Katherine B. Winfree

PRONOUNCE: Randomized, Open-Label, Phase III Study of First-Line Pemetrexed + Carboplatin Followed by Maintenance Pemetrexed versus Paclitaxel + Carboplatin + Bevacizumab Followed by Maintenance Bevacizumab in Patients ith Advanced Nonsquamous Non–Small-Cell Lung Cancer

Introduction: PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Methods: Patients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m2, carboplatin, area under the curve = 6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m2, carboplatin, area under the curve = 6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed. Results: Baseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio = 0.85, 90% confidence interval, 0.7–1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms. Conclusions: Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.

Safety, resource use, and quality of life in paramount: a phase III study of maintenance pemetrexed versus placebo after induction pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer

Introduction: In a phase III, randomized, double-blind study (PARAMOUNT), maintenance pemetrexed demonstrated significant benefit in advanced non–small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results. Methods: After four 21-day cycles of pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance pemetrexed 500 mg/m2 plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D). Results: Frequently reported grade 3 to 4 drug-related toxicities with maintenance pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p < 0.006). No significant differences in drug-related grade 3 to 5 toxicities were observed with long-term pemetrexed exposure (>6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p <0.001), anti-infectives (25.3% versus 16.7%; p = 0.028), and hospitalizations because of study drug (8.4% versus 3.3%, p = 0.028) than placebo-treated patients did. No significant treatment-by-time interactions, overall treatment differences, or clinically relevant changes from baseline were observed in EQ-5D scores during treatment. Conclusions: Long-term use of continuation maintenance pemetrexed was well tolerated; resource use was low, corresponding with known pemetrexed toxicities. The EQ-5D results demonstrate that patients tolerate long-term maintenance pemetrexed without worsening QoL.

Quality of life scores as prognostic factors of overall survival in advanced head and neck cancer: Analysis of a phase III randomized trial of pemetrexed plus cisplatin versus cisplatin monotherapy

OBJECTIVES We examined the prognostic factors (clinical, demographic, and health-related quality of life [HRQoL]) of overall survival (OS) and progression-free survival (PFS) in patients with recurrent/metastatic head and neck cancer (HNC) who were treated with pemetrexed plus cisplatin versus cisplatin in a phase III, multinational, randomized trial. MATERIALS AND METHODS Five subscales of the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-H&N), modified to score from 0 to 100, measured HRQoL at baseline and during treatment. Univariate and multivariate Cox proportional hazards models were used on data pooled from both treatment arms to assess the effect of baseline prognostic factors on OS and PFS. RESULTS Of 795 patients randomized, 704 completed a baseline FACT-H&N and were included in the analysis. Age (<65 versus ⩾65; HR=0.74, 95% CI: 0.61-0.90), race (Caucasian versus non-Caucasian; HR=0.83, 95% CI: 0.70-0.98 per table), Eastern Cooperative Oncology Group performance status (ECOG PS; 0/1 versus 2; HR=0.44, 95% CI: 0.35-0.56), prior surgery/radiotherapy in the last 6months (no versus yes; HR=0.74, 95% CI: 0.61-0.90), and primary site of disease (oral cavity versus other; HR=1.37, 95% CI: 1.15-1.63) were significantly prognostic of OS in univariate models, as were baseline scores on four FACT-H&N subscales (physical well-being, emotional well-being, functional well-being, additional concerns-H&N; HRs=0.82-0.94; all P⩽0.002). In multivariate models, significant prognostic factors were age (HR=0.78); race (HR=0.76 per table); ECOG PS (HR=0.56); prior surgery/radiotherapy (HR=0.76); and baseline scores of the FACT-H&N subscales of physical well-being, social/family well-being, and additional concerns-H&N (HRs=0.89-0.94; all P⩽0.014 per table). CONCLUSIONS The results suggest that baseline HRQoL scores are prognostic indicators of OS in recurrent/metastatic HNC in addition to other known clinical and demographic indicators. HRQoL might be considered as a stratification factor in randomized clinical trials of recurrent/metastatic HNC.

Baseline quality of life and performance status as prognostic factors in patients with extensive-stage disease small cell lung cancer treated with pemetrexed plus carboplatin vs. etoposide plus carboplatin

BACKGROUND Small cell lung cancer (SCLC) is associated with poor prognosis due to its early metastatic potential and lack of improved outcomes with newer cytotoxic agents. Identifying factors associated with clinical outcomes can help clinicians determine which patients are more likely to benefit from therapy. Functional Assessment of Cancer Therapy (FACT) subscales and Eastern Cooperative Oncology Group performance status (ECOG PS) were retrospectively analyzed as prognostic factors for overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage disease (ED)-SCLC. METHODS Using data from a Phase III trial of pemetrexed-carboplatin vs. etoposide-carboplatin, the effect of the prognostic factors on OS and PFS was analyzed via Cox models. The Kaplan-Meier method was used to estimate OS and PFS parameters for the prognostic subgroups (defined by baseline FACT scores and ECOG PS). RESULTS Patients with higher baseline FACT-General (FACT-G) score (≥ median) had significantly higher OS (hazard ratio [HR]=0.62, P<.0001) and PFS (HR=0.83, P=.032) compared with patients with lower FACT-G score (<median). Similar results were observed for higher baseline physical well-being (PWB) and functional well-being (FWB) scores. For OS, there was a significant interaction between PS and FACT-PWB score (P=.005). In patients with PS=2 and higher FACT-PWB scores at baseline, a 48% reduction in the risk of death (P=.025) and nearly 3-month longer median OS were estimated. CONCLUSIONS Higher baseline FACT-G, FACT-PWB, and FACT-FWB scores were found to be favorable prognostic factors for survival in ED-SCLC. Higher FACT-PWB scores at baseline predicted better survival for patients with poorer PS.

