A single-arm phase II trial of afatinib in pretreated patients with advanced NSCLC harboring a HER2 mutation: The ETOP NICHE trial.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9070-9070 ◽  
Author(s):  
Egbert F. Smit ◽  
Solange Peters ◽  
Rafal Dziadziuszko ◽  
Urania Dafni ◽  
Juergen Wolf ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Type I ◽  
Toxicity Profile ◽  
Lung Carcinogenesis ◽  
Serious Adverse Events ◽  
Control Disease

9070 Background: HER2mutations are identified in about 2% of lung adenocarcinomas and are critical for lung carcinogenesis. Afatinib is a selective and irreversible erbB family blocker with a manageable toxicity profile and promising results in small retrospective studies targeting HER2 in NSCLC. Methods: NICHE is a single-arm phase II trial exploring the potential of afatinib to control disease (complete or partial response or disease stabilization for ≥12 weeks) in pre-treated patients with advanced NSCLC harboring HER2 exon 20 mutations. Patients were treated with afatinib 40 mg/day p.o. until tumor progression or lack of tolerability. A Simon’s two stage phase II design was adopted, to explore whether afatinib can achieve a DCR of 75%, as opposed to a DCR of 50% under the current treatment options. For a 1-sided type I error of 10% and power of 80%, a total of 22 patients were needed. Results: As of 24 November 2016, 13 patients were recruited into the trial. Median age was 60 years, 69% female and 62% never smokers. The overall toxicity profile was in the expected range, with 5 patients experiencing serious adverse events (dyspnea, diarrhea, dehydration, epistaxis, pleural, pericardial and renal insufficiency). The median follow-up was 23 weeks (IQR 12 – 39). Three patients died and 10 were still on follow-up, among them five were still on treatment. Total of 7 patients (54%) achieved DC at 12-weeks, 3 patients had PD before and 3 at 12-weeks. The 12-week PFS was 51% (95% CI: 22 - 75) and the median PFS 13 weeks (95% CI 6 - NE). In the 1st stage analysis of the Simon’s design, with 9 patients included, the stopping boundary was crossed. Therefore and upon recommendations of the ETOP IDMC, recruitment into the trial was stopped prematurely in December 2016. Treatment and follow-up of the enrolled patients continues as planned. Conclusions: Based on the interim results, afatinib did not show the expected potential to control disease in this patient population. However in the full analysis set with 13 patients, clear signs of activity were seen. A comprehensive biomolecular analysis of the tumors is currently ongoing in order to identify a subgroup of patients who might still derive benefit from afatinib treatment. Clinical trial information: NCT02369484.

Phase II trial: Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7068-7068
Author(s):  
Dolores De la Mata ◽  
Monika Blake ◽  
Jesus Zamora Moreno ◽  
Omar Pena ◽  
Diana Flores-Estrada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Small Cell ◽  
Toxicity Profile ◽  
Small Cell Lung ◽  
Locally Advanced Nsclc

7068 Background: The treatment of choice for locally advanced non small cell lung cancer (NSCLC) is concurrent chemoradiation (CRT). However, efforts to improve treatment results include targeted therapy and the use of radiosensitizers. Nitroglycerin (NTG), a nitric oxide (NO) donor agent, reduces expression of Hypoxia-Induced Factor, which is associated to both chemo and radio resistance. Methods: This is phase II trial in patients with locally advanced NSCLC treated with chemotherapy (CT) based on cisplatin and vinorelbin with NTG concurrent with radiation therapy. A 25 mg NTG patch was administered to the patients during the first 5 days of each induction treatment cycle and during chemo-radiotherapy. Blood samples of VEGF were taken before any treatment and after two cycles of CT. The protocol is registered with ClinicalTrials.gov, number NCT00886405. Results: 35 patients were enrolled in this trial. Median Follow up was 16.6 months (SD ±13.6). Mean age was of 59.9 years (±10.8), 68.6% of the patients were smokers. ECOG status was 0 in 22.9%, 1 in 65.7% and 2 in 11.5%, respectively. Histopathology was adenocarcinoma in 68.6%, epidermoid in 17.1% and undifferentiated in 14.3%. Stage distribution was: IIIa, 57.6% and IIIb, 42.5%. All patients completed CRT treatment and four underwent surgical treatment. Toxicity profile related to NTG was grade 1 and 2 headache in 17.1%. Grade 3 and 4 toxicities were esophagitis (17.1%), neutropenia (62.9%), and nausea (5.7%). Sixty-four per cent of patients achieved partial response after CT and 75.8% after CRT. PFS was 11.8 months (95%, IC 7.8-15.6) and OS was 42.9 months (95%IC 31.3-52.1). After two cycles of CT, plasma VEGF levels were significantly lower (Median 132±79 vs. 53±78 pg/ml, p<0.001). No differences on PFS and OS were found between patients with a reduction ≥ 93 pg/ml (median of differences between VEGFR before and after chemotherapy). Conclusions: The addition of NTG to induction CT, and concurrent CRT on locally advanced NSCLC patients seems to increase the response rate, PFS and OS with an acceptable toxicity profile. A prospective trial is warranted to confirm these findings.

