Programmed Death Ligand 1 (PD1) inhibitors are indicated as monotherapy in first line in patients with stage IIIB/C and IV NSCLC with PD-L1 expression of 50% or above and no EGFR mutation or ALK translocation. Still, under 50% of these patients respond to Immune Checkpoint Inhibitor (ICI) treatment, and there is a need to increase the fraction of patients benefiting from ICI treatment. UV1 is a therapeutic peptide-based cancer vaccine targeting human telomerase (hTERT). hTERT is essential for tumor growth, expressed at high levels in 85% of human tumors, but only sparsely expressed in normal tissues. UV1 induces the expansion of CD4 T cells that recognize specific sequences in the UV1 peptides, and essentially initiates an anti-tumor immune response. UV1 is combined with ICI based on a presumed synergistic activity between the two modalities, as ICI blocks inhibitory signals for a vaccine-induced T cell expansion and anti-tumor effector activity. The LUNGVAC-study (NCT05344209) is a randomized phase II, open-label, multicenter study evaluating efficacy and safety of anti-PD-1 treatment with or without UV1 vaccination in treatment-naïve patients with advanced or metastatic NSCLC, with PD-L1 ≥ 50%. At least one measurable lesion according to Recist 1.1, adequate organ function, ECOG performance status 0-2 and no other active cancer are main eligibility criteria. Stratification factors are squamous versus non-squamous, and ECOG 2 versus 0+1. Primary endpoint is progression free survival. To test the PFS null hypothesis with 80% power and a 1-sided alpha level of 0.10, a total of 97 PFS events are required. Based on data published for pembrolizumab monotherapy in KEYNOTE-024, to generate the required 97 PFS events, 138 patients will be randomized 1:1 to PD-1-inhibitor for a maximum of 2 years, with or without 8 injections with UV1 vaccine during the first 2 months. Inclusion time is estimated to be 18 months and patients will be followed thereafter for a minimum of 18 months. 20 patients are included as of September 2023. NCT05344209, EudraCT 2021-005729-25. Drammen Hospital, Vestre Viken Health Trust. Ultimovacs.
Abstract Purpose: The magnitude of the lung cancer epidemic combined with a change in proportion of gender and histological subtypes underscore the need to identify survival trends with a focus on underlying gender and histology variations as to better target prevention, screening, research and treatment efforts. Materials and Methods: We present complete national data on 40,118 lung cancer cases prospectively collected in The Cancer Registry of Norway the last 20 years (1988-2007). One and 5-year overall relative survival rates (RSR) were computed with 95% confidence intervals (CI) for each of the four successive 5-year periods of diagnosis stratified by gender, histological subgroups, age and stage. Results: A significant increase in overall 5-year RSR from the first to last 5-year period was observed for both men and women, in women from 10.1% (95% CI: 8.8% − 11.4%) to 15.4% (95% CI: 14% − 16.9%), and in men from 7.9% (95% CI: 7.1% − 8.7%) to 11.6% (95% CI: 10.5% − 12.8%). Five-year RSR were significantly higher for women than for men in all periods. Also 1-year RSR increased significantly, in women from 30.6% (95% CI: 28.7% − 32.5%) in 1988-1992 to 40.9% (95% CI: 39.5% − 42.4) in 2003-2007. In men, the corresponding rates were 28.2% (95% CI: 27%-29.4%) and 35.3% (95% CI: 34.2%-36.5%), respectively. Five-year RSR were lowest in patients diagnosed with small cell carcinoma, with no significant survival improvement over time in either gender, whereas in adenocarcinoma in women, and squamous cell carcinomas in both genders long-term relative survival rates improved significantly. Women diagnosed with adenocarcinoma had significantly higher 5-year RSR compared to men the three last 5-year periods studied. This gender difference was not significant in other histological subtypes. In both men and women, increasing age was associated with decreasing 1- and 5-year RSR. In women, a significant improvement in 5-year RSR was observed in all age groups from 50-79 years over the 20-year period. Women with localized disease at time of diagnosis had significantly better 5-year relative survival compared to men with localized disease throughout the period studied. In 2003-2007, 5-year RSR for localized disease were 51.8% (95% CI: 46.5%-56.8%) in women and 40.9% (95% CI: 36.1%-45.9%) in men. Conclusion: These complete national data highlight important prognostic characteristics of the lung cancer epidemic in Norway that presumably can be extrapolated to most developed countries. Improvements in short-term survival rates and modest but statistically significant improvements in long-term survival rates are encouraging; however long-time survival still remains poor. The apparent gender differences in survival should be a focus of further research. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 877.
