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M.P. Lopez Criado
MA 01 - SCLC: Research Perspectives (ID 650)
- Event: WCLC 2017
- Type: Mini Oral
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
MA 01.05 - Activity and Safety of the Combination of PM01183 and Doxorubicin in Relapsed SCLC. Final Results of a Phase Ib Trial (ID 9249)
11:00 - 12:30 | Author(s): M.P. Lopez Criado
Lurbinectedin (PM01183) is a new anticancer drug that binds to DNA, inhibits transactivated transcription and modulates tumor microenvironment. Preclinical evidence of synergism was observed for PM01183 in combination with doxorubicin (DOX).
Multicenter, phase I clinical trial to determine the recommended dose (RD) of the combination of PM01183 and DOX. An expansion cohort was recruited after finding striking activity in second-line small cell lung cancer (SCLC) patients. Due to hematological toxicity, the trial was amended to use a lower DOX dose and thus improve safety of the combination in selected indications. SCLC patients <75 years with ECOG performance status (PS) 0-1 and pretreated with no more than one chemotherapy line were included. Stable brain metastases were allowed. DOX was interrupted after 10 cycles and PM01183 could be continued as single-agent. Primary G-CSF prophylaxis was not mandatory.
48 patients were treated: 21 in Cohort A (PM01183 3-5 mg flat dose [FD] Day (D)1 + DOX 50 mg/m2 D1 every 21 days [q21d]), and 27 in Cohort B (PM01183 2 mg/m2 D1 + DOX 40 mg/m2 D1 q21d). Males: 74%; median age: 64 (48-77) years, ECOG 0-1: 37%-63%; known central nervous system (CNS) involvement: 10%; bulky disease (>50 mm): 67%. 85% responded to first line, including 4% with complete response (CR). Median chemotherapy free interval (CTFI): 3.4 months. Refractory (CTFI<30 days) 23%; resistant (CTFI 30-90 days) 34%; sensitive (CTFI>90 days) 43%. RD: PM01183 4 mg FD (or 2 mg/m2) + DOX 50 mg/m2 D1 q21d. Confirmed ORR: 50% (95CI: 35-65%) with 6% CR in both cohorts; ORR=69% (95CI: 49-85%) with 10% CR in sensitive patients. Cohort A: ORR=67% (95%CI: 43-85%) with 10% CR; ORR=92% (95%CI: 62-100%) in sensitive patients. Cohort B: ORR=37% (95%CI: 19-58%) with 4% CR; ORR=53% (95%CI: 28-77%) in sensitive patients. Median PFS (mPFS) 4.6 months (95%CI: 3.1-5.8), with mPFS 1.5 months (95%CI: 1.2-3.8) in resistant patients and 5.8 months (95%CI: 3.6-7.9) in sensitive patients. In both cohorts, grade 4 neutropenia/anemia/thrombocytopenia appeared in 73%/4%/15% of patients and febrile neutropenia in 21% (11% at RD). Non-hematological toxicity was mainly fatigue (G3=14%) and nausea (G3=5%).
PM01183/DOX combination showed remarkable activity as second line in SCLC, especially in patients with CTFI>90 days, regardless of dose. Activity is higher than reported for CAV or topotecan in this setting. Reversible myelosuppression was the most frequent and expected side effect. A phase III trial with this combination in relapsed SCLC is ongoing.
P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
P2.01-022 - Nintedanib/Docetaxel Efficacy in Advanced Lung Adenocarcinoma Treated with 1L Chemotherapy/2L Immunotherapy in Nintedanib NPU (ID 8639)
09:00 - 16:00 | Author(s): M.P. Lopez Criado
Both antiangiogenic agents (nintedanib and ramucirumab) in combination with docetaxel and monotherapy with anti-PD-1/ PD-L1 immunotherapy have demonstrated efficacy as second-line (2L) treatment of patients with stage IV lung adenocarcinoma. However, selection of optimal candidates and the most appropriate therapeutic sequence is under discussion. Herein, we report on the efficacy of the nintedanib/docetaxel combination following first-line (1L) platinum-based chemotherapy and subsequent immunotherapy in a real-world setting.
From May 2014 to December 2015, 390 patients in 108 Spanish centers enrolled in the nintedanib Named Patient Use (NPU) program. NPU inclusion criteria were advanced lung adenocarcinoma with progressive disease following at least one line of platinum-based doublet chemotherapy. We retrospectively assessed patients that received immunotherapy (available through clinical trials or the nivolumab NPU program) prior to nintedanib/docetaxel. The aim of this analysis was to evaluate the efficacy of the nintedanib/docetaxel combination in this new clinical setting.
Eleven patients met the inclusion criteria for this analysis: 64% were men; median age of 67 years (range, 44–74); ECOG performance status 0-1 in 100% of patients; median number of treatment lines before inclusion in the nintedanib NPU program was 2 (range, 2-3); PD-L1 expression was positive (unknown cut-off) in 6 patients and was not determined in 5 patients. Median progression-free survival (PFS) of first-line platinum-based chemotherapy was 3.3 months (range 1.4-9.4): 9 patients (82%) had progressed <6 months since start of first-line treatment and 4 patients (36%) had progressed <3 months. Second-line immunotherapy was pembrolizumab (36.5%), atezolizumab (36.5%) and nivolumab (27%). Median PFS of second-line immunotherapy was 2.3 months (range, 0.7-11). The overall response rate (ORR) to second-line immunotherapy was 18% with a disease-control rate (DCR) of 45%. The median number of treatment cycles of nintedanib/docetaxel was 4.5 (range, 2-22). Median PFS of nintedanib/docetaxel post first-line chemotherapy and second-line immunotherapy was 3.2 months (range, 1.4-14.6). Best response was partial response in 4 patients (36%), stable disease in 5 patients (46%), and progressive disease in 2 patients (18%), for an ORR of 36% and a DCR of 82%.
Our experience in the Spanish nintedanib NPU program in patients with adenocarcinoma NSCLC pretreated with platinum-based doublet chemotherapy and immunotherapy suggests an encouraging ORR and DCR of nintedanib/docetaxel as compared with clinical trial results. These results reinforce the importance of an optimal therapeutic sequence for managing advanced lung adenocarcinoma: 1) Nintedanib/docetaxel should be the recommended second-line treatment in early progressors and 2) Possible chemosensitization effect by immunotherapy.