Pembrolizumab monotherapy has shown antitumor activity in patients with small-cell lung cancer (SCLC). The randomized, double-blind, phase III KEYNOTE-604 study compared pembrolizumab plus etoposide ...and platinum (EP) with placebo plus EP for patients with previously untreated extensive-stage (ES) SCLC.
Eligible patients were randomly assigned 1:1 to pembrolizumab 200 mg once every 3 weeks or saline placebo for up to 35 cycles plus 4 cycles of EP. Primary end points were progression-free survival (PFS; RECIST version 1.1, blinded central review) and overall survival (OS) in the intention-to-treat population. Objective response rate (ORR) and duration of response were secondary end points. Prespecified efficacy boundaries were one-sided
= .0048 for PFS and .0128 for OS.
Of the 453 participants, 228 were randomly assigned to pembrolizumab plus EP and 225 to placebo plus EP. Pembrolizumab plus EP significantly improved PFS (hazard ratio HR, 0.75; 95% CI, 0.61 to 0.91;
= .0023). Twelve-month PFS estimates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP. Although pembrolizumab plus EP prolonged OS, the significance threshold was not met (HR, 0.80; 95% CI, 0.64 to 0.98;
= .0164). Twenty-four-month OS estimates were 22.5% and 11.2%, respectively. ORR was 70.6% in the pembrolizumab plus EP group and 61.8% in the placebo plus EP group; the estimated proportion of responders remaining in response at 12 months was 19.3% and 3.3%, respectively. In the pembrolizumab plus EP and placebo plus EP groups, respectively, any-cause adverse events were grade 3-4 in 76.7% and 74.9%, grade 5 in 6.3% and 5.4%, and led to discontinuation of any drug in 14.8% and 6.3%.
Pembrolizumab plus EP significantly improved PFS compared with placebo plus EP as first-line therapy for patients with ES-SCLC. No unexpected toxicities were seen with pembrolizumab plus EP. These data support the benefit of pembrolizumab in ES-SCLC.
•Early detection of local recurrence and distant metastasis in breast cancer can be curable with early intervention.•The role of serum tumor markers in breast cancer prognosis remains ...controversial.•Serum carcinoembriyonic antigen (CEA) and cancer antigen 15–3 (CA15–3) remain the most frequently used biomarkers in breast cancer.•Recent guidelines are recommended CA15–3 and CEA for practical use in the early detection of recurrent disease.•They are considered as a cheap and accessible way of predicting breast cancer prognosis.•More sensitive cut-off values for each marker are needed to be validated.
We aimed to evaluate the association of serum carcinoembryonic antigen (CEA) and cancer antigen 15–3 (CA 15–3) levels with clinicopathological parameters in patients with breast cancer (BC) and their efficiency for the prediction of recurrence.
Methods: The records of 482 female patients with breast cancer diagnosis followed in Medical Oncology and Radiation Oncology clinics of Kartal Dr. Lutfu Kirdar Education and Research Hospital were evaluated retrospectively.
The median age of the patients was 49. CEA levels were significantly higher in postmenopausal patients (p = 0.022). There was no association between CEA and CA 15–3 levels and nodal involvement (p = 0.689, 0.379; respectively). CEA levels were significantly higher in hormone receptor-positive patients (p = 0.007). HER2 negative patients had significantly higher levels of CEA and CA 15–3 (p = 0.017 and 0.011, respectively). The evaluation of metastatic patients showed that CEA and CA 15–3 levels before metastasis were significantly elevated (p = 0.016 ve 0.008, respectively). There was no relation between the metastasis site and CEA, CA 15–3 levels (p = 0.936, 0.201, respectively). Receiver operating characteristic (ROC) analysis was performed to determine the role of CEA and CA 15–3 levels in the prediction of metastasis, and cut-off values were 1.39 ng/ml and 14.54 U/ml, respectively. Sensitivities of CA 15–3 and CEA levels were 82.1% and 88.3%; specificities were 47.3% and 46.2%, respectively.
CEA and CA 15–3 are useful as tumor markers for early diagnosis of metastases, and their elevations were associated with unfavorable clinicopathological parameters of breast cancer patients. Since these markers are considered a cheap and accessible way of predicting breast cancer prognosis, there is an increasing interest in the prognostic value of serum levels of tumor markers in recent years. More sensitive cut-off values for each marker are needed to be validated with further studies.
