Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG).

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study.

In monarchE, adjuvant abemaciclib significantly improved invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS), with sustained benefit beyond the 2-year treatment period. Abemaciclib dose reductions were allowed to proactively manage adverse events. Exploratory analyses to investigate the impact of dose reductions on efficacy were conducted. Across the three patient subgroups as defined by relative dose intensity (≤66%, 66-93%, ≥93%), the estimated 4-year IDFS rates were generally consistent (87.1%, 86.4%, and 83.7%, respectively). In the time-dependent Cox proportional hazard model, the effect of abemaciclib was consistent at the full dose compared to being reduced to a lower dose (IDFS hazard ratio: 0.905; 95% confidence interval: 0.727, 1.125; DRFS hazard ratio: 0.942; 95% confidence interval: 0.742, 1.195). These analyses showed that the efficacy of adjuvant abemaciclib was not compromised by protocol mandated dose reductions for patients with node positive, hormone receptor positive, human epidermal growth factor 2-negative, high-risk early breast cancer.

Real-world treatment outcomes from nationwide Onco-colon Turkey registry in RAS wild-type patients treated with biologics second-line mCRC.

BACKGROUNDS AND OBJECTIVES: Colorectal cancer is one of the leading causes of mortality both globally and in our country. In Turkey, we conducted a multicenter investigation into the effectiveness of second-line treatments and real-life data for patients with RAS wild-type metastatic colorectal cancer (NCT04757311). MATERIALS AND METHODS: In this retrospective analysis, records from 28 centers were collected, and histopathological, molecular, and clinical characteristics were documented. Patients were categorized into groups based on their second-line biological treatments: anti-EGFR (Group A and Group B, panitumumab and cetuximab) and anti-VEGF (Group C, bevacizumab and aflibercept). They were then compared within these groups. RESULTS: A total of 588 patients with documented RAS wild-type status were evaluated. The median OS was 15.7, 14.3 and 14.7 months in Group A, Group B and Group C, respectively (p = 0.764). The median PFS of the patients in second-line setting that received panitumumab, cetuximab and bevacizumab/aflibercept were 7.8, 6.6 and 7.4 months, respectively (p = 0.848). CONCLUSION: According to the results of our real-life data study, there is no significant difference in efficiency between the combination of biological agent and chemotherapy used in the second-line treatments.

Adjuvant Abemaciclib Plus Endocrine Therapy for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, High-Risk Early Breast Cancer: Results From a Preplanned monarchE Overall Survival Interim Analysis, Including 5-Year Efficacy Outcomes.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Two years of adjuvant abemaciclib combined with endocrine therapy (ET) resulted in a significant improvement in invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) that persisted beyond the 2-year treatment period in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive, high-risk early breast cancer (EBC). Here, we report 5-year efficacy results from a prespecified overall survival (OS) interim analysis. In the intent-to-treat population, with a median follow-up of 54 months, the benefit of abemaciclib was sustained with hazard ratios of 0.680 (95% CI, 0.599 to 0.772) for IDFS and 0.675 (95% CI, 0.588 to 0.774) for DRFS. This persistence of abemaciclib benefit translated to continuous separation of the curves with a deepening in 5-year absolute improvement in IDFS and DRFS rates of 7.6% and 6.7%, respectively, compared with rates of 6% and 5.3% at 4 years and 4.8% and 4.1% at 3 years. With fewer deaths in the abemaciclib plus ET arm compared with the ET-alone arm (208 v 234), statistical significance was not reached for OS. No new safety signals were observed. In conclusion, abemaciclib plus ET continued to reduce the risk of developing invasive and distant disease recurrence beyond the completion of treatment. The increasing absolute improvement at 5 years is consistent with a carryover effect and further supports the use of abemaciclib in patients with high-risk EBC.

The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

A perspective: the integration of ctDNA into Response Evaluation Criteria in Solid Tumours 1.1 for phase II immunotherapy clinical trials.

