PURPOSE For patients with resectable stage IIIA(N2) non–small-cell lung cancer, neoadjuvant chemotherapy with cisplatin and docetaxel followed by surgery resulted in a 1-year event-free survival (EFS) rate of 48% in the SAKK 16/00 trial and is an accepted standard of care. We investigated the additional benefit of perioperative treatment with durvalumab. METHODS Neoadjuvant treatment consisted of three cycles of cisplatin 100 mg/m2 and docetaxel 85 mg/m2 once every 3 weeks followed by two doses of durvalumab 750 mg once every 2 weeks. Durvalumab was continued for 1 year after surgery. The primary end point was 1-year EFS. The hypothesis for statistical considerations was an improvement of 1-year EFS from 48% to 65%. RESULTS Sixty-eight patients were enrolled, 67 were included in the full analysis set. Radiographic response rate was 43% (95% CI, 31 to 56) after neoadjuvant chemotherapy and 58% (95% CI, 45 to 71) after sequential neoadjuvant immunotherapy. Fifty-five patients were resected, of which 34 (62%) achieved a major pathologic response (MPR; ≤ 10% viable tumor cells) and 10 (18%) among them a complete pathologic response. Postoperative nodal downstaging (ypN0-1) was observed in 37 patients (67%). Fifty-one (93%) resected patients had an R0 resection. There was no significant effect of pretreatment PD-L1 expression on MPR or nodal downstaging. The 1-year EFS rate was 73% (two-sided 90% CI, 63 to 82). Median EFS and overall survival were not reached after 28.6 months of median follow-up. Fifty-nine (88%) patients had an adverse event grade ≥ 3 including two fatal adverse events that were judged not to be treatment-related. CONCLUSION The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non–small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.
De novo concurrent ALK/KRAS co-alterations were associated with resistance to ALK TKI treatment in seven out of eight patients. In patients with ALK/EGFR co-alterations, outcomes with ALK and EGFR TKIs seem inferior to what would be expected in patients with either alteration alone, but further studies are needed to clarify which patients with ALK/EGFR co-alterations may still benefit from the respective TKI.
BackgroundBesides conventional adjuvant therapies, many breast cancer survivors engage in various activities like exercise, diet and complementary and alternative medicine (CAM) in order to improve their prognosis. Little is known about specific interests and willingness to participate in institutional programs (e.g. exercise classes).MethodsWe conducted a cross-sectional study in patients with early breast cancer assessing current physical activity (PA, e.g. 30 minutes brisk walking), attention to eating habits (“diet”), use of CAM, and interest in learning more about these fields. Patients indicating interest in PA counselling received a voucher for a free instruction by a certified physiotherapist. Data were analysed for factors predictive for engagement in the three fields using a stepwise multivariate logistic approach.ResultsOf 342 consecutive patients, 232 (69%) reported to be physically active more than once per week, 299 (87%) paying special attention to nutrition (in most cases fruits, “balanced diet”, low fat), and 159 (46%) use of CAM (vitamins, special teas, homeopathy, herbal medicine, mistletoe). Factors predictive for PA were use of CAM, higher age, and fewer worries about the future. Swiss nationality at birth, physical activity and higher education were predictive for diet; whereas physical activity, higher education and lower age were predictive for use of CAM. No associations between any of the above variables and breast cancer characteristics were found. Around half of the patients reported interest in receiving more information and willingness to attend special counselling. Of 166 vouchers, only 7 (4%) were eventually utilized.ConclusionsA high proportion of breast cancer survivors report PA, following a specific diet and use of CAM. There were no disease related factors associated with such pursuits, but an association between patient related factors and these fields was observed suggesting general health awareness in some patients. Around half of the patients were interested in more information and indicated willingness to participate in institutional programs. Impact on disease specific and general health including health economic aspects warrants further research.
We performed the current study to investigate the influence of 2 different hydroxyethyl starch (HES) solutions, the novel medium molecular weight HES 130/0.4 (6%) and HES 200/0.5 (6%), on plasma and whole blood viscosity in vitro and ex vivo in patients with severe head injury. For the in vitro experiments, blood was incubated with increasing concentrations (0%-50% vol/vol plasma) of either 6% HES 130/0.4 or 6% HES 200/0.5 solution. Plasma viscosity and whole blood viscosity (hematocrit [Hct] 45%) at high (94.5 s(-1)) and low (0.1 s(-1)) shear rates were determined. Both HES solutions increased plasma viscosity, but HES 130/0.4 to a lesser extent than HES 200/0.5. Whole blood viscosity was significantly less with HES 130/0.4 than with HES 200/0.5 at concentrations of 37.5% and larger. In the ex vivo study on 31 patients with severe cranio-cerebral trauma treated randomly with either HES 130/0.4 or HES 200/0.5 over several days, frozen plasma samples were thawed and plasma viscosity was determined. Blood was reconstituted with normal erythrocytes (0, Rh neg, Hct 45%) for whole blood viscosity measurements. In both groups plasma and blood viscosity tended to increase over time without statistical significance. Although the prominent effects found in vitro are not in keeping with the ex vivo data, they are likely to reflect the true clinical situation during repetitive, large-dose HES administration. We therefore conclude that HES 130/0.4 may have hemorheological advantages over conventional HES 200/0.5 when used in large quantities.
Background: Systemic second-and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6e9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. Patients and methods: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m 2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS 12wks ), was met if achieved by !21 pts (p0 35% versus p1 !55%). Results: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed 6 months after first-line chemotherapy. At data cut-off PFS 12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P ¼ 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2e7.4). No significant difference in PFS 12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within 6 months after first-line chemotherapy. Lurbinectedin-related grade 3e4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). Conclusions: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. ClinicalTrials.gov Identifier: NCT03213301
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