Genetic testing and counseling challenges in personalized breast cancer care: review article with insights from Türkiye.

According to current evidence, testing for germline BRCA pathogenic variants in newly diagnosed breast cancer (BC) patients has the potential to reduce the burden of the disease through targeted therapies and secondary prevention. A personalized approach to testing can lead to improved individual outcomes for patients. Despite the proven clinical utility and therapeutic impact of BRCA1/2 tests in shaping therapy for metastatic BC, awareness and access to these tests are limited in many developing countries, including Türkiye. This limitation impacts the healthcare economy as delayed or missed interventions can lead to increased long-term costs. The limited access is mainly due to fear of stigmatization among patients, country-specific legislation and costs, a lack of awareness, vagueness surrounding the tests and access restrictions. This review offers a perspective for policymakers and healthcare providers in Türkiye to establish pathways that integrate the patient experience into comprehensive care pathways and national cancer control plans.

Recent studies show that testing for a specific gene change in people newly diagnosed with breast cancer can help reduce the impact the disease has on their life as they can be given special treatments. When tests are tailored to each person, they can get better results. However, in many countries, including Türkiye, not many people know about or can get these tests. This is because of concerns about being judged, rules in the country, the cost, confusion about the tests and limited access. Not having these tests can make healthcare more expensive in the long run. This article suggests ways for Türkiye's leaders and health workers to make these tests a regular part of cancer care and planning.

Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors.

PURPOSE: This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). METHODS: In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023. RESULTS: Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001). CONCLUSIONS: Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression. METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540. FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Immunogenicity of two doses of inactive COVID-19 vaccine and third booster dose mRNA vaccine in patients with cancer receiving active systemic therapy.

We aimed to evaluate the seroconversion rates after two doses of inactive COVID-19 vaccine (CoronaVac) and the benefit of a third dose mRNA vaccine booster in patients with cancer receiving active treatment. Patients with solid tumors receiving active treatment (n = 101) and patients with no-cancer (n = 48) as the control group were included in the study. All the patients and controls had received two doses of CoronaVac and a third booster dose of the mRNA vaccine (Bnt162b2). Anti-SARS-CoV-2 Spike Receptor Binding Domain IgG antibody levels after the second and third dose were measured with quantitative ELISA. The median age of the patients was 66 (IQR 60-71). 79% of the patients were receiving chemotherapy, and 21% were receiving immunotherapy at the time of vaccination. Antibody levels measured after two doses of CoronaVac were significantly lower in patients with cancer than in the control group (median 0 µg/ml [IQR 0-1.17 µg/ml] vs median 0.91 µg/ml [IQR 0-2.24 µg/ml], respectively, P = .002). Seropositivity rates were 46.5% in patients with cancer and 72.9% in the control group (P = .002). Antibody measurement was performed in 26 patients after the third dose. Seroconversion rate increased from 46.5% to 88.5% (P < .001), and the antibody titers significantly increased with the third-dose booster (median 0 µg/ml [IQR 0-1.17 µg/ml] after two doses vs 12.6 µg/ml [IQR 1.8-69.1 µg/ml] after third booster dose, P < .001). Immunogenicity of CoronaVac is low in patients with cancer receiving active treatment, and administering a third dose of an mRNA vaccine is effective in terms of improving seroconversion rates.

Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of ≥50%: The EMPOWER-Lung 1 study.

BACKGROUND: In the EMPOWER-Lung 1 trial (ClinicalTrials.gov, NCT03088540), cemiplimab conferred longer survival than platinum-doublet chemotherapy for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) ≥50%. Patient-reported outcomes were evaluated among trial participants. METHODS: Adults with NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1 were randomly assigned cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. At baseline and day 1 of each treatment cycle, patients were administered the European Organization for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Lung Cancer Module (QLQ-LC13) questionnaires. Mixed-model repeated measures analysis estimated overall change from baseline for PD-L1 ≥50% and intention-to-treat populations. Kaplan-Meier analysis estimated time to definitive deterioration. RESULTS: In PD-L1 ≥50% patients (cemiplimab, n = 283; chemotherapy, n = 280), baseline QLQ-C30 and QLQ-LC13 scores showed moderate-to-high functioning and low symptom burden. Change from baseline favored cemiplimab on global health status/quality of life (GHS/QOL), functioning, and most symptom scales. Risk of definitive deterioration across functioning scales was reduced versus chemotherapy; hazard ratios were 0.48 (95% CI, 0.32-0.71) to 0.63 (95% CI, 0.41-0.96). Cemiplimab showed lower risk of definitive deterioration for disease-related (dyspnea, cough, pain in chest, pain in other body parts, fatigue) and treatment-related symptoms (peripheral neuropathy, alopecia, nausea/vomiting, appetite loss, constipation, diarrhea) (nominal p < .05). Results were similar in the intention-to-treat population. CONCLUSIONS: Results support cemiplimab for first-line therapy of advanced NSCLC from the patient's perspective. Improved survival is accompanied by improvements versus platinum-doublet chemotherapy in GHS/QOL and functioning and reduction in symptom burden.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510-7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225-6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017-4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923-4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947-4.327; P = 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.