scholarly journals P86.16 Rationale of a Phase II Trial of Nivolumab Combined with Anlotinib in Advanced NSCLC Previously Treated with Immunotherapy

2021 ◽  
Vol 16 (3) ◽  
pp. S679-S680
Author(s):  
B. Han ◽  
B. Zhang ◽  
C. Shi ◽  
Z. Gao ◽  
H. Zhong ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Phase Ii Trial ◽  
Previously Treated

scholarly journals Isolated Pubic Ramus Fractures Are Serious Adverse Events for Elderly Persons: An Observational Study on 138 Patients with Fragility Fractures of the Pelvis Type I (FFP Type I)

2020 ◽  
Vol 9 (8) ◽  
pp. 2498 ◽  
Author(s):  
Pol Maria Rommens ◽  
Johannes Christof Hopf ◽  
Michiel Herteleer ◽  
Benjamin Devlieger ◽  
Alexander Hofmann ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Normal Population ◽  
Fragility Fractures ◽  
Type I ◽  
Elderly Persons ◽  
Serious Adverse Events ◽  
Pubic Ramus ◽  
One Year

Background: Fractures of the pubic ramus without involvement of the posterior pelvic ring represent a minority of fragility fractures of the pelvis (FFP). The natural history of patients suffering this FFP Type I has not been described so far. Material and methods: All patients, who were admitted with isolated pubic ramus fractures between 2007 and mid-2018, have been reviewed. Epidemiologic data, comorbidities, in-hospital complications, and one-year mortality were recorded. Of all surviving patients, living condition before the fracture and at follow-up was noted. Mobility was scored with the Parker Mobility Score, quality of life with the European Quality of Life 5 Dimensions 3 Level (EQ-5D-3L), subjective sensation of pain with the Numeric Rating Scale (NRS). Results: A consecutive series of 138 patients was included in the study. There were 117 women (84.8%) and 21 men (15.2%). Mean age was 80.6 years (SD 8.6 years). 89.1% of patients presented with comorbidities, 81.2% of them had cardiovascular diseases. Five patients (4%) died during hospital-stay. Median in-hospital stay was eight days (2–45 days). There were in-hospital complications in 16.5%, urinary tract infections, and pneumonia being the most frequent. One-year mortality was 16.7%. Reference values for the normal population of the same age are 5.9% for men and 4.0% for women. One-year mortality rate was 22.2% in the patient group of 80 years or above and 8.8% in the patient group below the age of 80. The rate of surviving patients living at home with or without assistance dropped from 80.5% to 65.3%. The median EQ-5D-Index Value was 0.62 (0.04–1; IQR 0.5–0.78). Reference value for the normal population is 0.78. Average PMS was 4 and NRS 3. Within a two-year period, additional fragility fractures occurred in 21.2% and antiresorptive medication was taken by only 45.2% of patients. Conclusion. Pubic ramus fractures without involvement of the posterior pelvis (FFP Type I) are serious adverse events for elderly persons. During follow-up, there is an excess mortality, a loss of independence, a restricted mobility, and a decreased quality of life. Pubic ramus fractures are indicators for the need to optimize the patient’s general condition.

Surveillance or Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial

2018 ◽  
Vol 36 (5) ◽  
pp. 446-453 ◽  
Author(s):  
Piet Ost ◽  
Dries Reynders ◽  
Karel Decaestecker ◽  
Valérie Fonteyne ◽  
Nicolaas Lumen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Specific Antigen ◽  
Phase Iii ◽  
Curative Intent ◽  
Free Survival ◽  
Local Progression ◽  
Randomized Phase Ii

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Sign in / Sign up

Export Citation Format

Share Document