Efficacy of first-line CDK 4-6 inhibitors in premenopausal patients with metastatic breast cancer and the effect of dose reduction due to treatment-related neutropenia on efficacy: a Turkish Oncology Group (TOG) study.

The only phase 3 study on the effectiveness of CDK 4-6 inhibitors in first-line treatment in premenopausal patients with hormone receptor (HR) positive, HER2 negative metastatic breast cancer is the MONALEESA-7 study, and data on the effectiveness of palbociclib is limited. Data are also limited regarding the effectiveness of CDK 4-6 inhibitors in patients whose dose was reduced due to neutropenia, the most common side effect of CDK 4-6 inhibitors. In our study, we aimed to evaluate the effectiveness of palbociclib and ribociclib in first-line treatment in patients with premenopausal metastatic breast cancer and the effect of dose reduction due to neutropenia on progression-free survival. Our study is a multicenter, retrospective study, and factors affecting progression-free survival (PFS) were examined in patients diagnosed with metastatic premenopausal breast cancer from 29 different centers and receiving combination therapy containing palbociclib or ribociclib in the metastatic stage. 319 patients were included in the study. The mPFS for patients treated with palbociclib was 26.83 months, and for those receiving ribociclib, the mPFS was 29.86 months (p = 0.924). mPFS was 32.00 months in patients who received a reduced dose, and mPFS was 25.96 months in patients who could take the initial dose, and there was no statistical difference (p = 0.238). Liver metastasis, using a fulvestrant together with a CDK 4-6 inhibitor, ECOG PS 1 was found to be a negative prognostic factor. No new adverse events were observed. In our study, we found PFS over 27 months in patients diagnosed with premenopausal breast cancer with CDK 4-6 inhibitors used in first-line treatment, similar to post-menopausal patients. We did not detect any difference between the effectiveness of the two CDK 4-6 inhibitors, and we showed that there was no decrease in the effectiveness of the CDK 4-6 inhibitor in patients whose dose was reduced due to neutropenia.

Comparison of the Efficiency of Induction and Adjuvant Chemotherapy in Patients with Locally Advanced Nasopharyngeal Cancer.

OBJECTIVE: To make a comparative evaluation of induction chemotherapy (ICT) or adjuvant chemotherapy (ACT) added to standard concurrent chemoradiotherapy in patients diagnosed with locally advanced nasopharyngeal cancer (LANPC) (Stage 3-4a patients, except T3N0). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from April 2009 to June 2021. METHODOLOGY: Clinicopathological features of adult patients diagnosed with LANPC were recorded from the hospital's patient registry database. Patients without the medical records were excluded. An assessment of the effectiveness of induction or ACT added to standard definitive chemoradiotherapy (CRT) was performed, and the application cycles were evaluated. RESULTS: Seventy-four patients (71.6% male, mean age 50.8±11.7) with LANPC were included in the study. There is no statistical difference in progression-free survival (PFS) between patients who applied ICT (before CRT) and ACT (after CRT) (p = 0.61). Female patients and patients aged ≤50 years had better PFS as independent factors (HR=3.82, 95% CI 1.14-12.74, p = 0.029; HR: 1.06 95% CI 1.02-1.10, p = 0.002, respectively). Also, patients aged 50 years and younger and female patients had a statistically longer overall survival (OS) (p = 0.045, and p = 0.012, respectively). While there was statistically no significant difference in PFS according to the number of cycles for EBER-positive patients received adjuvant Cisplatin-5FU (CF); 3 cycles compared to 2 showed a statistically higher OS (p = 0.06, and p = 0.022, respectively).     Conclusion: LANPC patients were found to have a positive survival if they were young and females. There was a positive impact on survival of intensified adjuvant CF in EBER-positive nonkeratinising, undifferentiated LANPC patients. KEY WORDS: Locally advanced nasopharyngeal cancer, EBER, Induction chemotherapy, Adjuvant chemotherapy.

Efficacy and Safety of Combined Chemotherapy Regimens with Bevacizumab in Platinum-sensitive Ovarian Cancers.

OBJECTIVE: To determine the differences in terms of overall survival in platinum-sensitive ovarian cancer (PSOC) patients undergoing various chemotherapy protocols, and to demonstrate patient tolerance, toxicity, and efficacy data with the use of bevacizumab in different protocols. STUDY DESIGN: An observational study. Place and Duration of the Study: Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from January 2018 to January 2022. METHODOLOGY:  Patients aged 18 and above, who had received treatment for PSOC, were included in the study. Patients with platinum-resistant disease and those for whom bevacizumab usage was contraindicated were not enrolled in the study. RESULTS: For the 95 patients, the median age was 55 (34-78) years. Median follow-up are 39.7 (39.2-47.5) months. Median progression-free survival (PFS) of the patients are 10.8 (7.3-14.0) months for carboplatin-gemcitabine-bevacizumab (CGB), 10.9 (IQR 5.5-14.3) months in the carboplatin-liposomal doxorubicin-bevacizumab (CLdB) arms, and 6.1 (IQR 5.8-14.3) months in the carboplatin-paclitaxel-bevacizumab (CPB) group (p=0.79). The median overall survivals (OS) are 37.9 (IQR 33.3-46.9) months in the CGB arm, 41.0 (IQR 38.0-50.3) months CPB arm, and 41.3 (IQR 38.1-52.3) months in the CLdB arm (p=0.173). CONCLUSION: There was no difference in terms of overall survival among all three chemotherapy protocols. However, due to the difference in toxicity, the treatment should be selected on a patient-specific basis. Additionally, the use of bevacizumab at a dose of 7.5 mg/kg was demonstrated to be equivalent to using 15 mg/kg in terms of overall survival. This lower dose is also important to avoid financial toxicity. KEY WORDS: Bevacizumab, Ovarian cancer, Platinum-based chemotherapy, Tolerability, Adverse clinical events.