Objective
Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. ...However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA).
Material and Method
We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT.
Results
Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis.
Conclusion
TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.
Although cancer patients have a high risk of exposing COVID-19 and developing severe complications, they have to receive active treatment. We aimed to determine the psychological conditions of cancer ...patients and shed light on the establishment of early psychological intervention and intervention policies by making specific recommendations.
We consecutively evaluated 385 cancer patients under treatment. Post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, stress, and associated sociodemographic/clinical characteristics were investigated. In addition, we applied depression-anxiety-stress-scale-21 (DASS-21) for the mental states of patients and Impact of Event-Scale-Revised (IES-R) for the psychological effects of Covid-19.
The mean age was 58 (18–88). 47.2% were psychologically distressful per DASS-21, and 39.3% were traumatic per IES-R scores. 71.9% stated the risk of getting COVID-19 was high since they had cancer, and 82% stated serious complications would develop if they had COVID-19 infection. Patients diagnosed for more than one year were more stressed, anxious, and depressive (p–value = 0.001,0.003,0.049, respectively). Singles were more stressed, depressed, and traumatized than couples (p-value = 0.001, 0.011, 0.001). In multivariate analysis, a significant correlation with being under psychiatric treatment before the pandemic was found for depression (OR: 3.743, 95 %CI: 1.790–7.827) anxiety (OR: 3.776–95 %CI: 1.945–7.332) and stress levels (OR: 4.129, 95 %CI: 1.728–9.866). Having relatives who died or received treatment for COVID-19(OR: 0.515,0.296–0.895) and being unmarried (OR: 2.445–95% CI: 1.260–4.747) predicts PTSD development.
When the psychological effects of the COVID-19 pandemic are manifesting strongly, cancer patients' anxiety and exposure levels are high. It is of great importance that clinicians understand needs, recognize psychological distress, and direct them to relevant departments for supportive care.
•Examined 385 cancer patients under active treatment during the COVID-19 era.•Investigated Post-traumatic stress disorder (PTSD) symptoms, depression, anxiety, stress, and associated sociodemographic/clinical characteristics.•Performed depression-anxiety-stress-scale-21 (DASS-21) for mental states, Impact of Event-Scale-Revised (IES-R) for psychological effects of Covid-19.•Being single, having relatives died of COVID-19 and being under psychiatric medication before the pandemic give tendency to depression and anxiety.
Covid-19, Cancer, Chemotherapy, Psychological impact.
This study aimed to determine the differences in clinicopathological features of Turkish patients with high-risk breast cancer based on the mutation status of two breast cancer susceptibility genes ...(BRCA1/2) .
This study enrolled patients with invasive breast cancer who have been evaluated for BRCA1/2 mutations due to the presence of high-risk factors admitted to two tertiary referral centers in Turkey. Clinical and histopathological features were analyzed in BRCA1 mutation carriers, BRCA2 mutation carriers, and non-carriers.
A total of 302 patients with a mean age of 44.2±9.9 (22-82) years were included. BRCA1/2 mutation was found in 75 (24%) patients, of whom 41 (13.6%) were BRCA1 mutation carriers and 37 (12.3%) were BRCA2 mutation carriers. Moreover, 104 (34.4%) and 4 (1.3%) patients had family history of breast and ovarian carcinoma, respectively. The rates of triple negativity (56.1%), histologic grade 3 (65.9%), and lymphovascular invasion (78%) were significantly higher in BRCA1 mutation carriers than in non-carriers and BRCA2 mutation carriers. Furthermore, 87% of triple-negative BRCA1 mutation carriers had histologic grade 3 tumors compared with 38.9% in non-triple-negative BRCA1 mutation carriers, and the difference was significant.
Findings of this study showed that BRCA1-related breast cancers represent a distinct group with unique pathological features, which are usually associated with a poor prognosis.
We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%.
In ...EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged ≥18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0–1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing.
Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17·9–not evaluable) with cemiplimab (n=283) versus 14·2 months (11·2–17·5) with chemotherapy (n=280; hazard ratio HR 0·57 0·42–0·77; p=0·0002). Median progression-free survival was 8·2 months (6·1–8·8) with cemiplimab versus 5·7 months (4·5–6·2) with chemotherapy (HR 0·54 0·43–0·68; p<0·0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3–4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy.
Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population.
