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Dariusz Kowalski
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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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P1.01-79 - CheckMate 817: Safety of Flat-Dose Nivolumab Plus Weight-Based Ipilimumab for the First-line (1L) Treatment of Advanced NSCLC (ID 12004)
16:45 - 18:00 | Author(s): Dariusz Kowalski
- Abstract
Background
CheckMate 227 demonstrated significant, clinically meaningful progression-free survival benefit with 1L nivolumab 3 mg/kg every 2 weeks (Q2W) plus low-dose ipilimumab 1 mg/kg Q6W vs chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and tumor mutational burden (TMB) ≥10 mutations/megabase. The dose and schedule for this combination regimen were optimized for 1L NSCLC in CheckMate 012 and further validated in CheckMate 568 and CheckMate 227. Flat dosing of nivolumab (240 mg Q2W) may simplify treatment while providing comparable exposure, and was recently approved for previously treated NSCLC. CheckMate 817 (NCT02869789) is a multi-cohort, open-label phase 3b/4 study evaluating the safety and efficacy of flat-dose nivolumab plus weight-based low-dose ipilimumab in recurrent/metastatic NSCLC. We report safety results from Cohort A, which evaluated this regimen in the 1L setting; updated results will be presented.
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with ECOG PS ≤1 and previously untreated NSCLC were eligible, regardless of tumor programmed death ligand 1 (PD-L1) expression and TMB. Nivolumab 240 mg Q2W plus ipilimumab 1 mg/kg Q6W were administered for 2 years or until disease progression/unacceptable toxicity. The primary endpoint was safety assessed by the incidence of grade ≥3 select treatment-related adverse events (TRAEs; defined as AEs of potential immunologic causes).
4c3880bb027f159e801041b1021e88e8 Result
Enrollment occurred between October 2016 and August 2017, with 391 patients initiating treatment at 68 academic and community-based centers in Europe and North America. Median age was 65 years and 27.9% of patients had squamous histology. PD-L1 expression was evaluable in 91% of patients; of these, 50% had ≥1% tumor PD-L1 expression. At database lock (March 1, 2018), minimum follow-up was 5.4 months and 34.5% of patients remained on treatment. The median (range) number of nivolumab and ipilimumab doses received were 9 (1–28) and 3 (1–10), respectively. Any grade and grade 3–4 TRAEs occurred in 74.4% and 27.6% of patients, respectively; 14.1% of patients discontinued treatment due to TRAEs. Rates of any grade select TRAEs by category ranged from 1.3% (renal) to 28.4% (skin). The most common grade 3–4 select TRAEs by category were hepatic (4.6%), pulmonary (3.1%), and gastrointestinal (3.1%). Two treatment-related deaths were reported; one due to Guillain-Barré syndrome and one due to rhabdomyolysis leading to heart failure.
8eea62084ca7e541d918e823422bd82e Conclusion
The safety profile of flat-dose nivolumab plus low-dose ipilimumab was consistent with previous reports of weight-based nivolumab plus low-dose ipilimumab optimized for NSCLC. Toxicities were manageable with no new safety signals identified.
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P1.11 - Screening and Early Detection (Not CME Accredited Session) (ID 943)
- 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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P1.11-03 - MicroRNA with Ability to Reciprocal Regulation of Dicer and Drosha – Plasma Expression Status and Diagnostic Value in Non-Small Cell Lung Cancer (ID 12133)
16:45 - 18:00 | Author(s): Dariusz Kowalski
- Abstract
Background
Examination of microRNAs expression in plasma could be useful in screening and in early detection of non-small cell lung cancer (NSCLC). One of the most important enzymes in miRNA biogenesis are Dicer and Drosha. Disrupted expression of miRNA with ability to reciprocal regulation of Dicer and Drosha could participate in cancer development.
a9ded1e5ce5d75814730bb4caaf49419 Method
Plasma expression of miR-27-3p, miR-31, miR-182 and miR-195 were analysed in 138 Polish NSCLC patients (median age 65 years, 83 male and 55 female) and in 45 healthy people (median age 62 years, 28 male and 17 female). 57 (41.3%) NSCLC patient were in I-IIIA stage and 81 (58.7%) patients were in IIIB-IV stage. Relative expression of microRNAs between studied groups was compared using U Mann-Whitney test. For assessment of diagnostic accuracy (test sensitivity and specificity), the receiver operating curves (ROC) with area under curve (AUC) analysis were generated.
4c3880bb027f159e801041b1021e88e8 Result
We demonstrated that plasma levels of miR-27-3p, miR-31 and miR-182 were significantly higher (p<0.000001, p=0.00008, p=0.006 respectively) and miR-195 significantly lower (p=0.000002) in NSCLC patients in comparison with healthy donors. Moreover, patients with early stages (I-IIIA) of NSCLC showed significantly higher expression of miR-27a-3p (p<0.000001), miR-31 (p=0.0003) and miR-182 (p=0.000003) than healthy persons. Expression of miR-195 was significantly lower in patients with early stages (I-IIIA) of NSCLC than in healthy donors (p<0.000001). AUC for miR-27a was 0.95 (94% sensitivity and 81% specificity, p<0.00001), for miR-31 was 0.71 (73% sensitivity and 61% specificity, p=0.001), for miR-182 was 0.77 (70% sensitivity and 79% specificity, p<0.00001) and for miR-195 was 0.82 (74% sensitivity and 80% specificity, p=0.00001).
8eea62084ca7e541d918e823422bd82e Conclusion
Expression of miR-27a, miR-31, miR-182 and miR-195 could distinguish patients with NSCLC from healthy people. The examination of these microRNAs in plasma could be used in non-invasive lung cancer diagnosis. Deregulation of Dicer and Drosha expression by microRNAs could have oncogenic character.
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