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M.E. Olmedo
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MA 01 - SCLC: Research Perspectives (ID 650)
- Event: WCLC 2017
- Type: Mini Oral
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:John V Heymach, Eun Kyung Cho
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 503
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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)
11:30 - 11:35 | Author(s): M.E. Olmedo
- Abstract
- Presentation
Background:
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).
Method:
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.
Result:
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%).
Conclusion:
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.
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MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
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MA 07.03 - Incidence, Predictors and Prognostic Significance of Thromboembolic Events in Patients with Advanced Alk-Rearranged NSCLCs (ID 9532)
15:55 - 16:00 | Author(s): M.E. Olmedo
- Abstract
- Presentation
Background:
The incidence of venous thromboembolic events all along the course of the disease in advanced-stage lung adenocarcinomas is approximately 15 %. It is plausible that the different molecular subtypes might influence on the risk of thrombosis. Based on our clinical observation, and supported by limited data from isolated small series, patients bearing ALK rearranged tumors could be at a particularly high-risk of thromboembolic disease.
Method:
We included consecutive patients diagnosed with advanced-stage ALK fusion positive non-small cell lung cancers (NSCLC) between January 2012 and December 2016. Clinical data were contributed by 29 Medical Centers from Spain and one large Academic Cancer Center from Portugal. Investigators at each institution retrospectively reviewed patients’ medical records. A thromboembolic event was defined as any venous or arterial thromboembolism, or both, at any site, documented by appropriate imaging studies, that occurred at the time or after advanced-stage cancer diagnosis.
Result:
A total of 241 ALK-rearranged NSCLCs were included in our study. Half of the patients were never smokers (52 %), and most had stage IV pulmonary adenocarcinomas (n=204, 85%). Baseline brain and liver metastasis were detected in 22 % and 25 % of the patients respectively. Seventy-three patients (30 %) developed thromboembolic disease. In 54 patients (74 %) thromboembolic complications occurred within the first 6 months from diagnosis. In the multivariate competing-risk regression analysis, the presence of baseline liver metastases (HR of 1.85, CI 95 % 1.09-3.15; p = 0.021) and baseline leukocyte counts > 11.0000 cells/mm3 (HR of 2.34, CI 95 % 1.43-3.82; p = 0.001) were independent predictors of thromboembolic disease. Remarkably, 50 % of the patients with either liver metastases or leukocytosis at diagnosis developed thromboembolic disease. Patients experiencing thromboembolic events had shorter median overall survival (OS) (20 months) than patients without thrombosis (36 months) (p = 0.035). In the multivariate Cox Model, thromboembolic disease remained associated with worse OS (HR of 1.70, CI 95 % 1.10-2.62; p = 0.016) when considered as a time-varying covariate. The presence of baseline thromboembolic disease (n = 24) was associated with a numerical non-significant increased risk of death (HR 1.67, CI 95 % 0.96-2.91; p = 0.068).
Conclusion:
Venous and/or arterial thromboembolic complications occur in a high proportion of patients with advanced-stage ALK fusion positive NSCLCs, particularly in the presence of baseline liver metastasis or leukocytosis. The development of thromboembolic disease is associated with a lower OS in these patients.
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