Safety of lorlatinib in ALK-positive non-small-cell lung cancer and management of central nervous system adverse events.

The use of tyrosine kinase inhibitors has made a breakthrough in the treatment of non-small-cell lung cancer (NSCLC). Recently, lorlatinib, a third-generation tyrosine kinase inhibitor, has demonstrated significant systemic and intracranial activity in both first-line and subsequent-line therapy in ALK-positive NSCLC patients. In this review, general characteristics of lorlatinib, its efficacy in the treatment of ALK-positive NSCLC patients and the safety of lorlatinib, particularly addressing central nervous system adverse events, are discussed. Management of central nervous system adverse events, which seem to be specific to lorlatinib therapy, is outlined.

Lung cancer is a common disease and affects patients badly. Lorlatinib is a new and useful drug for this disease. But this drug has also some undesirable effects for the brain. These effects are generally mild and can be treated. This article discusses the undesirable effects of this drug on the brain and how to cope with these effects.

Impact of pharmacist-led educational intervention on pneumococcal vaccination rates in cancer patients: a randomized controlled study.

PURPOSE: This study aimed to evaluate clinical pharmacist's contribution to the pneumococcal vaccination rate by providing education to cancer patients in hospital settings. METHODS: This study was conducted in 2 tertiary-care hospitals' medical oncology outpatient clinics. Patients over 18 years of age and diagnosed with cancer for less than 2 years, in remission stage, and have not previously received the pneumococcal vaccine were included. Patients were randomized to intervention and control groups. The intervention group was provided vaccination education and recommended to receive the PCV13 vaccine. The control group received routine care. Patients' knowledge about pneumonia/pneumococcal vaccine, Vaccine Attitude Examination Scale (VAX) score, and vaccination rates were evaluated at baseline and 3 months after the education. RESULTS: A total of 235 patients (intervention: 117, control: 118) were included. The mean age ± SD was 57.86 ± 11.88 years in the control and 60.68 ± 11.18 years in the intervention groups. The numbers of correct answers about pneumonia/pneumococcal vaccine (p = 0.482) and VAX scores (p = 0.244) of the groups were similar at baseline. After the intervention, the median (IQR) number of correct answers in intervention group [10(3)] was higher than control group [8(4)] (p < 0.001). After the education, the total VAX score (mean ± SD) was less in intervention group (33.09 ± 7.018) than the control group (36.07 ± 6.548) (p = 0.007). Three months after the education, 20.2% of the patients in the intervention and 6.1% in the control groups were vaccinated with pneumococcal vaccine (p = 0.003). CONCLUSIONS: The pneumococcal vaccination rate in cancer patients has increased significantly by the education provided by a clinical pharmacist in hospital settings.

Immune checkpoint inhibitor-related hearing loss: a systematic review and analysis of individual patient data.

PURPOSE: Immune checkpoint inhibitors (ICIs) are related to various immune-related adverse events (irAEs). However, the knowledge is limited with rare irAEs like hearing loss. Therefore, we evaluated the characteristics, presentation, and treatment of ICI-related hearing loss by reviewing the individual patient data from the previous studies. METHODS: We conducted a systematic search of the Web of Science, PubMed, and Embase databases for studies published until 17 November 2022. The selected MeSH search terms were "hearing loss" OR "hearing impairment" OR "ototoxicity" OR "vestibular toxicity" OR "audiovestibular toxicity" AND "immune checkpoint inhibitor" OR "immunotherapy." RESULTS: A total of 38 patients were included. Melanoma was the most frequent diagnosis (73.7%). The median time from ICI initiation to hearing loss development was 3 months. The hearing impairment was secondary to bilateral sensorineural hearing loss (SNHL) in 24 (68.6%) patients, and at least one other irAE accompanied the hearing loss in 24 patients. Hearing loss significantly improved in 45.7% of the patients. The overall response rate and disease control rate were 67.6% and 85.3%, respectively. CONCLUSION: We observed that most cases of ICI-related hearing loss were reversible, observed in patients with melanoma, accompanied by other irAEs, and associated with a high response rate to ICIs. With the expanded use of ICIs in the earlier treatment lines and adjuvant settings, the number of survivors with ICI-related hearing loss is expected to increase. Further research is needed to define the true prevalence of ICI-related hearing loss, optimal diagnosis, and management.

