Virtual Library
Start Your Search
E.S. Kim
Author of
-
+
P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P2.03b-053 - Role of KRAS Mutation Status in NSCLC Patients Treated on SWOG S0819, a Phase III Trial of Chemotherapy with or without Cetuximab (ID 6113)
14:30 - 14:30 | Author(s): E.S. Kim
- Abstract
Background:
The S0819 phase III study of chemotherapy and bevacizumab (by patient/physician choice) with or without cetuximab in NSCLC showed no benefit from the addition of cetuximab, either overall or within the EGFR FISH-positive subset. Secondary analysis suggested an overall survival benefit in EGFR FISH-positive squamous cell carcinoma (SCC) (Herbst WCLC 2015, Hirsch ASCO 2016). In colorectal cancer (CRC), benefit from EGFR monoclonal antibodies such as cetuximab is limited to patients with RAS wild type (WT) tumors; however, in NSCLC, previous studies have not been sufficiently powered to make this determination. We prospectively incorporated KRAS mutation testing in S0819 to determine whether it predicts cetuximab efficacy. Since KRAS mutations are rare in SCC, we focused this analysis on nonSCC.
Methods:
KRAS mutation status was determined using the Therascreen KRAS test (Qiagen), conducted in a CLIA-certified diagnostic laboratory at the UC Davis Comprehensive Cancer Center. This test is FDA-approved for KRAS diagnostics in metastatic CRC, and identifies 6 mutations at codon 12 (G12A,D,R,C,S,V) plus G13D.
Results:
KRAS mutation status was available for 448 nonSCC patients, and mutations were identified in 150 cases (33%). Amino acid substitutions matched the expected distribution for a NSCLC population, with 52% harboring G12C and 17% with G12V. No significant differences were observed between KRAS-mut and WT populations for PFS (HR=1.15 (0.94-1.42); p=0.18) or OS HR=1.10 (0.89-1.37); p=0.39). Furthermore, no differences in outcomes between arms were observed based on KRAS mutation status (Table). The KRAS WT, EGFR FISH+ molecular subset (hypothetically the most likely subgroup to benefit from cetuximab) showed no statistical differences in outcomes between arms. Figure 1
Conclusion:
Determination of KRAS mutation status did not identify a subgroup of nonSCC patients with differential outcome from addition of cetuximab to front-line chemotherapy. In contrast to CRC, cetuximab does not appear to confer benefit to patients with KRAS-WT nonSCC NSCLC.
-
+
P3.02a - Poster Session with Presenters Present (ID 470)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02a-013 - Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized Phase 2 Trial (ID 4046)
14:30 - 14:30 | Author(s): E.S. Kim
- Abstract
Background:
Brigatinib, an investigational next-generation ALK inhibitor, has yielded promising activity in crizotinib-treated ALK+ NSCLC patients in a phase 1/2 trial (NCT01449461). As responses and adverse events (AEs) varied with starting dose, two brigatinib regimens are under evaluation in ALTA (NCT02094573).
Methods:
Patients with crizotinib-refractory advanced ALK+ NSCLC were randomized 1:1 to receive brigatinib at 90 mg qd (arm A) or 180 mg qd with a 7-day lead-in at 90 mg (arm B) and stratified by presence of brain metastases at baseline and best response to prior crizotinib. Primary endpoint was investigator-assessed confirmed ORR per RECIST v1.1.
Results:
222 patients were enrolled (arm A, n=112/arm B, n=110). Median age (A/B) was 51/57 years, 55%/58% were female, 74%/74% previously received chemotherapy, and 71%/67% had brain metastases. As of February 29, 2016, 64/112 (57%) patients in arm A and 76/110 (69%) patients in arm B were receiving brigatinib; median follow-up was 7.8/8.3 months. The Table shows investigator-assessed endpoints by arm and subgroup for select baseline characteristics. Independent review committee–assessed endpoints (A/B, n=112/n=110; as of May 16, 2016): confirmed ORR 48%/53%, median PFS 9.2/15.6 months. Any-grade treatment-emergent AEs (≥25% overall frequency; A/B, n=109/n=110 treated): nausea (33%/40%), diarrhea (19%/38%), headache (28%/27%), cough (18%/34%); grade ≥3 events (excluding neoplasm progression; ≥3% frequency): hypertension (6%/6%), increased blood CPK (3%/9%), pneumonia (3%/5%), increased lipase (4%/3%). A subset of pulmonary AEs with early onset (median onset: Day 2) occurred in 14/219 (6%) treated patients (3%, grade ≥3); 7/14 patients were successfully retreated. No such events occurred after escalation to 180 mg in arm B.
