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C. Tsai
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-064 - A Phase II Study of Gemcitabine-Cisplatin plus Necitumumab for Stage IV Sq-NSCLC (ID 927)
09:30 - 09:30 | Author(s): C. Tsai
- Abstract
Background:
To report the efficacy and safety results from a study of necitumumab (N), manufactured under process D, modified from Process C, used in the pivotal SQUIRE study, in combination with gemcitabine (G) plus cisplatin (C) as first-line treatment in patients with advanced squamous non-small cell lung cancer (Sq-NSCLC). (NCT01788566)
Methods:
This was an open-label, single-arm, multicenter, phase II study in patients with advanced Sq-NSCLC. Patients were enrolled who were aged ≥18 years and had measurable, pathologically confirmed stage IV Sq-NSCLC without prior chemotherapy. Patients had ECOG-PS 0-1, adequate organ function, and life expectancy of ≥12 weeks. Patients received N (800 mg iv, Days 1 and 8) plus GC (G=1250 mg/m² iv, Days 1 and 8; C=75 mg/m² iv, Day 1) each 3-week cycle for up to 6 cycles. Patients with at least stable disease (SD) could continue to receive N alone until progressive disease (PD) or other discontinuation criteria. Primary endpoint was objective response rate (ORR) based on RECIST1.1. Secondary endpoints included overall survival (OS), progression-free survival (PFS), disease control rate (DCR), change in tumor size (CTS; % improvement in lesions), and safety.
Results:
Patients (N=61), median age 65 years, heavy metastatic disease burden; approximately 70% of the patients had metastases to ≥ 2 organ systems. Efficacy results, including an ORR of 48.1% are shown in the Table. Survival and PFS findings were similar to those reported in the SQUIRE study in the GC+N arm (SQUIRE results: median OS of 11.5 months, 1-year survival rate of 47.7%, and median PFS of 5.7 months). Median duration of treatment was 12 weeks (4 cycles) for G and C and 16 weeks (5 cycles) for N; the median relative dose intensity was 85% for G and 93% for C and N. Twenty-eight (46%) patients continued on single-agent N (median: 4 cycles). Skin reactions (n=49; 80.3%) and hypomagnesemia (n=21; 34.4%) were the most commonly reported adverse events of special interest (AESIs, all grades). AESI ≥ Grade 3 were skin reactions (n=8; 13.1%), thromboembolic events (n=7; 11.5%), hypomagnesemia (n=6; 9.8%), and hypersensitivity/ IRR (n=3; 4.9%). There were 27 deaths (20 due to PD and 7 due to AEs [5 had no causal relationship to study drug]) at the time of data cut-off.Table. Efficacy Results
N=61 ORR*† (CR+PR), n (%) [95% CI] 26/54 (48.1)† [34.34–62.16] CR 0 PR, n (%) 26/54 (48.1)† SD 18 (29.5) PD 9 (14.8) Not evaluable 1 (1.6) Not assessable 7 (11.5) DCR CR+PR+SD, n (%) [95% CI] 44 (81.5)† [68.57–90.75] Median OS, months (95% CI) 11.7 [7.59–NA] 1-year survival rate, % (95% CI) 47.6% [30.20–63.08] Median PFS, months (95% CI) 5.6 [3.68–6.87] Median CTS, (%) 42.1 *Assessed by investigators †Patients who had a post-baseline radiological assessment, n=54
Conclusion:
The efficacy results and the safety profile, with N manufactured under process D, are consistent with what is expected for this combination as first-line therapy of patients with metastatic Sq-NSCLC.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-021 - Non-Inferior Progression Free Survival in NSCLC Patients Sensitive to EGFR TKI Receiving Low Dose versus Regular Dose of Gefitinib or Erlotinib (ID 2543)
09:30 - 09:30 | Author(s): C. Tsai
- Abstract
Background:
Preclinical data demonstrate that the T790M clone is associated with a growth disadvantage in the absence of TKI selection. With selection stress of standard dose of TKI, T790M cells may become a dominant population. In a mathematical model, high pulse dose combined with continuous low-dose of TKI could delay the emergence of resistant clone of T790M. Clinically, some patients use lower dose of EGFR TKI due to various reasons such as toxicity. The treatment outcome in terms of PFS in this group of patients has not been reported. Whether the PFS would be impaired due to dose adjustment or unaffected and even better to support above theory may need further clarification.
Methods:
A retrospective cohort study was conducted to recruit patients with advanced NSCLC from 1997/1 to 2014/12 in a regional teaching hospital. Inclusion criteria were patients whose tumors were either tested to have sensitizing mutations of EGFR using highly sensitive methods or clinically responsive to EGFR TKI using Jackman’s criteria. Patients having titrated dose of TKI to two-thirds or less for more than 6 months were assigned to low-dose (LD) group. The standard-dose (control) group includes patients receiving daily 250 mg of Gefitinib or 150 mg of Erlotinib during whole course of treatment, matched with sex and age to LD group. The primary outcome was PFS. Secondary outcome was overall survival (OS).
Results:
LD group includes 20 patients and control group 80 patients. Patients using LD treatment were mostly due to intolerable side effects with standard dose (n=18, 90%). The median PFS was 15.4 months in the LD group and 9.3 months in control (hazard ratio 0.45, 95% CI of 0.29-0.71; p=0.018). The median OS was 31.5 months in LD and 31.4 months in control (hazard ratio 0.99, 95% CI 0.49-1.98; p=0.98). In the subgroup of Gefitinib treatment, the median PFS was 17.9 months in LD and 8.1 months in control (hazard ratio 0.35, 95% CI 0.19-0.62; p=0.0037). In patients receiving Erlotinib, median PFS was 15.3 months in LD and 12.1 months in control (hazard ratio 0.67, 95% CI 0.33-1.37; p=0.2652). Median OS was similar in LD and control in either subgroup of Gefitinib or Erlotinib.
Conclusion:
This study showed that lower dose of EGFR-TKI treatment is a non-inferior strategy for patients sensitive to EGFR TKI. Better PFS in the LD group of Gefitinib-treated patients support the theory of delayed emergence of resistant clone. Since 150 mg of Erlotinib is at its maximum tolerated dose, a dose choice of no more than optimum biologic dose may be needed to gain such benefit as Gefitinib. Larger-scale studies would be needed to confirm this finding.
