How Do Elderly Poor Prognosis Patients Tolerate Palliative Concurrent Chemoradiotherapy for Locally Advanced Non–Small-Cell Lung Cancer Stage III? A Subset Analysis From a Clinical Phase III Trial

AbstractBackgroundIn a phase III trial of patients with unresectable, locally advanced, stage III non–small-cell lung cancer (NSCLC) with a poor prognosis, palliative concurrent chemoradiotherapy (CRT) provided a significantly better outcome than chemotherapy alone, except among performance status (PS) 2 patients. In the present subgroup analysis, we evaluated the effect on patients aged ≥ 70 years (42% of all included) compared with patients aged < 70 years enrolled in the trial.Patients and MethodsAll patients received 4 courses of intravenous carboplatin and oral vinorelbine. The experimental arm also received radiotherapy (42 Gy in 15 fractions). The included patients were required to have large tumors (> 8 cm), weight loss (> 10% within the previous 6 months) and/or PS 2.ResultsThe overall survival was increased among the CRT patients in both age groups, but the difference was significant only in patients aged < 70 years (median survival, 14.8 vs. 9.7 months; P = .001; age ≥ 70 years, median survival, 10.2 vs. 9.1 months; P = .09). Patients aged ≥ 70 years experienced better preserved health-related quality of life (QOL) and significantly less hematologic toxicity. The 2- and 3-year survival was significantly increased in both age groups receiving CRT.ConclusionElderly patients aged ≥ 70 years with unresectable, stage III, locally advanced, NSLCL and a poor prognosis can tolerate CRT with the doses adjusted to age and palliative intent. These results indicate that CRT can provide both survival and QOL benefits in elderly patients, except for those with PS 2 or worse. The male predominance in the ≥ 70-year-age group and the reduced chemotherapy intensity for the patients aged > 75 years might explain the lack of significant survival improvement among those patients aged ≥ 70 years

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 (Po0.01). One-year survival was 34.0% and 53.2% (Po0.01). 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 (Po0.05). Conclusion: Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity

Advanced Non-small Cell Lung Cancer Effects of Chemotherapy and Impact on Health Related Quality of Life

Avhandlingen presenterer behandlingseffekt, bivirkninger og livskvalitet hos lungekreftpasienter som får moderne cellegiftbehandling. Pasientene med performance status (PS) 2 er etterpå vurdert separat. Avhandlingens tittel er ”Advanced non-small cell Lung Cancer – Effects of Chemotherapy and Impact on Health Related Quality of Life”. Den ble forsvart for graden PhD 13.03.2009. På verdensbasis er lungekreft den vanligste kreftsykdommen og den som forårsaker flest kreftrelaterte dødsfall. I Norge dør rundt 2000 mennesker av lungekreft hvert år. De fleste pasientene har langtkommet sykdom og kan ikke kureres. Målet med behandling er forlengelse av livet og best mulig livskvalitet. Avhandlingen tar utgangspunkt i VING-studien som ble gjennomført for å undersøke om det var ulik overlevelse, bivirkningsprofil og livskvalitet forbundet med to ulike cellegiftkombinasjoner. Ca 40 % av pasientene med langtkommet lungekreft er i dårlig allmenntilstand ved diagnosetidspunktet. I avhandlingen vurderes nytte og effekt av behandlingen for pasienter med PS 2. VING-studien var en nasjonal multisenter fase III studie utgått fra Norsk Lungekreftgruppe. Fra september 2003 til desember 2004 inkluderte 33 sykehus over hele landet 432 pasienter i studien. Pasientene fikk tre cellegiftkurer med tre ukers mellomrom, enten vinorelbin/carboplatin, eller gemcitabin/carboplatin. De fylte ut livskvalitetsskjema ved studiens start, før hver kur og deretter regelmessig ved kontroller. Sammenligning av de to behandlingsalternativene viste at overlevelse og livskvalitet var den samme, men at behandling med vinorelbin gir mindre tiltakskrevende bivirkninger. Som en konsekvens av dette, ble cellegiftkombinasjonen vinorelbin/carboplatin standardbehandling ved langtkommet lungekreft i Norge. Undersøkelser av hvordan PS 2 pasientene tålte behandlingen, viste at disse hadde gevinst av behandlingen. De oppnådde bedring i generell livskvalitet og pusteproblemer, samt mindre smerter, utmattelse, søvn- og appetittproblemer. Man frykter at cellegiftbehandling er en for stor påkjenning for de sykeste, men disse resultatene tyder på at man i større grad enn tidligere bør tilby behandling til pasienter som ønsker det

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 7cm (N = 108) versus tumors 7 cm or smaller (N = 76). Results: Among those with tumors larger than 7cm, 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 7cm 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

Does chemotherapy improve Quality of Life in NSCLC PS 2?