A consensus guideline, iRECIST, was developed by the Response Evaluation Criteria in Solid Tumours (RECIST) working group for the use of the modified RECIST version 1.1 in cancer immunotherapy trials. iRECIST was designed to separate pseudoprogression from real progression. However, this is not the only ambiguous situation. In clinical immunotherapy trials, stable disease may reflect three tumor responses, including real stable disease, progressive disease and responsive disease. The prediction of a "true complete/partial response" is also important. Much data has accumulated showing that ctDNA can guide decisions at this point; thus, integrating ctDNA into the RECIST 1.1 criteria may help to distinguish a true tumor response type earlier in patients treated with immunotherapy; however, prospectively designed validation studies are needed.

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.

Efficacy and safety of the proposed bevacizumab biosimilar BAT1706 compared with reference bevacizumab in patients with advanced nonsquamous non-small cell lung cancer: A randomized, double-blind, phase III study.

BACKGROUND: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU-sourced reference bevacizumab (EU-bevacizumab) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). METHODS: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU-bevacizumab plus paclitaxel and carboplatin (EU-bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU-bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU-bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75-1.33 (China National Medical Products Administration requirements), or 0.73-1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of -0.12 to 0.15 (EMA requirements). RESULTS: In total, 649 randomized patients (BAT1706, n = 325; EU-bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU-bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94-1.24) and the ORR18 risk difference of 0.03 (95% CI: -0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU-bevacizumab. The safety profile of BAT1706 was consistent with that of EU-bevacizumab and no new safety signals were observed. CONCLUSION: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.

PNI as a Potential Add-On Biomarker to Improve the IMDC Intermediate Prognostic Score.

INTRODUCTION: This study aimed to assess the role of the adjusted PNI-IMDC risk scoring system in stratifying the intermediate group of metastatic RCC patients who received TKIS in the first-line setting. METHODS: A total of 185 patients were included. The adjusted PNI and IMDC model was used to divide the intermediate group into two groups: intermediate PNI-high and intermediate PNI-low groups. The statistical data were analyzed using Kaplan-Meier and Cox regression analysis. RESULTS: The results showed that the adjusted PNI-IMDC risk score, classic IMDC, and PNI had similar prognostic values. Adjusted PNI-IMDC risk score might be used for a more homogeneous differentiation of the classic intermediate group. On the other hand, multivariate analysis revealed that the presence of nephrectomy, adjusted favorable/intermediate (PNI-high) group, ECOG performance score, and presence of bone metastasis were independent predictors of OS. CONCLUSIONS: Pre-treatment PNI, as a valuable and potential add-on biomarker to the adjusted PNI-IMDC classification model, can be helpful for establishing an improved prognostic model for intermediate group mRCC patients treated with first-line TKISs. Further validation studies are needed to clarify these findings.

Molecular Pattern and Clinical Implications of KRAS/NRAS and BRAF Mutations in Colorectal Cancer.

The aim of our study was to evaluate the incidence of KRAS/NRAS and BRAF mutations, analyze molecular patterns, and investigate associations with clinical parameters of these mutations in CRC KRAS/NRAS and BRAF mutations analyzed by next-generation sequencing. The detection rates of these mutations and patients' demographics were recorded and the relationship between them was evaluated using the chi-square test. KRAS mutation was detected in 332 of 694 patients, while the mutation rates in KRAS exons 2/3 and 4 were 39.6%/3.2% and 5%, respectively. The most common mutation pattern was KRAS G12D. Five atypical variants were detected: V14I in KRAS exon 2, A18D, Q22K and T50I in exon 3, and T148P in exon 4. NRAS mutation was detected in 29 (4.5%) patients. One atypical variant L80W was detected in NRAS exon 3. BRAF mutation was seen in 37 (5.3%) patients, with BRAFV600E (83.8%) being the most common mutation pattern. NRAS mutation was significantly more frequent in patients > 64 years of age, BRAF mutation in women, and NRAS/BRAF mutations in right colon tumors. Grouping BRAF mutations into BRAFV600E and BRAFnon-V600E and their analysis according to specific tumor localizations showed that all four BRAFnon-V600E mutations originated in the rectum. In our study, KRAS exon 2 and other RAS mutation rates were higher than in the literature, while the BRAF v.600E mutation rate was similar. NRAS and BRAF mutations were significantly more frequent in the right colon. BRAF mutation was more common in women and in the right colon.

Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis.

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases. METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response. RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population. CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

Coexistence of Anti-PD1-Induced Immune Myocarditis and Complete Atrioventricular Block: A Case Report.

The present report describes the late recovery of an emerging complete atrioventricular (AV block) in a patient with immune check point inhibitor-related myocarditis following a period of immunosuppresive therapy. Therefore, decision-making for permanent pacemaker implantation should be implemented after a substantial period of time owing to the potential recovery of bradyarrhythmic complications in similar cases.

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.

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial.

INTRODUCTION: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-ßRII (a TGF-ß "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC. METHODS: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1-high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival. RESULTS: Patients (N = 304) were randomized one-to-one to receive either bintrafusp alfa or pembrolizumab (n = 152 each). The median follow-up was 14.3 months (95% confidence interval [CI]: 13.1-16.0 mo) for bintrafusp alfa and 14.5 months (95% CI: 13.1-15.9 mo) for pembrolizumab. Progression-free survival by independent review committee was not significantly different between bintrafusp alfa and pembrolizumab arms (median = 7.0 mo [95% CI: 4.2 mo-not reached (NR)] versus 11.1 mo [95% CI: 8.1 mo-NR]; hazard ratio = 1.232 [95% CI: 0.885-1.714]). The median overall survival was 21.1 months (95% CI: 21.1 mo-NR) for bintrafusp alfa and 22.1 months (95% CI: 20.4 mo-NR) for pembrolizumab (hazard ratio = 1.201 [95% CI: 0.796-1.811]). Treatment-related adverse events were higher with bintrafusp alfa versus pembrolizumab; grade 3-4 treatment-related adverse events occurred in 42.4% versus 13.2% of patients, respectively. The study was discontinued at an interim analysis as it was unlikely to meet the primary end point. CONCLUSIONS: First-line treatment with bintrafusp alfa did not exhibit superior efficacy compared with pembrolizumab in patients with PD-L1-high, advanced NSCLC.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

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.

Classifying invasive lobular carcinoma as special type breast cancer may be reducing its treatment success: A comparison of survival among invasive lobular carcinoma, invasive ductal carcinoma, and no-lobular special type breast cancer.

PURPOSE: The literature contains different information about the prognosis of invasive lobular carcinoma of breast cancer (BC). We aimed to address the inconsistency by comparatively examining the clinical features and prognosis of invasive lobular carcinoma patients in our university and to report our experience by dividing our patients into various subgroups. PATIENTS AND METHODS: Records of patients with BC admitted to Trakya University School of Medicine Department of Oncology between July 1999 and December 2021 were reviewed. The patients were divided into three groups (No-Special Type BC, Invasive Lobular Special Type BC, No-Lobular Special Type BC). Patient characteristics, treatment methods and oncological results are presented. Survival curves were generated using the Kaplan-Meier method. Statistical significance of survival among the selected variables was compared by using the log-rank test. RESULTS: The patients in our study consisted of 2142 female and 15 male BC patients. There were 1814 patients with No-Special Type BC, 193 patients with Invasive Lobular Special Type BC, and 150 patients with No-Lobular Special Type BC. The duration of disease-free survival (DFS) was 226.5 months for the No-Special Type BC group, 216.7 months for the No-Lobular Special Type BC group, and 197.2 months for the Invasive Lobular Special Type BC group, whereas the duration of overall survival (OS) was 233.2 months for the No-Special Type BC group, 227.9 for the No-Lobular Special Type BC group, and 209.8 for the Invasive Lobular Special Type BC group. The duration of both DFS and OS was the lowest in the Invasive Lobular Special Type BC group. Multivariate factors that were significant risk factors for OS were Invasive Lobular Special Type BC histopathology (p = .045), T stage, N stage, stage, skin infiltration, positive surgical margins, high histological grade, and mitotic index. Modified radical mastectomy, chemotherapy, radiotherapy and use of tamoxifen and aromatase inhibitors for more than 5 years were significant protective factors for overall survival. CONCLUSION: The histopathological subgroup with the worst prognosis in our study was Invasive Lobular Special Type BC. Duration of DFS and OS were significantly shorter in Invasive Lobular Special Type BC than No-Lobular Special Type BC group. The classification of Invasive Lobular BC under the title of Special Type BC should be reconsidered and a more accurate treatment and follow-up process may be required.

