Real-world evaluation of nivolumab in patients with non-nasopharyngeal recurrent or metastatic head and neck cancer: a retrospective multi-center study by the Turkish Oncology Group (TOG).

OBJECTIVES: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. DESIGN: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. RESULTS: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4-15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. CONCLUSIONS: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes.

Effect of HER2/CEP17 ratio on survival in metastatic HER2-positive gastric cancer, multicenter study.

AIM: HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer. METHODS: A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed. RESULTS: The median age was 64 (24-83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36-27.58), and in the low ratio group was 16.17 months (95% CI: 10.95-21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02-28.37) in the high HER2 gene copy number group and 10.13 months (5.55-14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55-14.33) in the group with high HER2 gene copy number and 7.56 months (4.62-10.49) in the low copy number group (p = 0.06). CONCLUSION: Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.

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.