Regeneron Pharmaceuticals and Sanofi.
The KEYNOTE-826 randomized clinical trial showed statistically significant and clinically meaningful survival benefits with the addition of pembrolizumab to chemotherapy with or without bevacizumab ...in patients with persistent, recurrent, or metastatic cervical cancer. Treatment effects in patient subgroups of the study population are unknown.
To assess efficacy outcomes in patient subgroups of KEYNOTE-826.
Exploratory subgroup analyses were conducted in a global, phase 3, randomized, double-blind, placebo-controlled clinical trial. Participants included women with persistent, recurrent, or metastatic adenocarcinoma, adenosquamous carcinoma, or squamous cell carcinoma of the cervix that had not been treated with systemic chemotherapy and was not amenable to curative treatment. This subanalysis was conducted from November 20, 2018, to May 3, 2021.
Pembrolizumab, 200 mg, every 3 weeks or placebo for up to 35 cycles plus chemotherapy (paclitaxel, 175 mg/m2, plus cisplatin, 50 mg/m2, or carboplatin AUC 5 area under the free carboplatin plasma concentration vs time curve) with or without bevacizumab, 15 mg/kg.
Overall survival (OS) and progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 in subgroups defined by use of bevacizumab (yes or no), choice of platinum (carboplatin or cisplatin), prior chemoradiotherapy (CRT) exposure only (yes or no), and histologic type (squamous or nonsquamous) in patients with programmed cell death ligand 1-positive tumors (defined as a combined positive score CPS ≥1) and in the intention-to-treat population.
A total of 617 patients (median age, 51 years; range, 22-82 years) were enrolled in the trial. In the CPS greater than or equal to 1 population, hazard ratios (HRs) for OS favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.62; 95% CI, 0.45-0.87) and without bevacizumab (HR, 0.67; 95% CI, 0.47-0.96), use of carboplatin (HR, 0.65; 95% CI, 0.50-0.85) and cisplatin (HR, 0.53; 95% CI, 0.27-1.04), with prior CRT only (HR, 0.56; 95% CI, 0.39-0.81) and without prior CRT only (HR, 0.72; 95% CI, 0.52-1.00), and squamous (HR, 0.60; 95% CI, 0.46-0.79) and nonsquamous (HR, 0.70; 95% CI, 0.41-1.20) histologic type. In the intention-to-treat population, HRs for OS also favored the pembrolizumab group in all subgroups: with bevacizumab (HR, 0.63; 95% CI, 0.47-0.87) and without bevacizumab (HR, 0.74; 95% CI, 0.53-1.04), use of carboplatin (HR, 0.69; 95% CI, 0.54-0.89) or cisplatin (HR, 0.59; 95% CI, 0.32-1.09), with prior CRT only (HR, 0.64; 95% CI, 0.45-0.91) and without prior CRT only (HR, 0.71; 95% CI, 0.53-0.97), and squamous (HR, 0.61; 95% CI, 0.47-0.80) and nonsquamous (HR, 0.76; 95% CI, 0.47-1.23) histologic type. Similar to OS, the addition of pembrolizumab prolonged PFS across all subgroups in the CPS greater than or equal to 1 and intention-to-treat populations.
The findings of this trial suggest that adding pembrolizumab to chemotherapy with or without bevacizumab improved OS across subgroups of patients with persistent, recurrent, or metastatic cervical cancer.
ClinicalTrials.gov Identifier: NCT03635567.
Objective: COVID-19 has rapidly spread and has become a pandemic by affecting the whole world. During this period, many scientific congresses and educational meetings had to be canceled because of ...preventive measures. In this report, we aimed to share our first live virtual congress experience, described its process of transformation from face to face to virtual congress and report the attendees and speakers’ satisfaction. Material and Methods: Eurasian Uro-oncological Association (EUA) decided to organize the 10th Eurasian Uro-oncology congress in June 2020 at Göbeklitepe, Şanlıurfa in Turkey. However, due to the COVID-19 pandemic, the organizing committee decided to organize the first virtual scientific congress in Turkey. The planned duration of the congress was reduced from 4 days to 2 days and each speaker was planned to give the speech online during the presentation via ZOOM program (San Jose, CA). Results: A total of 704 persons registered to the congress. It was the highest number of participants among whole congresses that was organized by EUA. In this congress, there were 199 oral presentations, 25 interactive e-posters and 12 video presentations. During the congress, each participant attended the congress for an average of 387 minutes. It was identified that the majority of the participants were quite satisfied with the program offered. In general, participants were fairly satisfied with the quality of images and sound, chat functionality, questions & answers section and technical support. Conclusion: In this report, we shared the outcomes of our first virtual congress experience in Turkey through the 10th Eurasian Uro-oncology Congress. Today, virtual congresses have become the "new normal" and offer cheaper events with larger participation in the comfort of home. Keywords: Congress, COVID-19, online, virtual, urology
Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)-positive metastatic or unresectable cervical cancer that has progressed during chemotherapy. We assessed the relative benefit of adding ...pembrolizumab to chemotherapy with or without bevacizumab.