Relationship between prognostic nutritional index and neutrophil lymphocyte ratio with overall survival in patients with metastatic colorectal cancer receiving regorafenib.

Aim: In this study, we aimed to analyze the effect of prognostic nutritional index and neutrophile lymphocyte ratio on the overall survival (OS) in patients treated with regorafenib. Materials and Methods: Metastatic colorectal cancer (CRC) patients who treated with regorafenib between 2016 and 2020 in a single center were evaluated retrospectively. ROC analysis was used for neutrophile lymphocyte ratio (NLR's) and prognostic nutritional index (PNI's) optimum cut-off value. The relationship between OS with PNI and NLR was investigated. Results: Fifty-two patient's data were analyzed. The median age was 57 years, 22 (41.5%) of the patients were female. The optimal cut-off value of PNI for OS was 45.7 according to ROC curve analysis. The median NLR value was accepted as 2.7. Median OS was 8.3 months. Patients who have high PNI value than 45.7 had longer OS (12.09 months vs. 6.31 months hazard ratio [HR]: 0.37 95% confidence interval [CI]: 0.19-0.73 P = 0.003) and there was a tendency for longer OS with low NLR value then median (12.05 months vs. 6.14 months HR: 0.54 95% CI: 0.29-1.23 P = 0.057). Primary tumor resected patients had longer OS than nonresected patients (12.05 months vs. 6.30 months HR: 0.34 95% CI: 0.17-0.66 P = 0.001). In multivariate analysis, high PNI value more than 45.7 (HR: 0.40 95% CI: 0.18-0.88 P = 0.02) and resection of the primary tumor (HR: 0.40 95% CI: 0.21-0.80 P = 0.01) were the only independent factors for longer OS. Conclusion: Metastatic CRC patients with high pretreatment PNI and primary tumor resected are more likely to have longer OS with regorafenib. PNI is more reliable index than NLR to predict OS in metastatic CRC patients treated with regorafenib.

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study.

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.

Lazertinib Versus Gefitinib as First-Line Treatment in Patients With EGFR-Mutated Advanced Non-Small-Cell Lung Cancer: Results From LASER301.

PURPOSE: Lazertinib is a potent, CNS-penetrant, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. This global, phase III study (LASER301) compared lazertinib versus gefitinib in treatment-naïve patients with EGFR-mutated (exon 19 deletion [ex19del]/L858R) locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were 18 years and older with no previous systemic anticancer therapy. Neurologically stable patients with CNS metastases were allowed. Patients were randomly assigned 1:1 to lazertinib 240 mg once daily orally or gefitinib 250 mg once daily orally, stratified by mutation status and race. The primary end point was investigator-assessed progression-free survival (PFS) by RECIST v1.1. RESULTS: Overall, 393 patients received double-blind study treatment across 96 sites in 13 countries. Median PFS was significantly longer with lazertinib than with gefitinib (20.6 v 9.7 months; hazard ratio [HR], 0.45; 95% CI, 0.34 to 0.58; P < .001). The PFS benefit of lazertinib over gefitinib was consistent across all predefined subgroups. The objective response rate was 76% in both groups (odds ratio, 0.99; 95% CI, 0.62 to 1.59). Median duration of response was 19.4 months (95% CI, 16.6 to 24.9) with lazertinib versus 8.3 months (95% CI, 6.9 to 10.9) with gefitinib. Overall survival data were immature at the interim analysis (29% maturity). The 18-month survival rate was 80% with lazertinib and 72% with gefitinib (HR, 0.74; 95% CI, 0.51 to 1.08; P = .116). Observed safety of both treatments was consistent with their previously reported safety profiles. CONCLUSION: Lazertinib demonstrated significant efficacy improvement compared with gefitinib in the first-line treatment of EGFR-mutated advanced NSCLC, with a manageable safety profile.