| General information |
| Database: | DB00329 |
| Objective: | This randomizedphase II trial was designed to select a cetuximab plus chemotherapy regimen forphase III evaluation. |
| Authors: | Herbst RS, et al |
| Title: | Phase II selection design trial of concurrent chemotherapy and cetuximab versus chemotherapy followed by cetuximab in advancedstage non small cell lung cancer: Souththeyst Oncology Group study S0342. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 20921467 |
| Trial Design |
| Clinical Trial Id: | NCT00085501 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| 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: | paclitaxel+carboplatin+maintenance cetuximab |
| Study Type: | Phase II Selection Design Trial |
| Key Patients Feature: | Eligible patients were 18 years old, with histologically or cytologicallyproven non small cell lung cancer, a Zubrod performance status of 0 to 1, measurable disease asdefined by the Response Evaluation Criteria in Solid Tumors (RECIST), andadequate bone marrow, liver, and renal function.28 Patients had newly diagnosed selected stage IIIB (T4 lesion as a result of malignant pleural effusion) orstage IV disease or had recurrent disease after previous surgery and/or irradiation. |
| Biomarker: | KRAS Mutation |
| Biomark Analysis: | KRAS mutation status was not significantly associated withany efficacy parameter. |
| Control Group Info: | A:concurrent arm, concurrent chemotherapy and cetuxima B: sequential arm, chemotherapy followed by cetuximab |
| Treatment Info: | patients were randomly assigned to receive paclitaxel (225 mg/m(2)) and carboplatin (area under the curve, 6) every 3 weeks plus concurrent cetuximab (400 mg/m(2) loading dose followed by 250 mg/m(2) weekly) for four cycles followed by maintenance cetuximab or sequential paclitaxelcarboplatin for four cycles followed by cetuximab. |
| Primary End Point: | to select a regimen for further testing against standard treatment (chemotherapy alone). |
| Secondary End Point: | NA |
| Patients Number: | 242 |
| Trial Results |
| DLT_MTD: | Cetuximabrelated grade 3 or 4 toxicities were uncommonand similar in both arms. Grade 3 or 4 rash occurred in13%of patientson the concurrent arm and 7% on the sequential arm |
| Objective Response Rate: | the median overall survival was 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P .57); 1year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35%to 53%), respectively. Response rates and progression free survival times were similar in both arms, as was grade 3 rash, whereas sensory neuropathy was higher in the concurrent arm |
| Disease Control Rate: | paclitaxel/ carboplatin plus cetuximab and paclitaxel/carboplatin followed by cetuximab arms: 67%and70% (P=.66), respectively. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | patients with adenocarcinoma treated on either arm was 4.9 months compared with 3.9 months for all other histologies (HR = 0.60, P <0 .001). Median PFS was 4.3 months (95% CI, 3.7 to 4.7 months) for patients on the concurrent arm and 4.4 months (95% CI, 4.0 to 5.3 months) for patients on the sequential arm. |
| Median OS A vs. C: | 10.9 months (95% CI, 9.2 to 13.0 months) for patients receiving concurrent therapy and 10.7 months (95% CI, 8.5 to 12.8 months) for patients receiving sequential therapy (P= .57); 1year survival rates were 45% (95% CI, 36% to 54%) and 44% (95% CI, 35% to 53%), respectively. |
| Adverse Event(agent arm): | Grade3or4neutropeniaoccurred in44% of patients in the concurrent arm and 38% in the sequential arm. Febrile neutropenia was reported in 5% ofpatients in the concurrent arm and less than 1% in the sequential arm. The only significant toxicity difference was a higher rate ofgrade 3 or 4 sensoryneuropathy in the concurrent arm (15% v 5% in the sequential arm; P = .02). however, overall grade 3 or 4 toxicities were significantly increased in patients receiving the concurrent regimen (82%) compared with patients treated with the sequential regimen (63%; P = .002). Two treatmentrelated deaths were reported, one in each study arm. One patient in the concurrent arm died from infection and acute respiratory distress syndrome, and one patient in the sequential arm died from dehydration. |
| Conclusions: | Although both regimens met the efficacy criterion for continued evaluation, the concurrent regimen of paclitaxelcarboplatin plus cetuximab was chosen. |