Introduction: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors are the new generation drugs that have been started to be used in our clinical practice recently. These drugs have been shown to have better progression-free survival compared to standard therapy in patients with hormone receptor-positive (HR) and human epidermal growth factor receptor 2 (HER-2)-negative breast cancer. The most common side effects of CDK 4-6 inhibitors are neutropenia, nausea, leukopenia, fatigue, and diarrhea. This case demonstrated vortex keratopathy in both eyes, a rare condition in patients with breast cancer treated with ribociclib. Case report: A 68-year-old female patient was diagnosed with locally advanced HR (+)/HER2 (−) breast cancer in March 2015. In June 2021, bone metastases were detected. The patient was started on ribociclib and fulvestrant. After three cycles of ribociclib and fulvestrant treatment, she was admitted with the complaint of blurred vision in her left eye. Slit-lamp biomicroscopy examination revealed subepithelial haze with central subepithelial whorls in both corneas, more in the left eye, and also a mild punctate epithelial staining was observed with the application of fluorescein dye. Management and outcome: Ribociclib treatment was immediately discontinued and no changes were observed in the cornea and vision levels during the one-month follow-up. Discussion: Routine and regular follow-up eye examinations in breast cancer patients treated with ribociclib may benefit patients in our daily clinical practice and may help us to detect side effects at an early stage and to manage them more effectively.

Background: Non-small cell lung cancer (NSCLC) is often diagnosed late with many patients (pts) not responding to first line therapy or only responding for a limited time. BNT116 is an intravenously administered uridine RNA-based lipoplex cancer vaccine comprising six mRNAs (MAGE A3, CLDN6, KK-LC-1, PRAME, MAGE A4, MAGE C1), each encoding a tumor-associated antigen (TAA) frequently expressed in NSCLC. Here, we present preliminary results from pts with advanced unresectable or metastatic NSCLC (ECOG 0-1) receiving BNT116 + docetaxel (DTX). Methods: LuCa-MERIT-1 (NCT: 05142189, EudraCT: 2021-004739-94) is a first-in-human, open label, Phase I trial to determine safety (dose limiting toxicities [DLTs]; treatment-emergent adverse events [TEAEs]) and clinical activity (RECIST v1.1) of BNT116 alone or in combinations. The cohort reported here will inform the dose of BNT116 in combination with DTX. Pts must have progressed on PD-1/PD-L1 inhibitor and a platinum-based chemotherapy. Biomarker analysis includes e.g., immunogenicity (ELISpot, n=3), cytokines (MSD, n=20), ctDNA (Avenio ctDNA Surveillance, n=~20), and PD-L1 (IHC, n=20). Results: As of 01 DEC 2023, 20 pts (median age 66 years) have received BNT116 in addition to DTX at 75 mg/m2 Q3W. The combination demonstrated a manageable safety profile. All pts experienced at least one TEAE. TEAEs ≥Grade 3/4, (incidence rate ≥10%) include neutropenia (n=10 [50%]), pneumonia (n=3 [15%]), hypertension (n=3 [15%]), lymphocyte count decreased, diarrhea, and fatigue (each n=2 [10%]). Serious TEAEs were observed in ten pts (50%), of which three were considered as related to BNT116 (Grade 3 cytokine release syndrome, Grade 3 bronchospasm, and Grade 3 pyrexia) and three were considered as related to DTX (Grade 3 diarrhea, Grade 3 rash, and Grade 4 febrile neutropenia). No DLTs within the dose confirmation period or deaths under treatment were observed. Seven of 20 pts (35%) had a partial response, 10 of 20 pts (50%) had stable disease. The objective response rate was 35% (95% CI: 15.4-59.2) and the disease control rate was 85% (95% CI: 62.1-96.8). Robust antigen-specific T-cell responses and cytokine induction were observed even with the addition of DTX and the use of prophylactic dexamethasone on Day 2 of each cycle. Conclusions: BNT116 + DTX shows encouraging antitumor activity, consistent induction of immune responses, a manageable safety profile, and no signs of additive toxicity. Updated safety and clinical activity data will be presented along with additional biomarker data. (Funded by BioNTech) Citation Format: Bala Başak Öven, David Vicente Baz, Jürgen Wolf, Ozturk Ates, Erdem Göker, Patrick Brück, Michael Wenger, Neru Munshi, Iryna Tsyhankova, Iryna Tsyhankova, Malgorzata Kaczorowska, Thomas Schell, Janet L. Markman, Huyuan Yang, Özlem Türeci, Uğur Şahin, Patrick Forde, Akin Atmaca. Preliminary results from LuCa-MERIT-1, a first-in-human Phase I trial evaluating the fixed antigen mRNA vaccine BNT116 + docetaxel in patients with advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT051.

Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cord compression, or hypercalcemia. Bone-modifying agents (BMAs), such as denosumab and zoledronic acid, are crucial in reducing the frequency and severity of SREs. The inhibition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has emerged as the standard treatment for hormone receptor-positive metastatic breast cancer, demonstrating significant improvements in survival outcomes. This study aims to compare the effectiveness of denosumab and zoledronic acid in preventing SRE in patients receiving CDK4/6 inhibitors with endocrine therapy. Materials and Methods: This retrospective study included 328 patients diagnosed with bone metastatic breast cancer receiving first-line CDK4/6 inhibitor therapy (palbociclib or ribociclib). Patients were assigned to receive either subcutaneous denosumab or intravenous zoledronic acid every 4 weeks. Time to the first skeletal-related event post bone-modifying agent initiation, SRE incidence, and the safety data were evaluated. The data were analyzed using independent samples t-tests, chi-square tests, and Kaplan–Meier methods for time-to-event data. Results: In the denosumab group, the median time to the first skeletal-related event was significantly longer than in the zoledronic acid group (44.55 months and 29.16 months, respectively). Denosumab treatment was associated with a statistically significant reduction in the risk of developing the first SRE after bone-modifying agent initiation compared to zoledronic acid (HR: 0.56, p = 0.001). Additionally, ECOG PS and the number of metastatic bone sites were identified as independent prognostic factors for time to the first SRE. The safety profile was consistent with previous studies reported in the literature. Conclusions: Our study demonstrated that when used with CDK4/6 inhibitors, denosumab is associated with a delay in SREs and a lower SRE incidence than zoledronic acid in patients with bone metastases. These findings support the efficacy of denosumab in preventing SREs and suggest that CDK4/6 inhibitors may have distinct effects on the bone microenvironment, particularly when combined with denosumab.

Background/Objectives: Dose reductions in CDK4/6 inhibitors, such as ribociclib and palbociclib, are often necessary due to treatment-related toxicities in patients with advanced breast cancer. This study aims to evaluate the impact of the timing of dose reductions on progression-free survival (PFS) and overall survival (OS) in a real-world cohort. Methods: This single-center, retrospective study included patients treated with ribociclib or palbociclib between 2019 and 2023 at a cancer center in Turkey. Dose reductions due to drug-related toxicities were recorded, and survival outcomes were analyzed. Patients were categorized based on the timing of dose reductions: within the first 3 months (early) and after 3 months (late). Results: Among 392 patients (mean age 57.13 years), 16.8% had dose reductions within 3 months, 21.7% had late dose reductions, and 61.5% had no dose reductions. The mPFS was 14.26 months for early dose reductions, 33.12 months for late dose reductions, and 20.6 months for no dose reductions (p < 0.001). The mOS was 37.12 months for early dose reductions, not reached for late dose reductions, and 57.76 months for no dose reductions (p < 0.001). Hematological toxicity, primarily neutropenia, was the most common cause of dose reductions. The ECOG performance status, line of therapy, and CDK4/6 inhibitor type were also significant predictors of PFS and OS. Conclusions: Early dose reductions in CDK4/6 inhibitors negatively affect PFS and OS, highlighting the importance of maintaining treatment intensity in the first 3 months. However, late dose reductions do not negatively affect progression-free survival (PFS) or overall survival (OS), with late dose reductions associated with better outcomes. Prospective studies in larger patient populations will further clarify our knowledge on this subject.

Objective To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy. Methods A retrospective analysis was conducted on 654 patients with stage IB3–IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival. Results The median cumulative cisplatin dose was 210 mg (range 40–320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1–150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin <10 g/dL before chemoradiotherapy as poor prognostic factors for both progression free survival and overall survival in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose 200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.