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

1 Norum J, et al . ESMO Open 2017; 2 :e000222. doi:10.1136/esmoopen-2017-000222 Open Access Abstr A ct Background P embrolizumab 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. Today’s 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 pa tients 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 transporta tion € 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

Substantial nation-wide improvement in lung cancer relative survival in Norway from 2000 to 2016

Introduction There have been significant changes in both diagnostic procedures and therapy for lung cancer since the beginning of the millennium. National incidence and survival data from 2000 through 2016 are studied. Methods National data on cancer incidence and vital status are virtually complete. Changes in incidence and survival are described by absolute numbers, percentages, and calculation of relative survival (period analysis). Results A total of 44,825 individuals were diagnosed with lung cancer in Norway in the study period. The number of incident cases increased with 49% whereas the prevalence increased with 136% from 2000 to 2016. Age-standardised rates rose markedly for women and levelled off for men. In 2016, adenocarcinoma accounted for about 50% of all lung cancers, slightly more for women than for men. The entity “NSCLC not otherwise specified” declined from 24% to 13%, and the fraction of patients with metastatic disease decreased from 54% to 46% during the period, for both sexes combined. The overall median survival time doubled for women and men, reaching 14.3 months and 11.4 months, respectively. For patients with metastatic disease, median survival time showed a small increase but remained less than 6 months. The overall 5-year relative survival increased from 16% to 26% in women and from 16% to 22% in men. The corresponding improvements for the subgroup of non-surgically treated cases with localised disease, were up from 25% to more than 40% in females, and from 10% to almost 40% in males. Conclusion There have been notable changes in incidence patterns and a remarkable improvement in survival for lung cancer over the last 17 years, most markedly for patients without distant metastases at the time of diagnosis. Hopefully, survival will improve even more when immunotherapy is implemented

Substantial nation-wide improvement in lung cancer relative survival in Norway from 2000 to 2016

Introduction There have been significant changes in both diagnostic procedures and therapy for lung cancer since the beginning of the millennium. National incidence and survival data from 2000 through 2016 are studied. Methods National data on cancer incidence and vital status are virtually complete. Changes in incidence and survival are described by absolute numbers, percentages, and calculation of relative survival (period analysis). Results A total of 44,825 individuals were diagnosed with lung cancer in Norway in the study period. The number of incident cases increased with 49% whereas the prevalence increased with 136% from 2000 to 2016. Age-standardised rates rose markedly for women and levelled off for men. In 2016, adenocarcinoma accounted for about 50% of all lung cancers, slightly more for women than for men. The entity “NSCLC not otherwise specified” declined from 24% to 13%, and the fraction of patients with metastatic disease decreased from 54% to 46% during the period, for both sexes combined. The overall median survival time doubled for women and men, reaching 14.3 months and 11.4 months, respectively. For patients with metastatic disease, median survival time showed a small increase but remained less than 6 months. The overall 5-year relative survival increased from 16% to 26% in women and from 16% to 22% in men. The corresponding improvements for the subgroup of non-surgically treated cases with localised disease, were up from 25% to more than 40% in females, and from 10% to almost 40% in males. Conclusion There have been notable changes in incidence patterns and a remarkable improvement in survival for lung cancer over the last 17 years, most markedly for patients without distant metastases at the time of diagnosis. Hopefully, survival will improve even more when immunotherapy is implemented

Atezolizumab and stereotactic body radiotherapy in patients with advanced non-small cell lung cancer: safety, clinical activity and ctDNA responses—the ComIT-1 trial

The introduction of immune checkpoint inhibitors has transformed the treatment landscape of metastatic non-small cell lung cancer. However, challenges remain to increase the fraction of patients achieving durable clinical responses to these drugs and to help monitor the treatment effect. In this phase II trial, we investigated the toxicity, systemic responses and circulating tumour DNA responses in patients (n = 21) with advanced non-small-cell lung cancer treated with atezolizumab and stereotactic body radiotherapy in the second or later line. We found the combined treatment to be safe with grade 3 toxicity reported in three patients. As the best overall response, four patients had a partial response, eight had stable disease and five had progressive disease. Median overall survival time was still not reached after a median follow-up of 26.5 months and 10/15 patients with programmed death-ligand 1 negative tumours were alive >18 months after the start of the study treatment. ctDNA was detectable at baseline in 11 patients. A rapid decline in ctDNA to <30% of baseline levels was seen in three patients, two of which were radiographic responders and one was considered clinically benefiting from therapy for almost 1 year