Background Indoleamine 2,3-dioxygenase 1 (IDO1) levels correlate with poor outcomes in urothelial carcinoma (UC). IDO1 and programmed death-ligand 1 (PD-L1) are often co-expressed. Epacadostat is a ...potent and highly selective inhibitor of IDO1. In a subgroup analysis of patients with advanced UC participating in a phase I/II study, epacadostat-pembrolizumab treatment produced an objective response rate (ORR) of 35%. Methods ECHO-303/KEYNOTE-698 was a double-blinded, randomized phase III study of adults with metastatic or unresectable locally advanced UC with recurrence or progression following first-line platinum-based chemotherapy. Participants were randomized to epacadostat 100 mg twice daily (BID) plus pembrolizumab or placebo plus pembrolizumab until completion of 35 pembrolizumab infusions, disease progression, or unacceptable toxicity. The primary endpoint was investigator-assessed ORR per Response Evaluation Criteria in Solid Tumors version 1.1. Results Target enrollment was 648 patients; enrollment was halted early based on efficacy results from the phase III ECHO-301/KEYNOTE-252 study in metastatic melanoma. Forty-two patients were randomized to each treatment arm. Median duration of follow-up was 62 days in each arm. The investigator-assessed ORR (unconfirmed) was 26.2% (95% CI 16.35-48.11) for epacadostat plus pembrolizumab and 11.9% (95% CI 4.67-29.50) for placebo plus pembrolizumab. Two complete responses were reported, both in the placebo-plus-pembrolizumab arm. Circulating kynurenine levels increased from C1D1 to C2D1 in the placebo-plus-pembrolizumab arm and numerically decreased in the epacadostat-plus-pembrolizumab arm. The safety profile of epacadostat plus pembrolizumab was similar to that of pembrolizumab monotherapy, although a numerically greater proportion of patients in the combination vs. control arm experienced treatment-related grade greater than or equal to 3 adverse events (16.7% vs. 7.3%). One patient in each arm died due to cardiovascular events, which were not deemed drug-related. No new safety concerns were identified for either agent. Conclusions Epacadostat plus pembrolizumab demonstrated anti-tumor activity and was generally tolerable as second-line treatment of patients with unresectable locally advanced or recurrent/progressive metastatic UC. Epacadostat 100 mg BID, when administered with pembrolizumab, did not normalize circulating kynurenine in most patients. Further study of combined IDO1/PD-L1 inhibition in this patient population, particularly with epacadostat doses that result in durable normalization of circulating kynurenine, may be warranted. Trial registration ClinicalTrials.gov, NCT03374488. Registered 12/15/2017. Keywords: IDO1, Epacadostat, PD-L1, Pembrolizumab, Urothelial carcinoma, Immune checkpoint inhibition, Randomized controlled study
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. We aimed to evaluate the clinicopathological features of the patients in Thrace and ...improve our management.
In this retrospective study, 68 patients with a diagnosis of GIST referred to Trakya University Medical School Hospital between 1997 and 2015 were evaluated.
The most common symptom was abdominal pain (38.2%) and the location was small-intestine (42.6%). Large masses had higher metastasis and relapse rate. The mean tumor size with relapse was 11.8 ± 3.8 cm meanwhile it was 6.5 ± 3.0 cm in non-relapsed patients (p = 0.01). The mean size of the tumor was 13.5 ± 4.4 in the metastatic group although this data was 8.8 ± 4.7 cm in the non-metastatic group (p = 0.01). With necrotic tumors, mitotic rate and size were higher. The mean mitosis count was 21.0 ± 3.6 in necrotic tumors and 7.2 ± 9.9 in non-necrotic tumors (p = 0.005). The mean size was 10.8 ± 5.0 cm in necrotic tumors and 5.6 ± 3.0 cm in non-necrotic tumors (p = 0.009). According to AFIP criteria, most of the patients were in the high-risk group (57.4%). Overall survival (OS) was longer in non-smokers and non-drinkers. Median OS was 80.16 months in non-smoker group (95% CI, 27.83–132.49) and 24.64 months (95% CI, 15.49–33.78) in the smoker group (p = 0.001). The median OS was 80.09 months in the non-drinker group (95% CI, 13.99–146.20) and 24.64 months (95% CI, 13.18–36.10) in drinker group (p = 0.05). Median OS in stomach GIST was 41.39 months, in small-intestine were 80.09 months and in the colon were 35.68 months (p = 0.032). Patients underwent surgery had longer overall-survival. Median OS was 80.09 months in patients undergone surgery and 16.98 months in patients had not been operated (p = 0.001). Overall survival was longer in GIST with mitotic rate <5/50HPF than with >5/50HPF. Median OS was 80.16 months in patients who had less than 5 mitosis and 39.22 months in higher mitotic rate (95% CI, 31.58–46.87) (p = 0.034). Overall survival was shorter in GIST with Ki-67 > 5% than with 5%>. Median OS was 80.16 months (95% CI, 28.80–49.65) in <5% and 39.22 months (95% CI, 28.80–49.65) in 5%≤ Ki-67 (p = 0.004).
