Entry Detail
| General information | |
| Database: | DB00290 |
| Objective: | In thisphase Ib, doseescalation study, the oral irreversible ErbB family blocker afatinib (BIBW 2992) was combined with cisplatin (Cadila Healthcare Ltd, Ahmedabad, India) 50 or 75 mg/m(2)/paclitaxel (BristolMyers Squibb Pharmaceuticals Ltd, New York, USA) (Taxol)175 mg/m(2) (regimen A) or cisplatin 75100 mg/m(2)/5fluorouracil 7501000 mg/m(2) (regimen B) in patients with advanced solid tumors. |
| Authors: | Vermorken JB, et al |
| Title: | a phase Ib, openlabel study to assess the safety of continuous oral treatment with afatinib in combination with two chemotherapy regimens: cisplatin plus paclitaxel and cisplatin plus 5fluorouracil, in patients with advanced solid tumors. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 23293114 |
| Trial Design | |
| Clinical Trial Id: | NCT00716417 |
| Agent: | afatinib |
| Target: | Receptor proteintyrosine kinase erbB2 Epidermal growth factor receptor |
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | afatinib+two chemotherapy regimens: cisplatin plus paclitaxel and cisplatin plus 5fluorouracil |
| Study Type: | a phase Ib, openlabel study |
| Key Patients Feature: | patients were required to have cytologically or histologically confirmed nonresectable and/or metastatic cancer, preferably with SCCHN, esophagus, lung or cervix. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | afatinib+two chemotherapy regimens: cisplatin plus paclitaxel(arm A) and cisplatin plus 5fluorouracil(arm B) |
| Treatment Info: | Patients received once daily oral afatinib 20, 30, 40 or 50 mg in 21day cycles (3 + 3 design). |
| Primary End Point: | the MTD based on DLTs. |
| Secondary End Point: | Safety |
| Patients Number: | 47 |
| Trial Results | |
| DLT_MTD: | The MTD for afatinib in regimens A (n = 26) and B (n = 21) was determined as 20 mg and 30 mg following DLTs in five and four patients in cycle 1, respectively. |
| Objective Response Rate: | NA |
| Disease Control Rate: | Disease control was observed in 54% and 29% of patients in regimens A and B, respectively. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Most frequent adverse events (AEs, any grade) were diarrhea and nausea. |
| Conclusions: | The MTD of afatinib was 20 mg with cisplatinpaclitaxel and 30 mg with cisplatin5fluorouracil. Preemptive management of sideeffects is important to maintain adequate safety and tolerability. Both combinations showed antitumor activity across tumor types and lines of prior treatment. |