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G.R. Pond
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MINI 04 - Clinical Care of Lung Cancer (ID 102)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:L. Gaspar, V. Westeel
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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MINI04.14 - Comparative Survival in Patients with Brain Metastases from Non-Small Cell Lung Cancer Treated before and after Implementation of Radiosurgery (ID 2862)
18:00 - 18:05 | Author(s): G.R. Pond
- Abstract
- Presentation
Background:
Survival after a diagnosis of brain metastases (BM) in non-small cell lung cancer (NSCLC) is generally considered poor. We previously reported median survival of approximately 4 months in a cohort of patients treated with whole brain radiotherapy (WBRT), the standard of care in many centres. Since that time, we implemented a program of stereotactic radiosurgery (SRS), based on randomized trials and large prospective series, supporting WBRT + SRS or SRS alone in selected patients. The current study examined survival and prognostic factors in a consecutive cohort of NSCLC BM patients after the introduction of an SRS program.
Methods:
A retrospective review of 167 NSCLC patients referred with BM to a tertiary cancer centre from 2010-2012 (NEW cohort) was undertaken. These data were compared to a prior cohort of 91 patients treated between 2005 and 2007 (OLD cohort). Summary statistics were used to describe the patient characteristics as well as outcomes. The Kaplan-Meier method was used to calculate time-to-event outcomes for overall survival (OS), from the time of BM diagnosis. Cox proportional hazards regression was used to investigate factors prognostic for outcomes. An optimal model was constructed using forward stepwise selection, and tests were two-sided with a p-value <0.05 deemed statistically significant.
Results:
Overall survival from diagnosis of BM (median 4.3 months NEW vs 3.9 months OLD p=0.74) was not significantly different between cohorts. A univariate analysis of the NEW cohort demonstrated significant differences in OS between treatment groups (SRS, WBRT + SRS, WBRT or no treatment), in terms of female gender (p=0.034), lack of neurological symptoms (p=0.001), number of BM (p<0.001), GPA (p=0.001), and ECOG status at BM (p=0.009). Treatment regimen with SRS or WBRT + SRS was significant as a prognostic factor for OS as well (p<0.001). Results were similar if one excluded the no treatment group. As some factors were not collected in the OLD cohort, a separate model was constructed including only data available from both cohorts. After adjusting for factors included in the optimal model, cohort was not statistically significant for OS (hazard ratio=1.03, 95% CI 0.90-1.59; p =0.88). There was a trend towards improved OS in the NEW vs OLD cohorts in patients <50 years of age (median 11.8 vs 7.5 months, p=0.39) and 50-59 years of age (median 7.8 vs 3.7 months, p=0.052); this trend reversed to favour the OLD vs NEW cohort in patients >70 (4.3 vs 2.8 months, p=0.01). This was coincident with increased uptake of chemotherapy (p<0.001) and better ECOG status (p=0.007) in younger age groups in the NEW versus OLD cohort.
Conclusion:
There has been no improvement in survival of NSCLC patients with BM, following the implementation of SRS. Selected patients (younger age, female gender, good fitness, fewer brain metastases) appear to demonstrate improved OS with SRS. However, this may also reflect a better natural history of the disease, or a greater tendency to offer them systemic therapy, in addition to receipt of SRS.
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.01 - A Phase II Study of Dovitinib in Previously-Treated Malignant Pleural Mesothelioma: The Ontario Clinical Oncology Group DOVE-M Trial (ID 1302)
16:45 - 16:50 | Author(s): G.R. Pond
- Abstract
- Presentation
Background:
Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFR.
Methods:
This open-label multicentre phase II trial enrolled consenting adult patients with advanced, histologically-confirmed MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy. Patients were ECOG PS < 2 and had adequate end-organ function. Dovitinib was administered orally at 500 mg/day for 5 days on, 2 days off; cycle length was 28 days. Two dose reductions (to 300 mg) for toxicity were permitted. Response was assessed every 2 cycles using RECIST 1.1 criteria modified for MPM. Correlative studies included FGFR-1 amplification on archival tumour and serum samples for circulating angiogenesis factors. Pre- and cycle 1 day 15 on-treatment diffusion-weighted pleural MRI was evaluated for its potential as an early marker of drug effect. The primary end-point was the proportion of patients progression-free at 3 months (PF3). A two-stage design was used: H0: 3-month PFS=40% versus HA: 3-month PFS=65% (roughly corresponding to a median PFS of 4.5 months), with α=0.05, β=0.20. If 6 of 12 PF3 in stage I, an additional 14 patients would be enrolled, with dovitinib of interest if > 15 of 26 PF3.
Results:
12 patients (10 males, median age 67) were enrolled. The median number of cycles administered was 2.5 (range 1-8). Commonly observed and / or grade 3 at least possibly related adverse events (any grade / grade 3, %): diarrhea (67 / 0%) vomiting (50 / 0%) fatigue (42 / 8 %), nausea (42 / 8 %), rash (0 / 17 %), syncope / generalized muscle weakness / elevated ALT (0 / 8 % each). No hyperphosphatemia was observed. 7 patients had at least one dose interruption (5 in cycle 1) and 5 had a dose reduction (1 to 300 mg); median dose intensity during cycles 1 and 2 was 80 %. 3 patients discontinued due to clinical progression by day 1 cycle 2. Best response: 1 unconfirmed PR, 4 SD, 2 PD and 4 inevaluable (3 with clinical PD; 1 intercurrent illness). The median PFS was 2.6 months and the median OS was 4 months. PF3 was 50%; although the criterion for proceeding to stage II accrual was met, the trial was halted due to a combination of minimal activity with several early progression events and poor tolerability in this patient population.
Conclusion:
Dovitinib has minimal activity and a toxicity profile comparable to other VEGFR inhibitors in previously-treated MPM; it is not clear if FGFR is effectively targeted. Correlative studies are ongoing and may help to clarify the role of the FGFR in MPM. [NCT01769547].
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