Prognostic Importance of Combined Use of MELD Scores and SII in Hepatic Visceral Crisis in Patients with Solid Tumours.

OBJECTIVE: To determine the sensitivity of combining the model for end-stage liver disease (MELD) scoring with new inflammatory indexes in determining the priority for liver transplantation and demonstrating its potential usability in solid tumour visceral crisis. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkiye, from June 2017 to June 2022. METHODOLOGY:  Patients hospitalised in the medical oncology clinic for hepatic dysfunction were included. The MELD scores of these patients were calculated, and the predictive contribution of the systemic immune-inflammatory index (SII) to prognosis and mortality was evaluated. RESULTS: A total of 295 patients (158 (53.6%) men and 137 (46.4%) women) were included. When compared for primary tumour types, colorectal cancers were the most common with 55 (18.6%) cases, followed by breast cancers at 52 (17.6%), pancreatic carcinoma at 50 (16.9%), and stomach cancers at 40 (13.6%) cases. In the survival analyses of all three MELD scores (MELD-Original, MELD-Na, and MELD 3.0) between <20 groups and ≥20 groups, the median Overall Survival (OS) for MELD-Original was 1.44 vs. 0.88 months (p<0.001), for MELD- Na it was 1.64 vs. 0.85 months (p<0.001), and for MELD 3.0 it was 2.16 vs. 1.28 months (p=0.039). In the ROC analysis, the SII parameter cut-off was ≥626.28 for the estimation of mortality, SII sensitivity was 78.7%, and specificity was 100% (p=0.013). CONCLUSION: Combined use of MELD and SII scores in patients with solid tumours with hepatic visceral crises will be practical, cost-effective, and easy to access, eliminate gender-based disparities, and contribute to clinical follow-ups with objective data. KEY WORDS: Malignant neoplasm, MELD score, MELD-Na, MELD 3.0, SII.

Prognostic Markers after Hepatic Function Impairment in Patients with Pancreatic Adenocarcinoma.

OBJECTIVE: To determine the factors affecting survival after hepatic failure in patients with pancreatic adenocarcinoma (PAC) who developed hepatic dysfunction accompanied by hyperbilirubinemia. STUDY DESIGN: Observational Study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey, from January 2017 to May 2022. METHODOLOGY: The clinical characteristics of adult patients who developed hepatic dysfunction accompanied by hyperbilirubinemia with a diagnosis of PAC and died in their follow-up were recorded from the hospital's patient registry database. Patients without medical record were excluded. The effective parameters of overall survival after hepatic failure (aHFOS) were determined. RESULTS: The study included 57 patients with PAC (56.1% males) who developed hepatic dysfunction during their follow-up. According to the CA 19-9 value at the time of diagnosis, the tumour localisation was predicted to be located in the head and neck (Cutoff ≤1400, AUC 0.77, sensitivity 73.2%, specificity 75%; p=0.002). Values of international normalised ratio (INR, p=0.010), blood urea nitrogen (BUN, p=0.002) that were measured during hepatic dysfunction, and tumour location in the head and neck in the pancreas (p=0.028) were determined as independent variables affecting aHFOS in patients with PAC. In addition, percutaneous transhepatic biliary drainage (PTDB) application during liver failure and initiation of chemotherapy in appropriate patients also positively affected aHFOS (2.62 months vs. 0.92 months, p=0.016 and 3.45 months vs. 1.11 months, p=0.003; respectively). CONCLUSION: Sufficient liver function reserve in malignant patients is highly effective in the curability and survival of patients. In this regard, it is crucial to improve prognosis by identifying the factors affecting aHFOS in patients with PAC who develop hepatic dysfunction due to liver metastasis or the primary tumour characteristics. KEY WORDS: Pancreatic adenocarcinoma, CA 19-9, Hepatic failure, Prognosis, Survival.

Experiences of the combined use of Favipiravir in patients using Lorlatinib and Brigatinib.

INTRODUCTION: The SARS-COV-2 (COVID-19) pandemic is challenging the management of cancer patients. In this article, we present two patients diagnosed with anaplastic lymphoma kinase (ALK) + non-small cell lung adenocarcinoma (NSCL CA), infected with COVID-19, who had a previous multi-line therapy with Brigatinib and Lorlatinib, and received Favipiravir for their current infection. CASE REPORTS: A 58-year-old man and a 65-year-old woman were diagnosed as ALK ( + ) NSCL CA. Both patients received tyrosine kinase inhibitors (TKI) for lung cancer when diagnosed with COVID-19. No adverse effects were observed with the concurrent use of Favipiravir, an antiviral drug currently used for COVID-19 and TKI. MANAGEMENT AND OUTCOME: Considering the pharmacokinetic effects of favipiravir and the ALK inhibitor TKI's used on our cases (Brigatinib-Lorlatinib), the concurrent use of these drugs was safe and prevented the delay in the primary treatment of the malignancy of our patients. DISCUSSION: To our knowledge, these are the only reported cases diagnosed as ALK ( + ) NSCL CA who received favipiravir because of COVID-19 while using TKI, and both patients recovered completely without any side effects.