Nina Helbekkmo

Vinorelbine/carboplatin vs gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity

This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB/IV and WHO performance status 0–2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m−2 or gemcitabine 1000 mg m−2 on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy and every 8 weeks until 49 weeks. During 14 months, 432 patients were included (VC, n=218; GC, n=214). Median survival was 7.3 vs 6.4 months, 1-year survival 28 vs 30% and 2-year survival 7 vs 7% in the VC and GC arm, respectively (P=0.89). HRQOL, represented by global QOL, nausea/vomiting, dyspnoea and pain, showed no significant differences. More grade 3–4 anaemia (P<0.01), thrombocytopenia (P<0.01) and transfusions of blood (P<0.01) or platelets (P<0.01) were observed in the GC arm. There was more grade 3–4 leucopoenia (P<0.01) in the VC arm, but the rate of neutropenic infections was the same (P=0.87). In conclusion, overall survival and HRQOL are similar, while grade 3–4 toxicity requiring interventions are less frequent when VC is compared to GC in advanced NSCLC.

Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group

Background:The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved.Methods:Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity.Results:Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year survival was 34.0% and 53.2% (P<0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (P<0.05).Conclusion:Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity.

Treatment outcome in performance status 2 advanced NSCLC patients administered platinum-based combination chemotherapy.

BACKGROUND There is no consensus regarding chemotherapy to patients with advanced NSCLC (ANSCLC) and performance status (PS) 2. Using data from a national multicenter study comparing two third-generation carboplatin-based regimens in ANSCLC patients, we evaluated the outcome of PS 2 patients. PATIENTS AND METHODS The 123 PS 2 patients were compared to 309 PS 0/1 patients regarding survival, quality of life (QOL) and treatment toxicity. RESULTS PS 2 patients had lower haemoglobin, lower global QOL and more pain, nausea/vomiting and dyspnea at inclusion. 68% of PS 2 patients received three chemotherapy courses vs. 85% in the PS 0/1 group (P<0.01). Median and 1-year survival were lower in the PS 2 group, 4.5 vs. 8.9 months and 10% vs. 37% (P<.01). More PS 2 patients needed blood transfusions (P=0.03) and hospitalization (P<0.01). In contrast, PS 2 patients had better relief of pain and dyspnea, and tended to a better global QOL and did not experience more leucopoenia, infections or bleeding. CONCLUSIONS Despite shorter survival, treatment toxicity was acceptable and PS 2 patients achieved better improvement of pain and dyspnea and tended to better global QOL when compared to PS 0/1 patients.

Poor Prognosis Patients with Inoperable Locally Advanced NSCLC and Large Tumors Benefit from Palliative Chemoradiotherapy: A Subset Analysis from a Randomized Clinical Phase III Trial

Introduction: Poor prognosis patients with bulky stage III locally advanced non–small-cell lung cancer may not be offered concurrent chemoradiotherapy (CRT). Following a phase III trial concerning the effect of palliative CRT in inoperable poor prognosis patients, this analysis was performed to explore how tumor size influenced survival and health-related quality of life (HRQOL). Methods: A total of 188 poor prognosis patients recruited in a randomized clinical trial received four courses intravenous carboplatin day 1 and oral vinorelbine day 1 and 8, at 3-week intervals. The experimental arm (N = 94) received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. This subset study compares outcomes in patients with tumors larger than 7 cm (N = 108) versus tumors 7 cm or smaller (N = 76). Results: Among those with tumors larger than 7 cm, the median overall survival in the chemotherapy versus CRT arm was 9.7 and 13.4 months, respectively (p = 0.001). The 1-year survival was 33% and 56%, respectively (p = 0.01). Except for a temporary decline during treatment, HRQOL was maintained in the CRT arm, regardless of tumor size. Among those who did not receive CRT, patients with tumors larger than 7 cm experienced a gradual decline in the HRQOL. The CRT group had significantly more esophagitis and hospitalizations because of side effects regardless of tumor size. Conclusion: In patients with poor prognosis and inoperable locally advanced non–small-cell lung cancer, large tumor size should not be considered a negative predictive factor. Except for performance status 2, patients with tumors larger than 7 cm apparently benefit from CRT.

Chemotherapy and quality of life in NSCLC PS 2 patients

Introduction. Nearly 40% of patients with advanced NSCLC are in performance status (PS) 2. These patients have a shorter life expectancy than PS 0/1 patients and they are underrepresented in clinical trials. Data on how platinum-based combination chemotherapy affects Health Related Quality of Life (HRQOL) of patients with PS 2 are scarce and the treatment of this important group of patients is controversial. Methods. A national multicenter phase III study on platinum based chemotherapy to 432 advanced NSCLC patients included 123 patients with PS 2. To explore the treatment impact on HRQOL, the development of HRQOL during the first nine weeks were compared between PS 2 and PS 0/1 patients. We used the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Standardized area under the curve for all HRQOL items, and HRQOL responses classified as better, stable or worse, were compared between the groups. Results. Whereas the demographic data at baseline were well balanced between the groups, the PS 2 patients had significantly worse function and more severe symptoms than the PS 0/1 patients. In response to combination chemotherapy, the PS 2 patients had a more profound improvement of global QOL, cognitive function, fatigue, dyspnea, sleeping problems and appetite loss in comparison to the PS 0/1 group. Conclusions. PS 2 NSCLC patients seem to achieve valuable HRQOL benefits from platinum-based combination therapy. Prospective clinical studies with predefined HRQOL outcomes in PS 2 patients are needed to confirm these findings.

Pembrolizumab as second-line therapy in non-small cell lung cancer in northern Norway: budget impact and expected gain—a model-based analysis

Background Pembrolizumab is a new drug approved in several countries for second-line therapy in non-small cell lung cancer (NSCLC) being programmed cell death ligand (PD-L1) positive. This drug has a high cost, and the cost-effectiveness ratio has been debated. Patients and methods The budget impact to the Northern Norwegian Regional Health Authority trust of implementing pembrolizumab in second-line therapy in patients with PD-L1-positive NSCLC was calculated. A model was developed employing data from the Cancer Registry of Norway, the KEYNOTE-010 study, the price list from The Hospital Pharmacy of North Norway, the cost of analysing PD-L1 expression and the cost of travelling. Todays cost of second-line therapy was compared with the new standard employing pembrolizumab. The sale price of pembrolizumab in Norway was not published due to price confidentiality. Norwegian krone (NKr) was converted into Euros (€) at a rate of 1€=Nkr 8.8138. (Bank of Norway, 21 February 2017). Results 105 new patients were identified available for pembrolizumab per year. The annual cost of pembrolizumab was €5.2 million, hospital pharmacy administration costs €0.1 million, PD-L1 testing €0.3 million, oncologist/pulmonologist/nurses €0.2 million, radiology €0.06 million and transportation €0.4 million. Savings due to avoided present second-line therapy was calculated €0.4 million. Consequently, the cost of implementing pembrolizumab was €5.5 million and the annual budget impact was €5.0 million. A mean gain of at least 9 months per patient treated was necessary to make pembrolizumab cost-effective. Conclusions The net budget impact of pembrolizumab was €5.0 million. The expenditure could not be indicated cost-effective. Price confidentiality is a growing problem in health economics and it has become a ‘menu without prices’ setting.