Outcomes Associated with Brain Metastases in a Three-Arm Phase III Trial of Gemcitabine-Containing Regimens Versus Paclitaxel Plus Carboplatin for Advanced Non-small Cell Lung Cancer

BACKGROUND: Brain metastases (BMs) are a common complication of non-small cell lung cancer (NSCLC). Because of historical data indicating a poor prognosis for patients with BM, few randomized phase III studies of advanced NSCLC have included patients with BM at presentation. Because the potential benefits of systemic therapy in patients with BM are uncertain, we analyzed data from a recent phase III study. METHODS: One thousand one hundred thirty-five chemonaïve patients with stage IIIB/IV NSCLC were randomized to receive gemcitabine/carboplatin, gemcitabine/paclitaxel, or paclitaxel/carboplatin. Stratification was based on presence or absence of BM, stage, and baseline weight loss. Patients with BM were required to be clinically stable after treatment with radiotherapy or surgery before entry. Results were retrospectively analyzed by presence or absence of BM at study entry. RESULTS: Rate of BM was 17.1% overall. The response rate was 28.9% for patients with BM (n = 194) versus 29.1% without BM (n = 941). Time to progression was 4.3 months with BM and 4.6 months without BM (p = 0.03). Median survival was 7.7 months (95% confidence interval: 6.7-9.3) among patients with BM (n = 194) and 8.6 months (95% confidence interval: 7.9-9.5) for patients without BM (n = 941), p = 0.09. Rates of hematologic adverse events were not different among patients with and without BM. CONCLUSIONS: There were no significant differences in response, survival, or hematologic toxicity for patients with or without BM; however, patients with BM had a small but significantly shorter time to progression. Nonprogressing patients with treated BM are appropriate candidates for systemic therapy and entry into clinical trials

Neoadjuvant Chemotherapy with Gemcitabine-Containing Regimens in Patients with Early-Stage Non-small Cell Lung Cancer

BACKGROUND: Surgical resection alone remains suboptimal for patients with early-stage (I or II) non-small cell lung cancer. Two similar randomized phase II trials were conducted to define an active preoperative regimen in this disease state. METHODS: In the first study, patients were randomized to receive gemcitabine 1000 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1 (GC) or gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1 (GCb). In the second trial, patients received the same regimen of GCb or gemcitabine 1000 mg/m2 on days 1 and 8 plus paclitaxel 200 mg/m2 on day 1 (GP). Cycles were repeated every 21 days for three cycles. The primary end point was pathologic complete response (pCR) rate. RESULTS: Eighty-seven eligible patients were randomized (GC n = 12, GP n = 35, and GCb n = 40), and 71 (82%) underwent surgery after chemotherapy. The confirmed pCR rate was 2.3% (2 of 87, 95% confidence interval 0.3-8.1). Clinical response rate was 28.7%, complete resection rate was 91.5% (65 of 71 patients), and perioperative mortality rate was 2.8%. As of October 2006, median survival for all patients was 45 months (65.5% censored), with 87.2% alive at 1 year and 69.8% alive at 2 years. DISCUSSION: Neoadjuvant chemotherapy with gemcitabine was feasible and well tolerated, and outcomes were similar to other reports of this treatment strategy. However, no regimen achieved the predefined pCR rate that would be sufficient to warrant further evaluation in the phase III setting. This trial design provides an efficient way of providing a rationale for choosing or rejecting regimens of potential value

Phase 1/2 Dose Escalating Study of Twice-Monthly Pemetrexed and Gemcitabine in Patients with Advanced Cancer and Non-small Cell Lung Cancer

IntroductionPemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study.MethodsThe phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B12, and steroid prophylaxis.ResultsMaximum tolerated dose was gemcitabine 1500 mg/m2, followed by pemetrexed 500 mg/m2. Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship = 20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%).ConclusionsTwice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients

A Comparison of White and African American Outcomes from a Three-Arm, Randomized, Phase III Multicenter Trial of Advanced or Metastatic Non-small Cell Lung Cancer

