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Joel W. Neal
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MA15 - Colliding Approaches - EGFR and Immunotherapy (ID 916)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 13:30 - 15:00, Room 107
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MA15.12 - Discussant - MA 15.09, MA 15.10, MA 15.11 (ID 14644)
14:45 - 15:00 | Presenting Author(s): Joel W. Neal
- Abstract
- Presentation
Abstract not provided
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-71 - Co-Mutations, Natural History, and Outcomes of BRAF-Mutated Non-Small Cell Lung Cancer at a Single Academic Cancer Center (ID 12392)
16:45 - 18:00 | Author(s): Joel W. Neal
- Abstract
Background
Mutations in the BRAF oncogene occur in 2-4% of cases of non-small cell lung cancer (NSCLC). Based on recent trials, combination therapy targeting BRAF and MEK within the MAPK pathway is now approved for BRAF V600E-mutated NSCLC. As BRAF mutations occur infrequently, however, the natural disease history of BRAF-mutated NSCLC remains an area of ongoing study. Our aim was to describe the natural history and outcomes of patients with BRAF-mutated NSCLC seen at our institution.
a9ded1e5ce5d75814730bb4caaf49419 Method
An IRB-approved protocol was used to query the Stanford Cancer Registry and Stanford Cancer Institute Research Database (SCIRDB) for patients with BRAF-mutated NSCLC presenting between January 1, 2006 and July 31, 2015. Each patient chart was then retrospectively reviewed.
4c3880bb027f159e801041b1021e88e8 Result
The cohort included 18 patients (median age 66.5 years, 72% male). V600E mutations were most common (72%; 13/18) while non-V600E mutations included G469A (n = 2), G466V, K601E, and V600_W604delinsR. Most patients (69%; 9/13) with V600E mutations were light or never smokers whereas most patients with non-V600E mutations (80%; 4/5) were heavy smokers (>15 pack-years). Secondary mutations occurred most commonly in TP53 (28%; 5/18). With respect to treatment, no patients received BRAF-targeted therapy upfront. Median duration of first-line platinum-based chemotherapy was 9 months (range 1.5-21.5). In the second-line setting, median duration of chemotherapy was 6 months (range 1-52) and median duration of BRAF-targeted therapy was 5.5 months (range 5.5-6.5). Median overall survival of the entire cohort was 34.8 months. Median survival from the onset of metastases (n = 16) was 26.8 months (range 2-130.5) (Table). Among patients diagnosed with stage III-IV disease, survival at 2-years was 53%, with many showing slow progression and control of oligometastatic or intrathoracic disease with systemic therapy or localized radiation.
Stage BRAF Mutation Co-occurring Mutations Overall Survival (months) Post-Metastases Survival (months) 1 IA V600E None 83.5+ 39.5+ 2 IIIB V600E None 8.5 7 3 IV G469A None 37 37 4 IIIB V600E None 40+ 26.5+ 5 IIIA G469A TP53 41 27 6 IV V600E None 14 14 7 IV V600E None 130.5 130.5 8 IIA V600E None 65 NA 9 IV V600E CTNNB1 2 2 10 IV V600E PIK3CA 47.5 47.5 11 IIIA G466V Multiple (incl. TP53) 39.5 32.5 12 IA V600E TP53 32.5+ NA 13 IV V600_W604 None 22.5 22.5 14 IV V600E None 28 28 15 IV V600E Multiple (incl. TP53) 13.5 13.5 16 IV V600E None 88.5 88.5 17 IV K601E TP53 6.5 6.5 18 IV V600E NKX2-1 19.5 19.5
8eea62084ca7e541d918e823422bd82e Conclusion
BRAF-mutated NSCLC can be associated with prolonged survival in some patients. Future research should aim to identify factors predicting longer outcomes.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-44 - Safety, PK, and Preliminary Antitumor Activity of the Oral EGFR/HER2 Exon 20 Inhibitor TAK-788 in NSCLC (ID 12373)
16:45 - 18:00 | Presenting Author(s): Joel W. Neal
- Abstract
Background
TAK-788 (AP32788) is an investigational tyrosine kinase inhibitor (TKI) with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. We report early results of a phase 1/2 first-in-human, open-label, multicenter study of TAK-788 (NCT02716116).
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with advanced non-small cell lung cancer (NSCLC) refractory to standard therapy received daily oral doses (5–120 mg) of TAK-788 in the ongoing dose-escalation phase (3+3 design). Preliminary antitumor activity (by RECIST v1.1), safety, and PK are reported for patients who received ≥1 dose.
4c3880bb027f159e801041b1021e88e8 Result
As of 8-Sep-2017, 34 patients (median age, 60 y; female, 65%; ≥2 prior anticancer therapies, 88%; Table) were treated with TAK-788; 10 remain on treatment at data cutoff. AUC0‑24,ss increased in a dose-proportional manner over the dose range evaluated; the effective t1/2 was ~16 (range 6–28) h. The most common treatment-emergent AEs (TEAEs; ≥20%) were diarrhea (47%), nausea (26%), and fatigue (21%). Grade ≥3 TEAEs in ≥2 patients (excluding disease progression) were dyspnea (n=3, 9%) and anemia, asthenia, dehydration, lung infection, pleural effusion, pneumonia, and pneumonitis (n=2 each, 6%). Two DLTs, both pneumonitis, were reported (80 mg, grade 3; 120 mg, grade 5). Of 14 evaluable patients, 3 had PR (80 mg, n=2, both confirmed; 120 mg, single PR awaiting confirmation), 6 had SD (40 mg, n=3; 80 mg, n=2; 120 mg, n=1), and 5 had PD as best response (40 mg, n=3; 80 mg, n=1; 120 mg, n=1). All patients with PR had EGFR exon 20 insertions.
8eea62084ca7e541d918e823422bd82e Conclusion
TAK-788 exhibits antitumor activity in patients with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs. Phase 2 will begin after determination of the RP2D, with 4 molecularly defined cohorts in NSCLC. Updated data will be presented, including the recommended phase 2 dose (RP2D).
Baseline Characteristics 5 mg
(n=4)10 mg
(n=5)20 mg
(n=5)40 mg
(n=6)80 mg
(n=7)120 mg
(n=7)Total
(n=34)Mutation type,a %
Common EGFR mutations (exon 19 deletion / L8585R) 25 20 0 0 0 0 6 EGFR-T790M+ 0 0 0 0 14 0 3 EGFR exon 20 insertion 50 40 60 83 71 57 62 HER2 0 20 40 17 14 29 21 a One patient (20 mg) had both EGFR and HER2 mutations; 1 patient (80 mg) had EGFR exon 20 insertion + T790M.
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