| General information |
| Database: | DB00768 |
| Objective: | Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to druginduced accumulation of acetylated proteins, including the heat shock protein 90. they prospectively studied the activity of vorinostat plus erlotinib in EGFRmutated non small cell lung cancer patients with progression to tyrosine kinase inhibitors. |
| Authors: | Reguart N, et al |
| Title: | Phase I/II trial of vorinostat (SAHA) and erlotinib for non small cell lung cancer (non small cell lung cancer) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression. |
| Journal: | Lung Cancer. |
| Year: | 2014 |
| PMID: | 24636848 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | Vorinostat and erlotinib
|
| Target: | Histone deacetylase 1
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | vorinostat (SAHA) + erlotinib |
| Study Type: | prospective, nonrandomized, multicenter, phase I/II trial |
| Key Patients Feature: | Patients with advanced non small cell lung cancer harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included |
| Biomarker: | EGFRmutated |
| Biomark Analysis: | the combination has no meaningful activity in EGFRmutated non small cell lung cancer patients after TKI progression |
| Control Group Info: | single arm |
| Treatment Info: | The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. Pretreatment plasma samples were required to assess T790M resistant mutation. |
| Primary End Point: | progression freesurvival rate at 12 weeks (PFSR12w) |
| Secondary End Point: | NA |
| Patients Number: | 33 |
| Trial Results |
| DLT_MTD: | No DLTs were observed at firstsecond level, rash being the only grade 3 AE reported. |
| Objective Response Rate: | NA |
| Disease Control Rate: | 28% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8 weeks (IC 95%: 7.438.45) |
| Median OS A vs. C: | 10.3 months (95% CI: 2.418.1) |
| Adverse Event(agent arm): | NA |
| Conclusions: | Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFRmutated non small cell lung cancer patients after TKI progression. |