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F. Badin
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MINI 37 - SCLC Therapy (ID 165)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:D. Ettinger, G.R. Simon
- Coordinates: 9/09/2015, 18:30 - 20:00, 605+607
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MINI37.05 - Carfilzomib, Carboplatin and Etoposide for Previously Untreated Extensive-Stage Small Cell Lung Cancer: Initial Results from a Phase 1b/2 Study (ID 3008)
18:55 - 19:00 | Author(s): F. Badin
- Abstract
- Presentation
Background:
Proteasome inhibitors synergize with topoisomerase inhibitors (eg, etoposide), which are frequently used to treat extensive-stage small cell lung cancer (ES-SCLC; Takigawa et al. Anticancer Res 2006;26:1869–76). Results from study PX‑171-007 (NCT00531284) suggest that carfilzomib has activity in relapsed SCLC (Papadopoulos et al. Cancer Chemother Pharmacol 2013;72:861–8), and clinical experience in myeloma suggests that carfilzomib may be added to other agents with limited additive toxicity. Preliminary results are presented from the phase 1b portion of the CFZ004 trial (NCT01987232) intended to determine the maximum tolerated dose (MTD) and safety of carfilzomib with carboplatin and etoposide in patients with previously untreated ES-SCLC.
Methods:
Patients received carfilzomib (30-minute intravenous infusion) on days 2, 3, 9, and 10 (20 mg/m[2] [days 2 and 3 of cycle 1]; 20–56 mg/m[2] thereafter) and fixed doses of carboplatin (target area under the concentration-time curve: 5 mg/mL/min) on day 1 and etoposide (100 mg/m[2]) on days 1, 2, and 3 of a 21‑day cycle for up to 6 cycles. Assessment of dose‑limiting toxicities (DLTs) in cycle 1 was used to determine dose escalation up to the MTD or recommended phase 2 dose. Disease response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Patients achieving ≥stable disease (SD) after 6 cycles could receive single-agent carfilzomib until disease progression or unacceptable toxicity.
Results:
As of March 31, 2015, 17 patients (median age: 59.0 years) had been treated in the phase 1b portion in 5 dosing cohorts; enrollment in the 56-mg/m[2] cohort is ongoing. Patients initiated a median of 6 cycles of carfilzomib; the median treatment duration was 16.3 weeks. One patient (56-mg/m[2] cohort) experienced a DLT. There were no on-study deaths. Two patients discontinued carfilzomib due to an adverse event (AE; metastatic pain: n=1; decreased neutrophil count: n=1). All-grade AEs were generally consistent with the profiles of the agents under study. Thirteen patients (76.5%) had a grade ≥3 AE; the most common (≥3 patients) were anemia (n=4), neutropenia (n=4), decreased neutrophil count (n=4), and leukopenia (n=3). The preliminary overall response rate (≥partial response) in 14 response-evaluable patients was 57.1%, with 1 complete response (Table 1). All response-evaluable patients achieved ≥SD.
Conclusion:
The MTD of carfilzomib with carboplatin and etoposide has not been reached. Patients are showing encouraging responses to treatment, with AEs generally consistent with the profiles of the agents under study. Response data, currently immature, will be updated at the meeting. Table 1. Phase 1b Best Overall Responses per Investigators
[a]Per RECIST, v1.1.Cohort 1 2 3 4 5 Total CFZ, mg/m[2] 20/20 (n=5) 20/27 (n=3) 20/36 (n=3) 20/45 (n=3) 20/56 (n=3) (N=17) Best overall response, n (%)[a] CR 0 1 (33.3) 0 0 0 1 (5.9) PR 2 (40.0) 2 (66.7) 3 (100.0) 0 0 7 (41.2) SD 3 (60.0) 0 0 2 (66.7) 1 (33.3) 6 (35.3) Not evaluable 0 0 0 1 (33.3) 2 (66.7) 3 (17.6) Overall response rate (CR+PR), n (%) All patients 2 (40.0) 3 (100.0) 3 (100.0) 0 0 8 (47.1) Response-evaluable patients 2 (40.0) 3 (100.0) 3 (100.0) 0 0 8 (57.1)
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