Treatment patterns and economic burden of metastatic and recurrent locally-advanced head and neck cancer patients

Abstract Objective: To characterize treatment patterns and measure the economic burden associated with metastatic (mHNC) and recurrent, locally-advanced head and neck cancer (rHNC). Methods: Administrative claims from Medicare- and privately-insured individuals during 2004–2008 were used in this retrospective database study of patients with advanced HNC. Patients diagnosed with HNC were matched 1:1 to cancer-free controls to measure the incremental economic burden of HNC. Outcomes of interest were measured during the 6 months following the date of a secondary tumor diagnosis for metastatic patients or the date of a diagnosis indicating rHNC. To assess treatment patterns, HNC patients were evaluated for the use frequency of treatments (radiotherapy, chemotherapy and surgery). Costs were reported in 2008 US

Cost effectiveness of first-line pemetrexed plus platinum compared with other regimens in the treatment of patients with nonsquamous non-small cell lung cancer in the US outpatient setting

from a third-party payer perspective and were analyzed using generalized linear models and two-part regression models adjusting for differences in age and baseline Charlson Comorbidity Index (excluding cancer diagnoses) between the HNC and control cohorts. Components of cost included inpatient, outpatient and other medical services as well as pharmacy costs. Results: The mHNC cohort consisted of 1042 patients and the rHNC cohort included 324 patients. The most common treatments for mHNC patients were supportive care (90.2%), radiation therapy (48.5%), surgery (41.9%) and chemotherapy (38.3%). Patients with rHNC frequently received HNC-related supportive care (71.0%), radiation therapy (67.9%) and chemotherapy (27.2%); HNC-related surgery was infrequent (12.7%) during the study period. The 6-month incremental adjusted total costs were

Cost-effectiveness of first-line induction and maintenance treatment sequences in non-squamous non-small cell lung cancer (NSCLC) in the U.S.

60,414 per patient for mHNC and

Quality of Life Analyses from the Randomized, Open-Label, Phase III PointBreak Study of Pemetrexed-Carboplatin-Bevacizumab followed by Maintenance Pemetrexed-Bevacizumab Versus Paclitaxel-Carboplatin-Bevacizumab followed by Maintenance Bevacizumab in Patients with Stage IIIB or IV Nonsquamous Non–Small-Cell Lung Cancer

21,141 per patient for rHNC (p < 0.0001). Approximately 46–58% of the incremental cost was attributable to outpatient visits, 27–37% to inpatient costs and 11–13% to pharmacy, depending on the HNC cohort. Limitations: The identification of mHNC/rHNC was based on diagnosis codes and treatment patterns with the limitation of the claims database. Conclusions: Metastatic and recurrent, locally-advanced HNC patients frequently receive cancer-related treatments and incur substantial economic burden.

Treatment patterns and cost-effectiveness of first line treatment of advanced non-squamous non-small cell lung cancer in Medicare patients

This retrospective observational study evaluated cost effectiveness of first-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with pemetrexed/platinum (Pem/Plat) relative to paclitaxel/carboplatin (Pac/Carbo) and paclitaxel/carboplatin/bevacizumab (Pac/Carbo/Bev). Patients initiating first-line treatment from 2006 to 2009 were identified in electronic medical records of 20 US oncology practices. Pem/Plat patients were matched 1:1 on important characteristics with Pac/Carbo and Pac/Carbo/Bev patients and followed for 1 year to assess progression, survival, and costs. Bootstrapping was used to calculate the probability of falling within quadrants of the incremental cost-effectiveness plane. Kaplan-Meier analysis and Cox proportional hazards regression modeling were also performed. Three hundred Pem/Plat patients (mean age, 67.6 years; male, 56.0%; PS 0/1, 71.0%) were matched with 300 patients in the other cohorts. Median PFS was 134 days (Pem/Plat) versus 106 days (Pac/Carbo) (hazard ratio [HR]: 0.67, P < 0.001) and 126 days (Pac/Carbo/Bev) (HR: 0.68, P < 0.001). Median OS was 298 days (Pem/Plat) versus 218 days (Pac/Carbo) (HR: 0.88, P = 0.08) and 271 days (Pac/Carbo/Bev) (HR: 0.93, P = 0.31). Pem/Plat therapy costs were higher versus Pac/Carbo (

Cost Analyses in the US and Japan: A Cross-Country Comparative Analysis Applied to the PRONOUNCE Trial in Non-Squamous Non-Small Cell Lung Cancer

21,841 higher PFS;