples for trough concentrations of crizotinib at steady state were collected from 63 patients. The geometric mean of trough concentrations were 396 (95% CI, 325-483) ng/ml in male and 395 (95% CI, 329-474) ng/ml in female, respectively (p=0.569, Mann-Whitney U test). No clinical factors including gender, weight, body surface area, and age which influenced trough concentrations or AEs of crizotinib were identified. Moreover, the trough concentration of crizotinib was not significantly different between patient with clinically significant and without (429 [95% CI, 361-509] ng/ml vs. 378 [95% CI, 313-456] ng/ml, respectively [p=0.365]).
Conclusion:
In this multicenter study, we observed crizotinib AEs as previously reported. Clinically significant AEs tended to occur more frequently in females than males, albeit without significance. Furthermore, we will present the association of clinically significant AEs and trough concentration with ABCB1 polymorphism.
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P2.11 - Poster Session/ Palliative and Supportive Care (ID 230)
- Event: WCLC 2015
- Type: Poster
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.11-003 - Changes in Quality of Life Through the Early Intervention by a Palliative Care Team for Patients with Advanced Lung Cancer (ID 1098)
09:30 - 09:30 | Author(s): Y. Nakamura
- Abstract
Background:
The change in quality of life (QOL) through the early intervention by a palliative care team was analyzed in patients with advanced lung cancer. The contrast between patients’ own evaluation on their QOL and their QOL estimated by their attending physicians was examined as well.
Methods:
The eligibility criteria were newly-diagnosed Japanese patients with stage IV lung cancer, whose ages were over 20- years old, whose Eastern Cooperative Oncology Group Performance Status were from 0 to 3, and those who had written informed consent. For the patients and attending physicians, QOL questionnaires, which were in line European Organization for Research and treatment of Cancer Quality of Life Questionnaire-Core15 （EORTC QLQ c-15）, were conducted at the time of the enrollment and twelve weeks later. The primary endpoint was a change in global QOL score, which ranged from 0 (worst) to 100 (best), after the twelve-week intervention.
Results:
58 patients out of 96 who were newly diagnosed as stage IV lung cancer were enrolled in this study. 43 patients had the QOL evaluation after twelve weeks. One patient withdrew consent, one patient moved to another hospital and other thirteen patients died during the intervention period. The primary endpoint improved by more than 25% that was originally anticipated (50 points at the enrollment, 64.7 points after the intervention.). All of the following factors including emotional state, nausea, vomiting, pain, constipation improved by more than 25% similarly to the primary endpoints, although other QOL factors showed a slight improvement or no change. While the difference between the QOL score by the patients and the physicians was apparent at the beginning the intervention, it became smaller by every measurement after twelve weeks. In Japan, Palliative care units (PCUs) have a role of hospices as well, and there are not enough number of them, to meet the entire needs for the end-of-life care. Some patients end up dying while on the waiting lists of PCU. Less percentage of patients who had early palliative care (EPC) died while waiting PCU admission, as compared with other cancer patients who applied for PCU during the same period as the present study. (12.5 % vs 30.4 %) In addition, duration of best supportive care in patients were extended approximately one month, as compared with past patients with stage IV lung cancer in undergoing EPC.(108.7day vs 78day)
Conclusion:
QOL improved in studied Japanese patients after the early interventions by the palliative care team. This result may indicate that discrepancy of QOL evaluation between the patients and physicians was lessened due to the early intervention by the palliative care team, which is considered to have fostered the improvement of the overall QOL. It was suggested that such intervention might support the patients in decision making for end-of-life-care.
