Trastuzumab-induced cardiotoxicity (TIC) can lead to early treatment discontinuation. The aim of this study was to evaluate: N-terminal brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), myoglobin, and selected biochemical and clinical factors as predictors of TIC. One hundred and thirty patients with HER2-positive BC receiving adjuvant trastuzumab therapy (TT) were enrolled. Measurement of cardiac markers and biochemical tests as well as echocardiography were performed prior to TT initiation and every three months thereafter. Cardiotoxicity leading to treatment interruption occurred in 24 patients (18.5%). While cardiotoxicity caused early treatment discontinuation in 14 patients (10.8%), the TIC resolved in 10 (7.7%) and TT was resumed. The most common complication was a decrease in left ventricular ejection fraction of more than 10% from baseline or below 50% (7.7%). In patients with TIC, there was no increase in the levels of NT-proBNP, myoglobin, and CK-MB. BMI, hypertension, ischemic heart disease, diabetes, age, cancer stage, type of surgery, use of radiotherapy, chemotherapy, and hormone therapy were shown to not have an effect on TIC occurrence. NT-proBNP, myoglobin, and CK-MB are not predictors of TIC. There is an ongoing need to identify biomarkers for TIC.

No abstract

Nivolumab and ipilimumab combination became the first-line standard in advanced melanoma. We assessed its efficacy in a real-life study in Poland. In a one-year follow-up, we evaluated the medical records of 50 melanoma patients treated with that modality in five oncology centers. We recorded therapy outcomes and adverse events (AEs) after 3 and 12 months of therapy. At the first checkpoint, the disease control rate (DCR) was recorded in 58% (n = 29) of patients, but the same number of patients (n = 29, 58%) stopped immunotherapy due to disease progression (PD, n = 14, 48.3%), toxicity (n = 11, 37.9%) or death (n = 4, 13.8%). Among patients with DCR after the induction phase, 8 (27.6%) terminated due to toxicity, and 21 (72.4%) continued. However, at the 12-month checkpoint, only 14 patients (27% of all) were still receiving immunotherapy. In 7 (33.3%) it was discontinued due to PD (n = 2), toxicity (n = 2, 28.6% each), or death (n = 3, 42.9%). AEs occurred in 66.7% (n = 34) of patients; severe (grade 3 or 4) in half of them. Interestingly, those with AEs had an 80% lower risk of death (hazard ratio [HR] 0.2, 95% confidence interval [CI] 0.07–0.57, p = 0.001) and PD (HR 0.2, 95%CI 0.09–0.47, p < 0.0001). In the entire group of patients, after a 12-month follow-up, the median overall survival was not reached (NR, range: 6.8 months-NR) and progression-free survival was 6.3 (range: 3-NR) months. Our results demonstrate that combined immunotherapy is less effective in real-life than in pivotal trials. However, early responders will likely continue the therapy after a one-year follow-up. AEs occurrence might be a predictor of clinical effectiveness.

Immune checkpoint inhibitors have significantly improved the prognosis of melanoma patients. However, these therapies may trigger unexpected immune-related adverse events (irAEs), which are challenging in making the proper diagnosis and providing treatment. Hematological toxicities are possible irAEs, but were poorly evaluated in clinical trials and treatment recommendations of this specific complications are limited. We present a stage IV melanoma patient who developed an extremely rare toxicity – hemophagocytic lymphohistiocytosis (HLH) after the 4th course of combined immunotherapy with nivolumab and ipilimumab. The patient was steroid resistant and only the treatment with various immunosuppressive agents provided control of the disease and finally melanoma regression. In this report, we evaluated the methods of HLH treatment and described our modification of available protocols. Immediate immunosuppression can be life-saving and due to rarity of this condition as well as lack of specific recommendations, every report is valuable for clinicians, especially when treatment was effective.

No abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the main cause of cancer-related death worldwide. The available treatment options for HCC include liver transplant, locoregional therapy (such as ablation, embolization, and radiotherapy), and systemic treatment. The latter encompasses targeted therapy, immunotherapy, and angiogenesis inhibitors, alone or in combination. The introduction of immune checkpoint inhibitors and targeted drug therapy has been one of the most significant advances in HCC treatment. These therapies were shown to prolong overall survival and progression-free survival in clinical trials including patients with advanced HCC. In recent years, the systemic treatment of advanced HCC has vastly improved, with a median survival of 19.2 months in the IMbrave150 trial. However, further research is needed to determine the optimal sequence of treatment.

e21511 Background: The combination of nivolumab and ipilimumab has become the standard of care for the first-line treatment of advanced melanoma. In this study, our objective was to evaluate the frequency of immune-related adverse events (irAEs) and to establish their relationship with treatment outcomes. Methods: We evaluated the medical records of 99 patients with advanced melanoma treated with combined immunotherapy in 7 oncology units in Poland in the period between October 2020 (the beginning of the reimbursement policy) and October 2022. We recorded therapy efficacy and irAEs at a follow-up period of 3, 12 and 18 months. Responders were defined as the patients with at least stable disease in a first follow-up, and non-responders as those with progressive disease (PD). The associations between the occurrence of irAEs and the treatment results (overall survival [OS] and progression-free survival [PFS]) were calculated using the Cox proportional hazards model. The log-rank test was applied to compare the survival distribution between the chosen factors. Results: The median duration of treatment was 2 months (interquartile ranges [IQR]: 2-6) and during the analysis, the patients were observed for a median follow-up of 6 months (IQR:3-13). After 3 months, the respondents constituted 54.5% (n = 54). At the last follow-up, 33.3% (n = 33) of the patients continued treatment and immunotherapy was stopped in the remaining patients due to PD (n = 33, 33.3%), toxicity (n = 24, 24.2%) or death (n = 8, 8.1%). In the entire group, the median OS was not reached (NR), (IQR: 8.7 months -NR) whereas PFS was 7 months (IQR:2-NR). Any grade (G) of irAEs was reported in 65 individuals (65.7%) with G3/G4 in 28 of them (43%). Thirty-one patients developed more than one episode of irAEs (2 episodes in 17.2%, n = 17; 3 episodes in 10.1%, n = 10; 4 episodes in 4%, n = 4; p = 0.006). The frequency of irAEs was 83.3% (n = 45) and 44.7% (n = 17) in responders and non-responders respectively, p = 0.0001. The OS and PFS values for patients who experienced irAEs did not reach medians and upper quartiles, but those without any irAEs had significantly worst outcome (10.5 months [IQR: 3-NR] for OS, p = 0.002; 2 months [IQR: 2-5.2] for PFS, p = 0.01). The patients with irAEs had a 30% lower risk of death (hazard ratio [HR] 0.7, 95% confidence interval [CI 0.56-0.86]) and a 40% lower risk of PD (HR 0.6, 95%CI [0.48- 0.74]). The most common irAEs were endocrine (n = 25), hepatic (n = 22) and cutaneous (n = 17). In a pairwise comparison the patients with endocrine irAEs (p = 0.01), receiving immunosuppressants for irAEs treatment (p = 0.01), and without brain metastases (p = 0.02) had a better survival rate. Conclusions: Patients with advanced melanoma treated with combined immunotherapy who experienced irAEs have a more favorable outcome, which is even better in those with more episodes of toxicity. The type of irAEs may also have predictive value.