Mesothelioma of the pleural or peritoneal cavities is one of the deadliest cancer types. The incidence of pleural subtypes has decreased over time due to decrease in asbestos exposure, and the current treatment landscape is changing due to introduction of novel therapies. In this study we have analysed contemporary epidemiological data of mesothelioma on a national level before the advent of immunotherapy.Complete national data on 1509 pleural and peritoneal malignant mesothelioma from the Cancer Registry of Norway from 2000 to 2019 are presented. Age standardised incidence and median survival were calculated.The age-standardised incidence of pleural mesothelioma among males has decreased from 1.7 per 100 000 in 2000-2004 to 1.1 in 2015-2019, whereas the incidence for females has been stable, lower than 0.3 per 100 000 throughout the period. Incidence of peritoneal mesotheliomas remained low, below 0.08 per 100 000. The female to male ratio among pleural mesotheliomas was 1:7 with no differences among morphological subtypes, whereas this ratio was 1:1.2 in peritoneal mesotheliomas. Median age at diagnosis for pleural mesothelioma was 73 years and 76 years for females and males respectively in the last 5-year period, and 67 years for peritoneal mesotheliomas of both sexes. Median survival among pleural mesotheliomas has been stable, with significantly worse prognosis among sarcomatoid subtype (5.4 months) compared to epithelioid subtype (15.8 months). Peritoneal mesothelioma of the epithelioid subtype, representing 38% of cases, had a median survival of 43.3 months, contrasting the non-epithelioid subtype of 5.1 months.Mesothelioma is still a significant disease with a dismal prognosis. Improvement in treatment is warranted.
Abstract Background The metastasis-promoting protein S100A4 induces expression of ephrin-A1 and osteopontin in osteosarcoma cell lines. The aim of this study was to investigate S100A4-mediated stimulation of ephrin-A1 and osteopontin in non-small cell lung cancer (NSCLC) cell lines, and to characterize the expression of these biomarkers in primary tumor tissue from NSCLC patients. Methods Four NSCLC cell lines were treated with extracellular S100A4, and ephrin-A1 and osteopontin expression was analyzed by real time RT-PCR and Western blotting. Immunohistochemical staining for S100A4, ephrin-A1 and osteopontin was performed on tissue microarrays containing primary tumor samples from a cohort of 217 prospectively recruited NSCLC patients, and associations with clinicopathological parameters were investigated. Results S100A4 induced ephrin-A1 mRNA and protein expression in adenocarcinoma, but not in squamous carcinoma cell lines, whereas the level of osteopontin was unaffected by S100A4 treatment. In primary tumors, moderate or strong immunoreactivity was observed in 57% of cases for cytoplasmic S100A4, 46% for nuclear S100A4, 86% for ephrin-A1 and 77% for osteopontin. Interestingly, S100A4 expression was associated with ephrin-A1 also in vivo, but there was no association between S100A4 and osteopontin. Expression levels of S100A4 and ephrin-A1 were significantly higher in adenocarcinomas compared to other histological subtypes, and S100A4-positive tumors were smaller and more differentiated than tumors without expression. Conclusions Our findings suggest that S100A4, ephrin-A1 and osteopontin are involved in the biology of NSCLC, and further investigation of their potential use as biomarkers in NSCLC is warranted.
Additional file 4: Supplementary Table 3. Patient characteristics by part of the cancer patient pathway for rectal cancer patients diagnosed in 2015–2016 in Norway.
