Real world evidence of adjuvant trastuzumab in HER2 positive early breast cancer.

Adjuvant trastuzumab in HER2+ breast cancer reduces recurrence and mortality, and has been the standard treatment since 2006. The objective was to analyze health outcomes in the real world. Observational, retrospective study of patients with HER2+ breast cancer, stages I-III, treated with adjuvant trastuzumab in the past 15 years in only one center and for the first time in Spain. Survival was analyzed according to the number of cycles and cardiotoxicity. Two hundred and seventy-five HER2positive patients (18.60%) out of 1479 received adjuvant (73%) or neoadjuvant/adjuvant (26%) trastuzumab, concomitantly (90%) or sequentially (10%) with chemotherapy. The probability of overall and disease-free survival (OS and DFS) at 5 years was 0.93 (95% CI 0.89-0.96), and 0.88 (95% CI 0.83-0.92). The number of cases with a significant and asymptomatic decrease in ventricular ejection fraction and heart failure were 54 (19.64%) and 12 (4.36%), respectively. Sixty-eight patients (24.70%) received 16 or fewer cycles, especially those older than 65 (OR 0.371, 95% CI 0.152-0.903; p = 0.029) and with cardiotoxicity (OR 15.02, 95% CI 7.437-30.335; p < 0.001). The risk of cardiotoxicity was associated with having received radiotherapy (OR 0.0362, 95% CI 0.139-0.938; p = 0.037). Arterial hypertension (HR 0.361, 95% CI 0.151-0.863, p = 0.022), neoadjuvant treatment (HR 0.314, 95% CI 0.132-0.750, p = 0.009) and cardiotoxicity (HR 2.755, 95% CI 1.235-6.143, p = 0.013) maintained significant association with OS. Only neoadjuvant treatment maintained a significant association with DFS (HR 0.437, 95% CI 0.213-0.899, p = 0.024). The effectiveness of neoadjuvant and adjuvant trastuzumab can be considered comparable to those of clinical trials. In the real world, factors such as age, hypertension, radiotherapy, neoadjuvant treatment, and cardiotoxicity should be taken into consideration to optimize outcomes.

Impact of intestinal dysbiosis-related drugs on the efficacy of immune checkpoint inhibitors in clinical practice.

PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.

[Analysis of the effectiveness of an antiemetic protocol used in an oncology division]. / Análisis de la efectividad de un protocolo de antiemesis implantado en la Unidad de Oncología.

OBJECTIVE: To analyse the effectiveness of an antiemetic protocol in patients receiving chemotherapy treatment. METHOD: Prospective study in patients with solid tumours receiving chemotherapy in an oncology day hospital between January 2006 and 2007. We conducted a literature review and an evaluation of the recommendations of different clinical practice guidelines. The emetogenic potential was calculated according to the Hesketh level (HL), and the antiemetic premedication was determined for each regimen. We evaluated the effectiveness of an antiemetic protocol by using a survey as a method for measuring emetic episodes and nausea in the acute and delayed phases. RESULTS: 172 patients completed the survey. 13.4% vomited in the acute phase and 16.9% in the delayed phase; the median number of times was 2 (1-8) and 1 (1-5) for each respective phase. With treatment regimens classed as HL 4-5, 18.5% experienced vomiting in the acute phase and 20.2% in the delayed phase, with 46% experiencing nausea in the acute phase and 38.4% in the delayed phase. Control of vomiting in patients with treatment regimens classed as HL 1-3 was 100% in acute phase and 91.7% in the delayed phase; nausea was reported by 27% in the acute phase and 31% in the delayed phase. The factors that contributed the most to the presence of vomiting and nausea were the emetogenic potential of the treatment regimen (p<0.05), vomiting in the previous cycle (p<0.05) and age younger than 50 years (p<0.002). DISCUSSION: The proposed antiemetic protocol is effective for controlling vomiting in chemotherapy regimens with an HL of 1-3. For highly emetogenic regimens, the antiemetic protocol is also effective, but protection is not complete. This protocol seems less effective for controlling nausea, although this is a subjective symptom which is difficult to assess and not routinely measured in clinical trials.

[Treatment with cetuximab in metastatic colorectal cancer patients who do not express the epidermal growth factor receptor]. / Tratamiento con cetuximab en pacientes con cáncer colorrectal metastásico que no expresan el receptor del factor de crecimiento epidérmico.

OBJECTIVE: To evaluate the response to cetuximab, in terms of time passed until disease progression and overall survival, in patients with colorectal cancer (CRC) in which the epidermal growth factor receptor (EGFR) is undetectable. METHOD: Nine EGFR-negative patients (confirmed by an immunohistochemistry study), who were being treated with cetuximab, were selected. Variables collected: demographic data, diagnosis, previous treatments, time since first metastasis to start of treatment with cetuximab, adverse events and tumour markers. The response was monitored using tumour markers and disease progression. Well-being was assessed using the Karnofsky performance status (KPS) or that of the Eastern Cooperative Oncology Group (ECOG). RESULTS: 22% men (2/9) with a median age of 48 (31-63). The median time from being diagnosed with the metastatic disease to the start of treatment with cetuximab was 19 months (12-48). All patients had failed an irinotecan-based regime, 77.77% (7/9) had also failed one which included oxaliplatin. The median number of cycles with cetuximab was 14 (6-32). The main adverse event was the appearance of an acneiform rash in 100% of the cases. The median time until disease progression was 7 months (3-16) and 10.2 months (4-24) for overall survival. The results for well-being showed a KPS of between 80-100% and an ECOG of < 2. The results obtained in the present study for overall survival and time until disease progression are higher than those in the pivotal study (10.2 compared to 8.6 months and 7 compared to 4.1 months respectively). CONCLUSIONS: According to the results obtained, the use of assessing the EGFR expression (by the immunohistochemistry technique at least), as a means of predicting response to treatment with cetuximab may be questioned. This suggests that selecting patients using the routine assessment of this receptor is inappropriate, since it excludes patients who may potentially benefit from the treatment. However, more clinical trials are required in this area in order to confirm these conclusions.