| General information |
| Database: | DB00828 |
| Objective: | The phosphotidylinositol3 kinase/serinethreonine kinase (AKT)/mammalian target of rapamycin signaling pathway is frequently altered in non small cell lung cancer (non small cell lung cancer). PX866 is an oral, irreversible, panisoform inhibitor of phosphotidylinositol3 kinase. Preclinical models revealed synergy with docetaxel and a phase 1 trial demonstrated tolerability of this combination. This randomizedphase 2 study evaluated PX866 combined with docetaxel in patients with advanced, refractory non small cell lung cancer. |
| Authors: | Levy B, et al |
| Title: | A randomized, phase 2 trial of Docetaxel with or without PX866, an irreversible oral phosphatidylinositol 3kinase inhibitor, in patients with relapsed or metastatic non small cell lung cancer. |
| Journal: | J Thorac Oncol. |
| Year: | 2014 |
| PMID: | 24926548 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | PX866
|
| Target: | PI3K gamma
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Docetaxel with PX866 |
| Study Type: | A randomized, phase II trial |
| Key Patients Feature: | Patients with locally advanced, recurrent, or metastatic non small cell lung cancer who had received at least one and no more than two prior systemic treatment regimens |
| Biomarker: | PIK3CA mutations or PTEN loss |
| Biomark Analysis: | PIK3CA mutations or PTEN loss were infrequently observed. |
| Control Group Info: | Docetaxel with or without PX866 |
| Treatment Info: | patients were randomized (1:1) to a combination of docetaxel (75 mg/m intravenous every 21 days) with or without PX866 (8 mg orally daily; arms A and B, respectively). |
| Primary End Point: | progression free survival (PFS). |
| Secondary End Point: | objective response rate, overall survival (OS), toxicity, and correlation of biomarker analyses with efficacy outcomes. |
| Patients Number: | 95 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 6% and 0% in arms A and B, respectively (p = 0.4). |
| Disease Control Rate: | 35% in arm A; 53% in arm B |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 2 months in arm A and 2.9 months in arm B (p = 0.65) |
| Median OS A vs. C: | A vs B: 7.0 versus 9.2 months; p = 0.9 |
| Adverse Event(agent arm): | There seemed to be more allgrade toxicity in arm A including diarrhea (76% versus 25%), nausea (56% versus 30%), vomiting (42% versus 21%), anorexia (40% versus 18%), and fatigue (62% versus 43%). however, there were few grade 3 or higher AEs in either arms excluding neutropenia (9% and 25% in arms A and B, respectively). No patients in arm A withdrew due to AEs, whereas five patients in arm B were taken off study because of toxicity. |
| Conclusions: | The addition of PX866 to docetaxel did not improve PFS, response rate, or OS in patients with advanced, refractory non small cell lung cancer without molecular preselection. |