| General information |
| Database: | DB00734 |
| Objective: | Optimum management strategies for patients with advanced non small cell lung cancer (non small cell lung cancer) with acquired resistance to EGFR tyrosinekinase inhibitors are undefined. they aimed to assess the efficacy and safety of continuing gefitinib combined with chemotherapy versus chemotherapy alone in patients with EGFRmutationpositive advanced non small cell lung cancer with acquired resistance to firstline gefitinib. |
| Authors: | Soria JC, et al |
| Title: | Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFRmutationpositive non small cell lung cancer after progression on firstline gefitinib (IMPRESS): a phase 3 randomised trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 26159065 |
| Trial Design |
| Clinical Trial Id: | NCT01544179 |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Gefitinib + chemotherapy |
| Study Type: | randomised, phase III, multicentre IMPRESS study |
| Key Patients Feature: | Eligible patients were aged at least 18 years with histologically confirmed, chemotherapynaive, stage IIIBIV EGFRmutationpositive advanced non small cell lung cancer with previous disease control with firstline gefitinib and recent disease progression (Response Evaluation Criteria in Solid Tumors version 1.1). |
| Biomarker: | EGFRmutationpositive |
| Biomark Analysis: | NA |
| Control Group Info: | Gefitinib plus chemotherapy versus placebo plus chemotherapy |
| Treatment Info: | Participants were randomly assigned (1:1) by central block randomisation to oral gefitinib 250 mg or placebo once daily in tablet form; randomisation did not include stratification factors. All patients also received the platinumbased doublet chemotherapy cisplatin 75 mg/m(2) plus pemetrexed 500 mg/m(2) on the first day of each cycle. After completion of a maximum of six chemotherapy cycles, patients continued their randomly assigned treatment until disease progression or another discontinuation criterion was met. All study investigators and participants were masked to treatment allocation. |
| Primary End Point: | progression free survival in the intentiontotreat population. Safety was assessed in patients who received at least one dose of study treatment. The study has completed enrolment, but patients are still in followup for overall survival. |
| Secondary End Point: | NA |
| Patients Number: | 265 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 32% in the gefitinib group and 34% in the placebo group |
| Disease Control Rate: | 84% in the gefitinib group and 79% in the placebo group |
| Median Time to Progression: | less than and equal to 10 months: 39% vs 44%; >10 months: 61% vs 56% |
| Median PFS A vs. C: | 5.4 months in both groups [95% CI 4.55.7 in the gefitinib group and 4.65.5 in the placebo group] |
| Median OS A vs. C: | 17.2 months (95% CI 15.6 to not reached) in the placebo group versus 14.8 months (10.4 to 19.0) in the gefitinib group. |
| Adverse Event(agent arm): | 37 (28%) of 132 patients in the gefitinib group and 28 (21%) of 132 patients in the placebo group reported serious adverse events. Adverse events leading to discontinuation were reported by ten (8%) of 132 patients in the gefitinib group and 13 (10%) of 132 in the placebo group. Adverse events of grade 3 or higher were reported in 59 (45%) of 132 patients in the gefitinib group and 55 (42%) of 132 in the placebo group. 13 adverse events resulted in death (five in the gefitinib group and eight in the placebo group), of which two deaths in the gefitinib group were deemed causally related to gefitinib and cisplatin plus pemetrexed treatment (pneumonia and dyspnoea), and one in the placebo group was considered causally related to cisplatin plus pemetrexed treatment (haemoptysis). Ten (8%) patients in the gefitinib group and 11 (8%) in the placebo group died during the 30day followup period after the last dose of study treatment. Grade 5 adverse events were experienced by five patients in the gefitinib group (one pneumonia, one dyspnoea, and three respiratory failure) and eight patients in the placebo group (one pneumonia, one cerebral infarction, one cerebrovascular accident, one cardiac failure, one dyspnoea, one haemoptysis, one gastric perforation, and one multiorgan failure) |
| Conclusions: | Continuation of gefitinib after radiological disease progression on firstline gefitinib did not prolong progression free survival in patients who received platinumbased doublet chemotherapy as subsequent line of treatment. Platinumbased doublet chemotherapy remains the standard of care in this setting. |