Intracerebral de novo arterio-venous malformations as a side effect of bevacizumab.

INTRODUCTION: Bevacizumab is a monoclonal antibody for the vascular endothelial growth factor receptor and is utilized in the treatment of various tumors. Gastrointestinal perforation/fistula, heart failure, hemorrhage, hypertension, proteinuria/nephrotic syndrome, thromboembolism, posterior reversible encephalopathy syndrome, and necrotizing fasciitis are serious side effects of bevacizumab. Bevacizumab associated de novo brain arterio-venous malformation formation has not been documented in the literature. CASE REPORT: Here, we presented a 35-year-old female patient with recurrent high-grade glial tumor who developed multiple supra- and infratentorial de novo arterio-venous malformations after receiving the last dose of bevacizumab. MANAGEMENT & OUTCOME: Intervention options for the adverse effect were limited. In fact, there was no chance of intervention because the patient died for another reason. DISCUSSION: Based on this experience, it can be hypothesized that bevacizumab may induce de novo arterio-venous malformations in the brain as a result of arterial and venous thrombotic effects. Additional studies should be done to clarify the causal relationship between bevacizumab and arterio-venous malformations in primary brain tumors.

Clinical Features and Prognostic Factors of Metastatic Non-Clear Cell Renal Cell Carcinoma: A Multicenter Study from the Turkish Oncology Group Kidney Cancer Consortium.

INTRODUCTION: We aimed to evaluate clinical features, prognostic factors, and treatment preferences in patients with non-clear cell renal cell carcinoma (nccRCC). METHODS: Patients with metastatic nccRCC were selected from the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database. Clinical features, prognostic factors, and overall survival (OS) outcomes were investigated. RESULTS: A total of 118 patients diagnosed with nccRCC were included in this study. The median age at diagnosis was 62 years (interquartile range: 56-69). Papillary (57.6%) and chromophobe tumors (12.7%) are common histologic subtypes. Sarcomatoid differentiation was present in 19.5% of all patients. When the patients were categorized according to the International Metastatic RCC Database Consortium (IMDC) risk scores, 66.9% of the patients were found to be in the intermediate or poor risk group. Approximately half of the patients (55.9%) received interferon in the first line. At the median follow-up of 53.2 months (95% confidence interval [CI]: 34.7-71.8), the median OS was 19.3 months (95% CI: 14.1-24.5). In multivariate analysis, lung metastasis (hazard ratio [HR]:2.22, 95% CI: 1.23-3.99) and IMDC risk score (HR: 2.35, 95% CI: 1.01-5.44 for intermediate risk; HR: 8.86, 95% CI: 3.47-22.61 for poor risk) were found to be independent prognostic factors. CONCLUSION: In this study, survival outcomes are consistent with previous studies. The IMDC risk score and lung metastasis are the independent prognostic factors for OS. This is an area that needs research to better treat this group of patients and create new treatment options.

Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial.

BACKGROUND: 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%. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Pazopanib-induced chylothorax in a patient with renal cell carcinoma.

Pazopanib is an oral multi-kinase inhibitor approved for the treatment of advanced renal cell carcinoma (RCC). It is an anti-angiogenic agent, which blocks the activation signaling pathways of tyrosine kinases and prevents the activities of primarily vascular endothelial growth factor receptors (VEGFR)-2 and VEGFR-3, which are important in lymphangiogenesis. Herein, we report a patient with advanced RCC who developed asymptomatic left-sided chylothorax under pazopanib therapy. Chylothorax developed in the 16th month and gradually increased until it was diagnosed by thoracentesis in the 22nd month. The development of chylothorax was attributed to pazopanib therapy after ruling out all possible traumatic and nontraumatic etiologies. The 'Adverse Drug Reaction Probability Scale' revealed a total score of 6, which fell into 'probable' category. Chylothorax regressed significantly 5 weeks after the discontinuation of pazopanib therapy.

Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study.

AIM: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib. METHODS: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients. RESULTS: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group. CONCLUSION: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Response to first-line chemotherapy regimen is associated with efficacy of immune checkpoint blockade therapies in patients with metastatic urothelial carcinoma.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important. PATIENTS AND METHODS: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher's exact test. Median follow-up was calculated using the reverse Kaplan-Meier method. OS was estimated by using the Kaplan-Meier method. RESULTS: The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (p = 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (p = 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio [HR] = 1.9; p = 0.04}, ECOG PS ≥ 1 (HR = 2.7; p = 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8; p < 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39; p < 0.001) maintained a significant association with OS in multivariate analysis. CONCLUSIONS: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients' use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

Oncologists' attitudes towards prophylaxis of cancer associated venous thromboembolism: A prospective, descriptive study.