PURPOSE: To investigate the effect of race on the efficacy and safety of standard chemotherapy doublet regimens in African American patients, we conducted a subgroup analysis of a phase III randomized trial. PATIENTS AND METHODS: Chemonaïve patients with a performance status of 0 or 1 and stage IIIB or IV non-small cell lung cancer were randomized to arm A: gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1; arm B: the same schedule of gemcitabine plus paclitaxel 200 mg/m2 on day 1; or arm C: paclitaxel 225 mg/m2 on day 1 plus carboplatin area under the curve 6.0 on day 1. Cycles were repeated every 21 days up to 6. A site selection tool identified institutions with potential to recruit a minority population. Outcome and toxicity data of white and African American patients were compared. RESULTS: Of 1135 total patients, 972 were white (85.6%) and 138 were African American (12.2%). Median survival was 8.3 months for white patients (95% confidence interval [CI]: 7.7-9.3) and 9.1 months for African American patients (95% CI: 8.2-11.1). Response rates were 29.1 and 29.0%, respectively. Rates of grade 3 or 4 toxicities were comparable. Among African Americans, median survival was 7.2 months (95% CI: 5.1-10.1) for gemcitabine-carboplatin (n = 47), 10.5 months (95% CI: 7.1-15.4) for gemcitabine-paclitaxel (n = 42), and 10.2 months (95% CI: 8.5-13.2) for paclitaxel-carboplatin (n = 49). CONCLUSION: Whites and African Americans had similar outcomes, although there was some variability in survival among African Americans across the three treatment groups

Evaluation of the Patterrns and Risks of Erythropoietin Stimulating Agents in Head and Neck Cancers

Background: Although head and neck cancer (HNC) is the sixth most common cancer type by incidence globally, few studies have focused on real world treatment patterns of this disease. A large, randomized study of erythropoietin stimulating agents (ESAs) produced worsened outcomes in patients with HNC. Real-world data on the treatment patterns HNC, and the use and outcomes of ESAs in this population is currently lacking. Methods: SEER Medicare was used to evaluate patients aged ≥65 years with a first diagnosis of HNC between 2002 and 2007. Logistic regression was used to evaluate predictors of treatment. An interrupted time series was used to estimate the changes in ESA use among patients receiving chemotherapy over time. Propensity weighted models predicted survival, thromboembolism (TEE), and disease recurrence outcomes associated with ESA exposure. Results: Characteristics associated with no treatment for HNC included being unmarried (adjusted OR=2.00, 95% CI: 1.75, 2.27) or African American (adjusted OR=1.65, 95% CI: 1.37, 1.98). ESA use was 50.0% among patients receiving chemotherapy and 3.1% among patients not receiving chemotherapy. ESA use was 50.0% among patients receiving chemotherapy and 3.1% among patients not receiving chemotherapy. Combination regimens such as cetuximab+taxane+platinum (63.8%) and taxane+platinum (56.0%) were associated with the highest rates of ESA use, while single-agent cetuximab was associated with the lowest rate of ESA use (22.3%). Use of ESAs significantly declined from 40.3% of patients receiving chemotherapy in January 2007 to 16.7% in August 2007. Patients receiving an ESA were more likely to have a TEE (adjusted HR=1.19 [95% CI: 1.31, 1.81), experience disease recurrence (adjusted HR=1.09 [95% CI: 1.00, 1.16]), or die (adjusted HR=1.17 [95% CI: 1.06, 1.30]). Discussion: Disparities in the diagnosis and treatment of patients with HNC were present, despite the uniform insurance status of patients in the database. Significant declines in ESA occurred following FDA action in January 2007. ESA use increased among HNC patients in the immediate aftermath of previous disclosure of negative trial data (June 2003). ESAs may be associated with modestly worsened outcomes in HNC

Characteristics, treatment patterns, and outcomes in patients with high-risk locally advanced cervical cancer

Objective: To characterize the real-world treatment patterns and outcomes of patients with high-risk locally advanced cervical cancer (HR-LACC). Methods: This retrospective study identified and randomly selected adults diagnosed between 2010 and 2018 from the ConcertAI Oncology Dataset. For patients initially treated with concurrent chemoradiotherapy (CCRT), we estimated real-world progression-free survival (rwPFS) among those with persistent disease, real-world time on CCRT, and recurrence-free survival (rwRFS) using Kaplan-Meier methods. Results: The cohort included 300 patients. Median age at diagnosis was 51 years. 53.7 % were White and 30.0 % were Black; 52.0 % were premenopausal; 89.3 % had squamous cell histology; 75.3 % had stage III disease, and 92.7 % had no evidence of performance status impairment. Initial treatment included CCRT (N = 229), surgery (N = 28), antineoplastics only (N = 11), and radiation only (N = 5). Twenty-seven patients were untreated. Baseline characteristics for the CCRT-first patients were similar to the overall cohort; their median real-world time on treatment was 1.6 months; 78.2 % received cisplatin for a median of 1.2 months; 28.4 % received antineoplastics after CCRT, and 11.8 % initiated a second antineoplastic therapy. Of the CCRT-first patients, 27/143 with a complete response had subsequent recurrent disease (median rwRFS not reached). 179 patients had persistent disease, among whom median (95 % confidence interval [CI]) rwPFS was 29.7 (16.9–59.3) months. Conclusion: In this study of United States-based clinical practices, most HR-LACC patients received CCRT as initial treatment. Many patients developed persistent disease after CCRT indicating a need for improved first treatment and maintenance options