Conclusion:
In each arm, brigatinib yielded substantial responses and prolonged PFS, with an acceptable safety profile. 180 mg with 90 mg lead-in was not associated with increased early pulmonary events and showed a consistent improvement in efficacy, compared with 90 mg, particularly with respect to PFS.Investigator-Assessed Endpoints by Arm and Subgroup
Confirmed ORR, n/N(%) Median PFS, months Arm A B A+B A B A+B All patients 50/112(45) 59/110(54) 109/222(49) 9.2 12.9 11.1 Prior chemotherapy Yes 35/83(42) 44/81(54) 79/164(48) 8.8 12.9 11.8 No 15/29(52) 15/29(52) 30/58(52) 9.2 8.1 9.2 Race Asian 18/39(46) 18/30(60) 36/69(52) 8.8 11.1 11.1 Non-Asian 32/73(44) 41/80(51) 73/153(48) 9.2 12.9 11.8 Brain metastases at baseline Yes 31/80(39) 43/74(58) 74/154(48) 9.2 11.8 11.1 No 19/32(59) 16/36(44) 35/68(51) 7.4 15.6 15.6 Best response to prior crizotinib Partial+complete 36/71(51) 47/73(64) 83/144(58) 11.1 15.6 15.6 Other 14/41(34) 12/37(32) 26/78(33) 7.4 12.9 9.2 ORR=objective response rate PFS=progression-free survival
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-023 - Physician Patterns of Care in Patients with EGFR Mutation+ NSCLC: An International Survey into Testing and Treatment Choice (ID 6067)
14:30 - 14:30 | Author(s): E.S. Kim
- Abstract
Background:
(Applied for Late-Breaking Abstract Status) IASLC guidelines recommend EGFR mutation testing should be performed at diagnosis of advanced NSCLC to guide treatment decisions. In 2015 an international survey concluded that not all patients were tested or received test results before treatment initiation. This varied between countries and across regions. The aim of a follow-up survey in 2016 was to assess testing rates and HCP treatment choice in advanced NSCLC to identify improvements and changes compared to 2015.
Methods:
Online survey of 707 oncologists in 11 countries (Canada, China, France, Germany, Italy, Japan, South Korea, Spain, Taiwan, UK, USA) between July - August 2016. China was newly added in 2016. For better comparison with 2015 results, China was excluded from the primary results focus
Results:
Globally*, physicians requested EGFR mutation testing prior to first-line therapy of stage IIIb/IV NSCLC in 80% of patients. However, 18% of ordered tests were not received prior to deciding first-line therapy; an improvement on 2015 with 23%. Excluding histology, the main reasons for not testing prior to first-line therapy were insufficient tissue, poor performance status and long turnaround time. While turnaround time significantly reduced year-on-year (2016: 21% vs. 2015: 30%), globally* 24% of patients receive test results after more than 10 business days. Globally* 79% (2015: 80%) of patients with mutations (M+) were treated with tyrosine kinase inhibitors (TKIs), with large country variations on treatment preference (minimum 68% Germany; maximum 98% Taiwan). Prolonging of survival/extending life (54%*) was deemed the most important therapy goal in first-line treatment. 74%* of physicians stated that a clinically relevant increase in overall survival was the most important treatment attribute when choosing a first-line therapy, closely followed by an increase in progression-free survival (68%) and strong improvement of health related quality of life (66%). Perceived differences between TKIs were reported by 49% of physicians. Further detail will be presented at the congress. *Global figures excluding China
Conclusion:
While year-on-year improvements in EGFR testing rates, and availability of test results prior to first-line therapy are seen, a large proportion of EGFR M+ NSCLC patients are still not receiving targeted treatment with TKIs based on mutation status. Incomplete implementation of guidelines is still observed. The main barriers to testing, including receiving results in time, must be addressed if treatment equality for all eligible patients can be achieved. Physician education and closer guideline concordance are key steps to further improve outcomes.
