Virtual Library
Start Your Search
W.K. Hong
Author of
-
+
MO18 - NSCLC - Targeted Therapies IV (ID 116)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:L. Horn, J. Wolf
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Auditorium B, Level 1
-
+
MO18.06 - BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 1949)
16:45 - 16:50 | Author(s): W.K. Hong
- Abstract
- Presentation
Background
Effective therapeutic strategies for mutant KRAS and other biomarkers of resistance in refractory NSCLC remain an unmet medical need, while a personalized medicine approach is increasingly adopted in NSCLC guided by tumor molecular profiling. The BATTLE-2 clinical study is using EGFR, PI3K/AKT and MEK inhibitors and is designed to identify biomarkers for optimal patient selection for these therapies (ClinicalTrials.gov NCT01248247).Methods
This is a four-arm, open-label, multi-center, biopsy-driven, adaptive randomization, phase II clinical trial in NSCLC pts that failed at least 1 prior line of therapy. Patients are adaptively randomized to 4 arms: erlotinib, erlotinib plus the AKT inhibitor MK-2206, MK-2206 plus the MEK inhibitor selumetinib, and sorafenib. The primary objective is 8-week disease control rate (DCR). The trial is conducted in 2 stages. In Stage 1, 200 evaluable pts are adaptively randomized (AR) based on observed 8-week DCR and KRAS mutation status while predictive biomarkers are being developed by means of gene expression profiling, targeted next generation sequencing and protein expression. EGFR sensitizing mutations and EML4/ALK translocation in pts that are erlotinib and crizotinib naïve are exclusion criteria, while erlotinib resistant patients are excluded from erlotinib monotherapy. In Stage 2, the AR model is refined to include the most predictive biomarkers tested in Stage 1, with subsequent Stage 2 AR based on the new algorithm, to a total of 400 evaluable pts. Selection of Stage 2 single and/or composite markers follows a rigorous, internally and externally reviewed statistical analysis that follows a training, testing methodology with validation in stage 2 of the trial. All Stage 1 and 2 randomization biomarker assays are CLIA-certified.Results
286 pts have been enrolled, 236 biopsies performed,172 pts randomized, and 167 pts treated. 144 pts are evaluable for the 8-week DCR endpoint. Within the randomized pts group KRAS mutation rate is 22.8%, and EGFR mutation rate 14.8%, while 36.3% patients have been previously treated with erlotinib. Treatment is well tolerated with no unanticipated toxicity.Conclusion
Accrual updates, demographics, and further details will be presented at the meeting. (Supported by NCI R01CA155196-01A1)Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
O02 - NSCLC - Combined Modality Therapy I (ID 111)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Combined Modality
- Presentations: 1
- Moderators:W.E.E. Eberhardt, C.J. Langer
- Coordinates: 10/28/2013, 10:30 - 12:00, Parkside Ballroom B, Level 1
-
+
O02.03 - Value of Adding Erlotinib to Thoracic Radiation Therapy with Chemotherapy for Stage III Non-Small Cell Lung Cancer: A Prospective Phase II Study (ID 2436)
10:50 - 11:00 | Author(s): W.K. Hong
- Abstract
- Presentation
Background
The molecular basis for radiation resistance seems to involve an enhanced survival response with increased capacity for DNA repair and suppressed apoptosis. Both properties are controlled in part by upstream signal transduction pathways triggered by activation of the epidermal growth factor receptor (EGFR). Hypothesizing that the response of non-small cell lung cancer (NSCLC) to current standard chemoradiotherapy can be improved through the addition of therapy targeted to the epidermal growth factor receptor (EGFR), we undertook a single-institution phase II trial to test whether adding the EGFR tyrosine kinase inhibitor (TKI) erlotinib to concurrent chemoradiation therapy for previously untreated, locally advanced, inoperable NSCLC would improve survival and response rates without increasing toxicity.Methods
Forty-eight patients with previously untreated NSCLC received radiation (63 Gy/35 fractions) on Monday‒Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin AUC=2) given every Monday and erlotinib (150 mg orally 1/d) Tuesday–Sunday for 7 weeks, followed by two cycles of consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were toxicity; response, overall survival (OS), and disease control rates; and whether any endpoint differed by EGFR mutation status.Results
Of 46 patients (96%) evaluable for response, 40 were former or never smokers; 23 had adenocarcinoma; and 41 were evaluable for EGFR mutations (37 wild-type [wt] and 4 mutations [all adenocarcinomas]). Median time to progression was 14.5 months and did not differ according to EGFR status. Toxicity was acceptable (no grade 5, one grade 4, and eleven grade 3). Fourteen patients (31%) had complete responses (3 mutations and 11 wt), 24 (52%) partial (20 wt and 4 unknown EGFR mutation status), and 8 (18%) had stable or progressive disease (6 wt, 1 mutation and 1 unknown EGFR mutation status); 3 patients with mutations (75%) had complete response vs. 11 wt (30%) (p=0.07 for EGFR mutation vs wt groups). For alive patients, the median follow-up was 44.7 months’ follow-up (range, 29.3–54.6 months). OS rates were 82.6% at 1 year, 67.4% at 2 years, 48.5% at 3 years, and 32.2% at 4 years and did not differ by mutation status (wt vs mutation, p=0.17). For all patients the median follow-up was 30.6 months’ follow-up (range, 3.4–54.6 months). 14 patients were free from progression and 32 had local failure, distant failure, or both. Eleven of the 27 distant failures were in the brain (7 wt, 3 mutation, 1 unknown; P=0.04); the local control rate was 75% among the 4 patients with EGFR mutations. Median time to progression was 13.6 months (95% confidence interval 10.2-20) and did not differ by EGFR status (wt vs mutation p=0.39).Conclusion
Overall survival was promising, but time to progression was disappointing. Toxicity was acceptable. The prevalence of distant failures underscores the need for more effective systemic therapy, perhaps including maintenance EGFR-TKI for patients with mutated EGFR.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
