Holly Tuttle

Phase II Trial of Cetuximab With or Without Paclitaxel in Patients With Advanced Urothelial Tract Carcinoma

PURPOSE The benefit of salvage chemotherapy is modest in metastatic urothelial cancer. We conducted a randomized, noncomparative phase II study to measure the efficacy of cetuximab with or without paclitaxel in patients with previously treated urothelial cancer. PATIENTS AND METHODS Patients with metastatic urothelial cancer who received one line of chemotherapy in the perioperative or metastatic setting were randomly assigned to 4-week cycles of cetuximab 250 mg/m(2) with or without paclitaxel 80 mg/m(2) per week. We used early progression as an indicator of futility. Either arm would close if seven of the initial 15 patients in that arm progressed at the first disease evaluation at 8 weeks. RESULTS We enrolled 39 evaluable patients. The single-agent cetuximab arm closed after nine of the first 11 patients progressed by 8 weeks. The combination arm completed the full accrual of 28 patients, of whom 22 patients (78.5%) had visceral disease. Twelve of 28 patients had progression-free survival greater than 16 weeks. The overall response rate was 25% (95% CI, 11% to 45%; three complete responses and four partial responses). The median progression-free survival was 16.4 weeks (95% CI, 12 to 25.1 weeks), and the median overall survival was 42 weeks (95% CI, 30.4 to 78 weeks). Treatment-related grade 3 and 4 adverse events that occurred in at least two patients were rash (six cases), fatigue (five cases), and low magnesium (three cases). CONCLUSION Although it had limited activity as a single agent, cetuximab appears to augment the antitumor activity of paclitaxel in previously treated urothelial cancers. The cetuximab and paclitaxel combination merits additional study to establish its role in the treatment of urothelial cancers.

Phase II Study of Paclitaxel, Carboplatin, and Cetuximab as First Line Treatment, for Patients with Advanced Non-small Cell Lung Cancer (NSCLC): Results of OPN-017

Background: Cetuximab has demonstrated synergy with taxanes in preclinical models; as well as single agent activity. We assessed the activity of cetuximab with carboplatin and paclitaxel given on a 4-week schedule, in advanced, chemo-naive non-small cell lung cancer. Patients and Methods: This phase II, single arm, multi-institution study featured standard dosage of cetuximab 400 mg/m2 day 1, then 250 mg/m2 with paclitaxel (100 mg/m2/wk, for 3 weeks), and carboplatin (area under curve = 6) day 1 of each 28 day cycle. After 4 to 6 cycles, in the absence of disease progression or excess toxicity, cetuximab was continued weekly. Primary end point was response rate. Results: Fifty-three patients (median age 63, 51% male) participated. Response rate was 57% (3 complete response and 27 partial response). At a median follow-up of 12.5 months, the estimated overall survival is 13.8 months (95% CI: 9.08–16.02) with an event-free survival rate of 5.53 months (95% CI: 4.77–7.99), 18.9% remain free from progression at 1 year. Improved survival was associated with female gender, absence of prior radiation, PS 0 and epidermal growth factor receptor expression. Toxicities included rash (28% grade 3), nail changes (3.7% grade 3), hypomagnesemia (7.5% grade 3 and 3.7% grade 4), and neutropenia (25% grade 3 and 13% grade 4) in addition to other typical side effects anticipated with paclitaxel/carboplatin. There were no grade 5 toxicities. Conclusion: Combination of cetuximab/paclitaxel/carboplatin in non-small cell lung cancer was well tolerated and clinically active with manageable toxicities. This unique schedule, integrating weekly paclitaxel and cetuximab has not yet been tested in a randomized trial.

Promising Survival in Patients with Recurrent Non-small Cell Lung Cancer Treated with Docetaxel and Gemcitabine in Combination as Second-Line Therapy

Introduction: Lung cancer is the leading cause of cancer death in men and women, and current second-line chemotherapy regimens yield relatively poor response and survival rates. Hypothesis: We hypothesized that the combination of weekly docetaxel (D) and gemcitabine (G) would show activity in the second-line setting. We therefore conducted a phase II trial evaluating this regimen in patients with relapsed or progressive non-small cell lung cancer (NSCLC) after first-line platinum-based therapy. Methods: Patients with recurrent NSCLC, adequate physiologic indices, and exposure to one prior platinum-based regimen were eligible. Docetaxel 40 mg/m2 intravenous (IV) and gemcitabine (G) 800 mg/m2 IV weekly were administered on day 1 and 8 every 21 days. In the absence of dose-limiting toxicity, G was escalated on an intrapatient basis to 1 g/m2/wk. The primary endpoint was response rate (RR); event-free (EFS) and overall survival were secondary endpoints. Results: Thirty-five patients (median age 61 years; 20 [57%] male) were accrued. Most (88%) had previously received carboplatin/paclitaxel, 31.4% in combination with a third investigational agent, more than half (57.1%) had prior radiation. The median number of cycles was four. RR was 23%. Median EFS was 5.7 months and median overall survival was 12.5 months. Patients who had their cancer diagnosed more than or equal to 12 months before entering the trial had superior EFS (13.7 months versus 4.8 months). Toxicity was acceptable. There were no treatment-related deaths. Conclusions: A nonplatinum doublet with GD is feasible and effective in the treatment of recurrent, platinum-exposed NSCLC patients. RR and survival are promising.

Novel early stopping rule uses early progression rather than lack of response as rapid assessment for futility.

TPS227 Background: Median survival for patients (pts) with metastatic (met) urothelial cancer (UroCa) is approximately 15 months due to the lack of active salvage agents. With the exception of gemc...