The most important factors about the survival and prognosis of GIST are location, size, mitotic rate, Ki-67, necrosis and surgery status. Using tobacco/alcohol may be related to survival. This study should be further investigated with extensive data.
Background: This study was designed to estimate economic burden of lung cancer in Turkey from payer perspective based on expert panel opinion on practice patterns in clinical practice. Methods: In ...this cost of illness study, direct medical cost was calculated based on cost items related to outpatient visits, laboratory and radiological tests, hospitalizations/interventions, drug treatment, adverse events and metastasis. Indirect cost was calculated based on lost productivity due to early retirement, morbidity and premature death resulting from the illness, the value of lost productivity due to time spent by family caregivers and cost of formal caregivers. Results: Cost analysis revealed the total per patient annual direct medical cost for small cell lung cancer to be €8772), for non-small-cell lung cancer to be €10,167. Total annual direct medical cost was €497.9 million, total annual indirect medical cost was €1.1 billion and total economic burden of lung cancer was €1.6 billion. Hospitalization/interventions (41%) and indirect costs (68.6%) were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Conclusions: Our findings indicate per patient direct medical costs of small cell lung cancer and non-small-cell lung cancer to be substantial and comparable, indicating the substantial economic burden of lung cancer in terms of both direct and indirect costs. Our findings indicate that hospitalization/interventions cost item and indirect costs were the major cost drivers for total direct costs and the overall economic burden of lung cancer, respectively. Our findings emphasize the potential role of improved cancer prevention and early diagnosis strategies, by enabling cost savings related to drug treatment and metastasis management cost items, in sustainability of cancer treatments.
Background:
Abemaciclib is the first and only cyclin-dependent kinases 4 and 6 inhibitor approved for adjuvant treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor ...2-negative (HER2−), node-positive, and high-risk early breast cancer (EBC), with indications varying by geography. Premenopausal patients with HR+, HER2− tumors may have different tumor biology and treatment response compared to postmenopausal patients.
Objectives:
We describe the efficacy and safety of abemaciclib plus endocrine therapy (ET) for the large subgroup of premenopausal patients with HR+, HER2− EBC in monarchE.
Design:
Randomized patients (1:1) received adjuvant ET with or without abemaciclib for 2 years plus at least 3 additional years of ET as clinically indicated.
Methods:
Patients were stratified by menopausal status (premenopausal versus postmenopausal) at diagnosis. Standard ET (tamoxifen or aromatase inhibitor) with or without gonadotropin-releasing hormone agonist was determined by physician’s choice. Invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) by menopausal status were assessed at data cutoff on 1 April 2021 (median follow-up of 27 months).
Results:
Among randomized patients, 2451 (43.5%) were premenopausal and 3181 (56.4%) were postmenopausal. The choice of ET for premenopausal patients varied considerably between countries. Treatment benefit was consistent across menopausal status, with a numerically greater effect size in premenopausal patients. For premenopausal patients, abemaciclib with ET resulted in a 42.2% and 40.3% reduction in the risk of developing IDFS and DRFS events, respectively. Absolute improvement at 3 years was 5.7% for IDFS and 4.4% for DRFS rates. Safety profile for premenopausal patients was consistent with the overall safety population.
Conclusion:
Abemaciclib with ET demonstrated clinically meaningful treatment benefit for IDFS and DRFS versus ET alone regardless of menopausal status and first ET, with a numerically greater benefit in the premenopausal compared to the postmenopausal population. Safety data in premenopausal patients are consistent with the overall safety profile of abemaciclib.
The case of a patient who developed recurrent delayed immune-related pneumonitis (checkpoint inhibitor pneumonitis CIP) after immune checkpoint inhibitor (ICI) therapy for advanced osteosarcoma ...treatment is presented.
A 25-year-old female patient with metastatic osteosarcoma was treated with atezolizumab. Grade 2 pneumonitis developed three times in the first two years. Treatment was discontinued after recovery from the last episode of pneumonitis, which was complicated with secondary spontaneous pneumothorax. 2 years after discontinuation of immunotherapy, the patient again developed CIP. Pneumonitis symptoms were regressed with oral steroid therapy during follow-up and a stable disease response continued.
Immunotherapy can cause recurrent CIP at any time during the treatment period or after discontinuation of treatment.
Immune checkpoint inhibitors have been used in many types of cancer because they cause prolonged tumor responses. However, new side effects associated with these drugs have been identified. Pneumonia of the lung tissue may occur and recur during the use of these drugs or after their discontinuation. Patients with newly developing pulmonary symptoms during follow-up should be carefully monitored for this side effect.
