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M. Gottfried
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Poster Display session (Friday) (ID 65)
- Event: ELCC 2018
- Type: Poster Display session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/13/2018, 12:30 - 13:00, Hall 1
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150P - Correlation between erlotinib-induced rash and efficacy in first-line therapy of patients with advanced non-small cell lung cancer (NSCLC) expressing epidermal growth factor receptor (EGFR)-mutation: A prospective, multi-center, open-label, single-arm, phase II study (ID 408)
12:30 - 13:00 | Presenting Author(s): M. Gottfried
- Abstract
Background:
Skin rash is the most common adverse event following erlotinib treatment, reported in about 75% of patients. Several retrospective analyses have suggested that erlotinib-induced skin rash may be associated with better therapeutic outcomes. This phase II TIME (Tarceva In Mutated EGFR patients) study assessed the relationship between erlotinib-induced rash and clinical efficacy in EGFR-mutated advanced NSCLC patients receiving erlotinib first line.
Methods:
Patients ≥18 years of age, with EGFR mutated stage IV or inoperable stage IIIB NSCLC, previously untreated with any systemic anti-neoplastic therapy for their advanced stage disease, were enrolled to receive oral erlotinib at an initial daily dose of 150 mg until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) according to rash grade.
Results:
Sixty patients (41 women, 19 men; median age, 70.7 years) were enrolled in 12 medical centers across Israel. Median PFS from the time of enrollment was 10.4 months (95% CI, 7.5–15.3). The incidence of grade 0, 1, 2, and 3 rash was 6.8%, 22.0%, 39.0% and 32.2%, respectively. Kaplan Meier survival analysis showed that patients with grade 2–3 rash had a statistically significant longer median PFS of 12.0 months (95% CI, 9.3–17.1) compared to patients with grade 0–1 rash who had a median PFS of 5.0 months (95% CI, 2.0–13.5), hazard ratio = 0.38, (95% CI, 0.20–0.71; p = 0.002). Similar results were observed in differentiation between exon 19 and exon 21 mutations.
Conclusions:
Albeit a relatively small sample of patients, the results of this prospective study strongly indicate that skin rash during treatment with erlotinib represents a significant predictive factor of efficacy in patients treated for advanced stage NSCLC. These results support previously published retrospective data. Patients might be reassured that rash severity indicates response to treatment. Moreover, an absence of rash as a response to treatment might be a negative prognostic factor in this group of patients.
Clinical trial identification:
ClinicalTrials.gov ID: NCT01174563
Legal entity responsible for the study:
Roche Pharmaceuticals (Israel) LTD
Funding:
Roche Pharmaceuticals (Israel) LTD
Disclosure:
M. Gottfried: Advisory Board and corporate sponsored research: Pfizer, BI, MSD, BMS, Roche, AZ, Abbvie. S. Keren Rosenberg: Advisory Boards: Roche, Pfizer, MSD, AZ, BI, Takeda Corporate-sponsored research: Roche. J. Dudnik: Advisory Boards: BI, Astra-Zeneca Corporate-sponsored studies: Roche, Astra-Zeneca, MSD, BMS, BI. M. Wollner: Corporate-sponsored research and consultations fees: Roche, MSD, BMS, AZ, BI, Pfizer Consultation fee: Takeda. J. Bar: Corporate-sponsored research: BI, AZ, Pfizer, Merck, Abbvie, Roche, AZ, MSD, BMS, BI Consulting fees: Roche, Pfizer, Takeda, Abbvie, VBL, BI, AZ, MSD, BMS. A. Onn: Advisory Board: Roche, BI, AZ, MSD. O. Frenkel: Employee of Roche Pharmaceuticals (Israel) Ltd. N. Maimon: Corporate-sponsored research: Roche, MSD, AZ, BI, Pfizer, Abbvie, BMS.
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9P - Mesenchymal stem cells’ microvesicles from primary and metastatic NSCLC niches differentially modulate lung cancer cells (ID 160)
12:30 - 13:00 | Author(s): M. Gottfried
- Abstract
Background:
Novel therapeutic approaches are urgently needed in lung cancer, particularly ones that address the malignant cells in their stroma microenvironment critical to drug resistance and disease relapse. The stroma constituents, mesenchymal stem cells (MSCs), interact with cancer cells by various methods including transfer of microvesicles (MVs) that vehicle protein, mRNA and microRNAs thereby altering recipient cells’ phenotype. Here, we examined the effect of MSCs’ MVs from primary (lung) and metastatic (bone marrow (BM)) niches on NSCLC cells with emphasis on translation initiation's (TI) role in the process.
Methods:
Lung and BM MSCs’ MVs were isolated and applied to NSCLC cell lines (H1299, H460). MVs uptake was confirmed and NSCLC cells were assayed for: viability (WST-1); cell count/death (trypan); proliferation (PCNA); migration (scratch); autophagy; TI status (factors, regulators, targets); MAPKs activation (immunoblotting).
Results:
We observed increased viability, proliferation and migration of Lung-MSCs’ MVs treated NSCLC cells whereas, BM-MSCs’ MVs treated cells showed reductions (50–90% and −40%, respectively p < 0.05). Correspondingly, Lung MSCs’ MVs elevated TI status whereas BM-MSCs’ MVs diminished it (60–120% and −30–70%, respectively p < 0.05). The opposite trend was also evident in MAPK activation and autophagy induction.
Conclusions:
Our observations not only depict a role for MSCs’ MVs in NSCLC phenotype but also display distinct differences between the primary and metastatic niches and may emphasize specific factors that shape disease progression. Further studies into the mechanism underlying the MVs-NSCLC cells’ contact and cargo transfer may promote the design of a therapeutic approach that will sabotage the dialogue between NSCLC cells and MSCs.
Clinical trial identification:
Legal entity responsible for the study:
Meir Medical Center
Funding:
Has not received any funding
Disclosure:
All authors have declared no conflicts of interest.
