Barbara Graham

Randomized Phase III Trial of Vinorelbine Plus Cisplatin Compared With Observation in Completely Resected Stage IB and II Non–Small-Cell Lung Cancer: Updated Survival Analysis of JBR-10

PURPOSE Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non-small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data. PATIENTS AND METHODS Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis. Results Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms. CONCLUSION Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm.

Age and Comorbidity As Independent Prognostic Factors in the Treatment of Non–Small-Cell Lung Cancer: A Review of National Cancer Institute of Canada Clinical Trials Group Trials

PURPOSE This study analyzed patients enrolled in two large, prospectively randomized trials of systemic chemotherapy (adjuvant/palliative setting) for non-small-cell lung Cancer (NSCLC). The main objective was to determine if age and/or the burden of chronic medical conditions (comorbidity) are independent predictors of survival, treatment delivery, and toxicity. PATIENTS AND METHODS Baseline comorbid conditions were scored using the Charlson comorbidity index (CCI), a validated measure of patient comorbidity that is weighted according to the influence of comorbidity on overall mortality. The CCI score (CCIS) was correlated with demographic data,(ie, age, sex, race), performance status (PS), histology, cancer stage, patient weight, hemoglobin, alkaline phosphatase, lactate dehydrogenase, outcomes of chemotherapy delivery (ie, type, total dose, and dose intensity), survival, and response. RESULTS A total of 1,255 patients were included in this analysis. The median age was 61 years (range, 34 to 89 years); 34% of patients were elderly (at least 65 years of age); and 31% had comorbid conditions at randomization. Twenty-five percent of patients had a CCIS of 1, whereas 6% had a CCIS of 2 or greater. Elderly patients were more likely to have a CCIS equal to or greater than 1 compared with younger patients (42% v 26%; P < .0001), as were male patients (35% v 21%; P < .0001) and patients with squamous histology (36% v 29%; P = .001). Although age did not influence overall survival, the CCIS appeared prognostic (CCIS 1 v 0; hazard ratio 1.28; 95%CI, 1.09 to 1.5; P = .003). CONCLUSION In these large, randomized trials, the presence of comorbid conditions (CCIS > or = 1), rather than age more than 65 years, was associated with poorer survival.

Quality-of-Life Outcomes for Adjuvant Chemotherapy in Early-Stage Non–Small-Cell Lung Cancer: Results From a Randomized Trial, JBR.10

PURPOSE Adjuvant chemotherapy for early stage non-small-cell lung cancer (NSCLC) is now the standard of care, but there is little information regarding its impact on quality of life (QOL). We report the QOL results of JBR.10, a North American, intergroup, randomized trial of adjuvant cisplatin and vinorelbine compared with observation in patients who have completely resected, stages IB to II NSCLC. PATIENTS AND METHODS QOL was assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and a trial-specific checklist at baseline and at weeks 5 and 9 for those who received chemotherapy and at follow-up months 3, 6, 9, 12, 18, 24, 30 and 36. A 10-point change in QOL scores from baseline was considered clinically significant. RESULTS Four hundred eighty-two patients were randomly assigned on JBR.10. A total of 173 patients (82% of the expected) in the observation arm and 186 (85% of expected) in the chemotherapy arm completed baseline QOL assessments. The two groups were comparable, with low global QOL scores and significant symptom burden, especially pain and fatigue, after thoracotomy. Changes in QOL during chemotherapy were relatively modest; fatigue, nausea, and vomiting worsened, but there was a reduction in pain and no change in global QOL. Patients in the observation arm showed considerable improvements in QOL by 3 months. QOL, except for symptoms of sensory neuropathy and hearing loss, in those treated with chemotherapy returned to baseline by 9 months. CONCLUSION The findings of this trial indicate that the negative effects of adjuvant chemotherapy on QOL appear to be temporary, and that improvements (with a return to baseline function) are likely in most patients.

Economic analysis of a randomized phase III trial of gemcitabine plus vinorelbine compared with cisplatin plus vinorelbine or cisplatin plus gemcitabine for advanced non-small-cell lung cancer (Italian GEMVIN3/NCIC CTG BR14 trial).

BACKGROUND/OBJECTIVE Non-platinum-based chemotherapy is a potential alternative to platinum doublet therapy for advanced non-small cell lung cancer in selected patients. We determined the cost-effectiveness of gemcitabine/vinorelbine (GEMVIN), versus cisplatin/gemcitabine (PG) or cisplatin/vinorelbine (PV), from a government payer perspective. METHODS Results from a randomized trial of GEMVIN versus PG or PV demonstrated no significant difference in global quality of life (primary endpoint) or overall survival between regimens, but superior progression-free survival for platinum-based regimens. A cost analysis was conducted using direct medical costs of treatment, grade 3 or 4 toxicity management, and investigations for the mean number of cycles per study arm. Costs were calculated using Canadian dollars in 2005, and then in 2013 after drug patent expiry. RESULTS In 2005, GEMVIN was the most expensive regimen (

Vinorelbine plus Cisplatin vs. Observation in Resected Non-Small-Cell Lung Cancer

6868), and PV the least expensive (

Adjuvant Vinorelbine and Cisplatin in Elderly Patients: National Cancer Institute of Canada and Intergroup Study JBR.10

4650), with an incremental cost of GEMVIN over PV of

Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer: An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature

2218. Diagnostic and administration costs did not differ significantly among regimens; GEMVIN had the lowest toxicity costs. The principal cost driver in 2005 was the cost of chemotherapy. In 2013, toxicity and administration costs emerged as major drivers; GEMVIN was less costly than PV and PG, (cost savings of

Updated survival analysis of JBR.10: A randomized phase III trial of vinorelbine/cisplatin versus observation in completely resected stage IB and II non-small cell lung cancer (NSCLC)

413 over PV). CONCLUSION Despite similar outcomes, GEMVIN was more expensive than PV or PG in 2005 because of higher chemotherapy costs. By 2013, after chemotherapy drug patent expiry, GEMVIN became the least costly regimen. Economic considerations in oncology change over time, and should be revisited in policy decisions based on cost.