Purpose
Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3–5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients ...with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E.
Methods
In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC.
Results
Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21–85) years. All patients’ histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051).
Conclusion
Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS.
Purpose
To assess the efficacy and safety of regorafenib versus rechallenge chemotherapy in previously treated mCRC patients in third-line setting.
Materials and methods
The data of 104 patients ...diagnosed with mCRC enrolled from 2010 to 2017 in six oncology centers were analyzed. Tumor treatment options were obtained from follow-up and treatment files. Rechallenge chemotherapy was identified as the re-use of the regimen which was previously administered to patients in one of the therapy lines and obtained disease control, these were the patients whose disease did not progress within 3 months.
Results
A total of 104 patients had received previously two lines of chemotherapy regimens for mCRC. Of these, 73 patients with mCRC who received regorafenib and 31 those who received rechallenge chemotherapy in third-line therapy were analyzed. Overall survival was better with rechallenge than it was with regorafenib (HR 0.29 95% CI 0.16–0.54,
p
< 0.001). Median OS was 12.0 months (95% CI 8.1–15.9) in rechallenge versus 6.6 months (95% CI 6.0–7.3) in regorafenib group (
p
< 0.001). Progression-free survival in the rechallenge group showed a higher median value of 9.16 months (95% CI 7.15–11.18) versus with that recorded in the regorafenib group of 3.41 months (95% CI 3.01–3.82), in favor of rechallenge chemotherapy. The most common adverse events of regorafenib was liver function test abnormality and hand–foot syndrome. Although grade 3 or 4 adverse events were similar, non-hematologic toxicities were more common than those of rechallenge.
Conclusions
Rechallenge is still a valuable option against regorafenib in patients who achieved disease control in one of the first two lines of therapy. Even though mCRC patients treated with regorafenib benefited clinically from this treatment, we revealed that chemotherapy rechallenge compared to regorafenib was more effective in the third-line treatment for mCRC patients.
Background
Transverse colon cancer (TCC) is a rare condition that accounts for 10% of all colon cancers. TCC was accepted more likely right-sided colon cancers. We aimed to investigate whether TCC ...differs from other colon tumors by using clinical, pathological, and molecular prognostic factors known to be important in colon cancer and if it differs in its own anatomical structure.
Patients and Methods
We evaluated local and locally advanced TCC patients between 2007 and 2020 years for demographics data, symptoms, treatment status, and histopathological and molecular features.
Results
Overall, 107 TCC patients were included in this study. According to the molecular data analysis of 44, 35, and 23 patients for MSI, RAS, and BRAF status, respectively, 7 (15.9%) were MSI-H, 13 (37.1%) were RAS mutant, and 11 (47.8%) had BRAF V600E mutation. The median follow-up time was 31.5 months. Median disease-free survival (DFS) was 5.19 months, and median OS was 88.3 months for the whole study population. The tumor stage was the most significant prognostic factor for DFS and OS. Although BRAF mutation was not a significant marker for DFS, it was an independent prognostic marker for OS (HR 3.90 95% CI 1.42–10.7). There were no statistically significant differences between proximal two-thirds and distal one-third tumor location.
Conclusion
TCC has molecular features and prognostic factors more likely RCC and no differences between proximal and distal sub-parts. BRAF V600E mutation status is an independent predictor of survival even in the early stages of TCC.
Sinonasal type hemangiopericytoma is a rare soft tissue tumor. Oncogenic osteomalacia (tumor-induced osteomalacia) is a rare syndrome that develops especially due to benign mesenchymal tumors. ...Nonspecific general bone pain and weakness delay the diagnosis and treatment of oncogenic osteomalacia, and it is difficult to determine the localization of the primary tumor causing oncogenic osteomalacia.
A 43-year-old male patient with nasal hemangiopericytoma with symptoms of oncogenic osteomalacia is presented. The patient had musculoskeletal complaints at first and was diagnosed with lumbar disc herniation and surgery was performed. When his complaints recurred 1 year later, he was re-evaluated and diagnosed with hypophosphatemic osteomalacia. Despite the various treatments he received, his complaints did not decrease but increased, so a detailed examination was decided. When the positive PHEX mutation and very high fibroblast growth factor 23 level were detected, PET-CT imaging was performed with a pre-diagnosis of possible oncogenic osteomalacia, but no finding was found. Then he was evaluated with Ga-68 DOTATATE, and the soft tissue mass filling the right ethmoidal sinus was detected. Due to the relation of the mass with surrounding structures, it was considered unsuitable for total excision and incomplete surgical excision was performed. Pathologic evaluation revealed sinonasal type hemangiopericytoma (glomangiopericytoma). A significant remission in the patient's complaints was observed after the operation. Young patients with osteomalacia with unknown causes should be evaluated for malignancy, and screening and further examinations should be performed.
PDF
