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J. Fiore
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-028 - A Phase II Trial of Albumin-Bound Paclitaxel and Gemcitabine in Patients with Untreated Stage IV Squamous Cell Lung Cancers (ID 8556)
09:30 - 09:30 | Author(s): J. Fiore
- Abstract
Background:
Therapeutic options for squamous cell lung cancer (SQCLC) patients remain limited. Platinum-based chemotherapies, which have been the standard first-line treatments for nearly 20 years, are associated with ORR=30-40%, median PFS=4-5.7mo, and median OS=9-11.5mo. We previously reported the results of a phase 1/2 trial of albumin-bound paclitaxel (ABP) in 40 patients with untreated stage IV NSCLC, noting an ORR of 30%, median PFS of 5mo, and median OS of 11mo (Rizvi JCO 2008). These data suggest that platinum adds little when coupled to ABP. Conversely, compelling evidence of anti-tumor synergy between gemcitabine and ABP was recently demonstrated by Frese et al. who showed that ABP downregulates cytidine deaminase (which inactivates gemcitabine), leading to increased intratumoral [gemcitabine] (Cancer Disc 2012). Based on these data, we sought to assess the efficacy of ABP + gemcitabine in patients with SQCLC.
Method:
This is a phase II trial of ABP (100mg/m[2]) + gemcitabine (1000mg/m[2]) given on D1, D8, D15 of an every 4 week cycle (A1) in patients with untreated stage IV SQCLC. Patients received up to 6 cycles and were followed thereafter (A1). The primary endpoint is best objective response (RECIST 1.1). The study utilizes a Simon two-stage design with H0=25% (6/17 responses) and H1=45% (16/41 responses). After clearing the first stage, the study was amended to a 3 week cycle (D1, D8 treatment); to allow ABP + gemcitabine until progression; and to allow maintenance ABP to begin after C4 for tolerability (A2). PFS, TTP, and OS were calculated using the Kaplan-Meier method. Patients underwent NGS by MSK-IMPACT for genotype-phenotype correlation.
Result:
N=17 patients (14 evaluable) were treated on A1 and, to date, N=3 patients (2 evaluable) have been treated on A2. Median age=70, female=30%, median KPS=90%, smokers=90%, median pack years=32. Median cycles of therapy in A1=4. Grade ≥3 related AEs included: peripheral neuropathy (5%); diarrhea (5%); elevated ALT (5%); anemia (15%); and decreased neutrophils (25%). Three patients (15%) experienced a related SAE including G3 decreased WBC, G3 diarrhea, and G3 lung infection. There was 1 unrelated death as a result of complications from a G3 mechanical fall. ORR in A1=50% (7/14 PRs). ORR in A2=100% (2/2 PRs). ORR in A1+A2=56% (9/16 PRs). SD=6 (38%) and PD=1 (6%). Median PFS=5.8mo; TTP=6.9mo; OS=13.3mo.
Conclusion:
ABP + gemcitabine has promising efficacy and is relatively well-tolerated, particularly when compared to platinum regimens. Accrual to the study is ongoing and updated data, including NGS correlates, will be presented.
