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E. Smit
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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)
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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. Smit
- 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