INTRODUCTION: Cancer-associated venous thromboembolism creates a big burden on both patients and healthcare systems. Clinical guidelines have a consensus on the initiation of prophylactic treatment for hospitalised patients, however a debate still exists for ambulatory cancer patients. Therefore, this study aimed to identify attitudes and practices of medical oncologists on cancer-associated venous thromboembolism management. METHODS: An online survey consisting of 22 questions was developed by researchers in the view of previous studies and delivered to 100 medical oncologists registered to the national society of medical oncology by e-mail between September and October 2018. Descriptive and statistical analyses were performed using Statistical Package for Social Science (SPSS) version 23.0 (ICM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp). RESULTS: A total of 62 medical oncologists (75.8% male) responded to the survey (response rate of 62%). The most critical three risk factors considered for initiating prophylaxis were prior venous thromboembolism history, immobilisation and tumour/cancer type for inpatients and outpatients (χ2 test, p < 0.001). The first choice of drug for prophylaxis was mostly low molecular weight heparins (n = 60, 96.8%). In the absence of contraindications, physicians initiate prophylaxis 'usually' for inpatients (n = 25, 40.3%) and outpatients (n = 5, 8.1%). However routine use of the Khorana score is not incorporated into the risk assessment process of cancer patients. CONCLUSION: Attitudes of oncologists towards thromboprophylaxis in cancer patients are consistent with previous studies in the literature. The respondents are aware of the venous thromboembolism risk of cancer patients, however raising awareness on both cancer-associated venous thromboembolism and current guideline recommendations is needed.

The burden of polypharmacy and drug-drug interactions in older cancer patients treated with immunotherapy.

INTRODUCTION: Polypharmacy is a common problem in older cancer patients, although the data about polypharmacy and potentially inappropriate prescription practices is limited in patients treated with immune checkpoint inhibitors (ICIs). Therefore, we aimed to evaluate the polypharmacy frequency and drug-drug interactions in older cancer patients (≥65 years) treated with ICIs. METHODS: A total of 70 geriatric patients with advanced cancer were included. The polypharmacy was defined as regular use of 5 or more drugs. The START/STOPP Criteria Version 2 was used for the potentially inappropriate medications (PIM) and potential prescription omissions (PPO). The Medscape Drug Interaction Checker was used for potential drug-drug interactions. RESULTS: The patients had a median of 6 regular drugs, and polypharmacy was present in 77.1%. The polypharmacy risk was significantly increased in patients over 75 years of age (p = 0.028) and with opioid use (p = 0.048). The 50% of patients had category D or X interactions. Patients with higher Charlson Comorbidity Index had significantly increased risk for drug interactions (CCI ≤10 vs. >10, p = 0.017). The PIMs were present in 44.3% and the PPOs in 68.6% of the patients. While the overall survival and immune related adverse events were similar according to polypharmacy, in patients using seven or more drugs, the acute kidney injury risk was increased (HR: 4.667, p = 0.038). CONCLUSION: In this study, we observed a high rate of polypharmacy and inappropriate prescription practices in ICI-treated patients. These issues pointed out the need for improved general medical care and attention for better comedication management in ICI-treated patients.

Clinical features and outcomes of COVID-19 in patients with solid tumors: Turkish National Registry Data.

We present demographic, clinical, laboratory characteristics and outcomes of the patients with solid malignancies and novel coronavirus disease (COVID-19) collected from the National COVID-19 Registry of Turkey. A total of 1523 patients with a current or past diagnosis of solid tumors and diagnosed with COVID-19 (confirmed with PCR) between 11 March and 20 May 2020 were included. The primary outcome was 30-day mortality. Median age was 61 (range: 18-94), and 752 (49%) were male. The most common types of cancers were breast (19.8%), prostate (10.9%) and colorectal cancer (10.8%). 65% of the patients had at least one comorbidity. At least one COVID-19-directed therapy was given in 73% of the patients.. Hospitalization rate of the patients was 56.6% and intensive care unit admission rate was 11.4%. Seventy-seven (5.1%) patients died within 30 days of diagnosis. The first multivariate model which included only the demographic and clinical characteristics showed older age, male gender and presence of diabetes and receipt of cytotoxic therapy to be associated with increased 30-day mortality, while breast and prostate cancer diagnoses were associated with lower 30-day mortality. In the second set, we further included laboratory parameters. The presence of leukocytosis (OR 6.7, 95% CI 3.3-13.7, P < .001), lymphocytopenia (OR 3,1, 95% CI 1,6-6,1, P = .001) and thrombocytopenia (OR 3,4 95% CI 1,5-8,1, P = .005) were found to be associated with increased 30-day mortality. Relatively lower mortality compared to Western countries and China mainly results from differences in baseline risk factors but may also implicate the importance of intensive supportive care.