In a double-blind, phase 3 trial, we randomly assigned patients with persistent, recurrent, or metastatic cervical cancer in a 1:1 ratio to receive pembrolizumab (200 mg) or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy and, per investigator discretion, bevacizumab. The dual primary end points were progression-free survival and overall survival, each tested sequentially in patients with a PD-L1 combined positive score of 1 or more, in the intention-to-treat population, and in patients with a PD-L1 combined positive score of 10 or more. The combined positive score is defined as the number of PD-L1-staining cells divided by the total number of viable tumor cells, multiplied by 100. All results are from the protocol-specified first interim analysis.
In 548 patients with a PD-L1 combined positive score of 1 or more, median progression-free survival was 10.4 months in the pembrolizumab group and 8.2 months in the placebo group (hazard ratio for disease progression or death, 0.62; 95% confidence interval CI, 0.50 to 0.77; P<0.001). In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65; 95% CI, 0.53 to 0.79; P<0.001). In 317 patients with a PD-L1 combined positive score of 10 or more, progression-free survival was 10.4 months and 8.1 months, respectively (hazard ratio, 0.58; 95% CI, 0.44 to 0.77; P<0.001). Overall survival at 24 months was 53.0% in the pembrolizumab group and 41.7% in the placebo group (hazard ratio for death, 0.64; 95% CI, 0.50 to 0.81; P<0.001), 50.4% and 40.4% (hazard ratio, 0.67; 95% CI, 0.54 to 0.84; P<0.001), and 54.4% and 44.6% (hazard ratio, 0.61; 95% CI, 0.44 to 0.84; P = 0.001), respectively. The most common grade 3 to 5 adverse events were anemia (30.3% in the pembrolizumab group and 26.9% in the placebo group) and neutropenia (12.4% and 9.7%, respectively).
Progression-free and overall survival were significantly longer with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic cervical cancer who were also receiving chemotherapy with or without bevacizumab. (Funded by Merck Sharp and Dohme; KEYNOTE-826 ClinicalTrials.gov number, NCT03635567.).
JCO
We report 5-year efficacy and safety outcomes from the phase III KEYNOTE-407 study (ClinicalTrials.gov identifier: NCT02775435). Eligible patients with previously untreated, metastatic squamous ...non-small-cell lung cancer (NSCLC) were randomly assigned 1:1 to pembrolizumab 200 mg or placebo plus carboplatin and paclitaxel/nab-paclitaxel once every 3 weeks for four cycles, followed by pembrolizumab or placebo for up to 35 cycles. Primary end points were overall survival (OS) and progression-free survival (PFS) per RECIST version 1.1 by blinded independent central review (BICR). Five hundred fifty-nine patients were randomly assigned in the intention-to-treat population (pembrolizumab plus chemotherapy, n = 278; placebo plus chemotherapy, n = 281). The median time from random assignment to data cutoff was 56.9 (range, 49.9-66.2) months. OS and PFS were improved with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (hazard ratio 95% CI, 0.71 0.59 to 0.85 and 0.62 0.52 to 0.74), with 5-year OS rates of 18.4% versus 9.7%, respectively. Toxicity was manageable. Among 55 patients who completed 35 cycles of pembrolizumab, the objective response rate was 90.9% and the 3-year OS rate after completion of 35 cycles (approximately 5 years after random assignment) was 69.5%. Pembrolizumab plus chemotherapy maintained an OS and PFS benefit versus placebo plus chemotherapy in previously untreated, metastatic squamous NSCLC and is a standard-of-care first-line treatment option for metastatic squamous NSCLC regardless of programmed death ligand 1 expression.
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