Real-world experience with pertuzumab and trastuzumab combined with chemotherapy in neoadjuvant treatment for patients with early-stage HER2-positive breast cancer: the NEOPERSUR study.

PURPOSE: HER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC. METHODS: A retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR). RESULTS: A total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3-7.7) and 7.3 (95% CI 7.1-7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3-4 anti-HER2 related toxicities were reported in six (1.9%) patients. CONCLUSION: Neoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.

Analysis of neutropenia as a predictive factor of the efficacy of trifluridine-tipiracil treatment.

OBJECTIVES: Trifluridine-tipiracil (TAS-102), an oral cytotoxic agent used in adult patients with refractory metastatic colorectal cancer (mCRC), has been associated with neutropenia (chemotherapy-induced neutropenia) (CIN)). MATERIALS AND METHODS: We evaluated the efficacy and safety of TAS-102 in a group of 45 mCRC patients (median age 66 years) in Huelva province, Spain, in a retrospective, multicenter observational study. RESULTS: We showed that the association between TAS-102 and CIN can be used as a predictor of efficacy. 20% (9/45) of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 had received at least one previous chemotherapy treatment. Overall, 75.5% (34/45) and 28.9% (13/45) had received anti-VEGF and anti-EGFR monoclonal antibodies, respectively. Additionally, 80% (36/45) of patients had received third-line treatment. The mean treatment period, duration of overall survival (OS), and duration of progression-free survival (PFS) were 3.4, 12, and 4 months, respectively. A partial response was seen in 2 patients (4.3%), and disease stabilization was observed in 10 patients (21.3%). Neutropenia was the most frequent grade 3 - 4 toxicity (46.7%; 21/45). Other findings were anemia (77.8%; 35/45), all grades of neutropenia (73.3%; 33/45), and gastrointestinal toxicity (53.3%; 24/45). The dose of TAS-102 needed to be reduced in 68.9% (31/45) of patients, whereas treatment needed to be interrupted in 80% (36/45) of patients. Grade 3 - 4 neutropenia was a positive prognostic factor for OS (p = 0.023). CONCLUSION: A retrospective evaluation shows that grade 3 - 4 neutropenia is an independent predictor of treatment response and survival in patients undergoing routine treatment for mCRC, but this finding needs confirmation in a prospective study.

Analysis of blood markers for early colorectal cancer diagnosis.

Background: Colorectal cancer (CRC) is a very common tumor worldwide. Its mortality can be limited by early diagnosis through screening programs. These programs are based on fecal occult blood testing and colonoscopy. Our objective was to find a model based on the determination of blood biomarkers that was efficacious enough to become part of the early diagnosis of CRC. Methods: In a total of 221 patients who underwent a colonoscopy, two types of markers were identified (I) classic: carcinoembryonic antigen (CEA), CA19.9, α-fetoprotein, CA125, CA72.4, and ferritin; and (II) experimental: neutrophil gelatinase-associated lipocalin (NGAL), estimated glomerular filtration rate (EGFR), 8-hydroxydeoxyguanosine (8OHdG), calprotectin, and cysteine-rich 61 (Cyr61). We divided the patients into four groups according to colonoscopy results: a control group (n=83) with normal colonoscopy, a polyp group (n=56), a CRC group (n=45), and an inflammatory disease group (n=37). We built an algorithm based on multivariate logistic regression analysis. Results: A total of 51.6% were males, and the median age was 63 years. We designed an algorithm based on the combination of several markers that discriminated CRC patients from the rest of the patients with a performance of 94%, a sensitivity of 95.6%, and a specificity of 80.6%. Discriminating by sex also resulted in two powerful algorithms, although it performed better in males (97% vs. 91%). Conclusions: Our study has devised a predictive model with high efficacy based on the determination of several biomarkers. We think that it could be incorporated into the set of methods used in CRC screening.

Author Correction: Validating a breast cancer score in Spanish women. The MCC-Spain study.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

[Physicians' awareness and assessment of shared decision making in oncology practice.] / onocimiento y evaluación de la toma de decisiones compartidas en la práctica oncológica desde el punto de vista médico.

OBJECTIVE: Implementation of Shared Decision Making (SDM) in oncology is limited. The objective of the study was to determine the extent of physicians' awareness of Shared Decision Making (SDM) in their treatment of cancer patients, the usefulness that they assign to SDM, the role they play, their assessment of SDM, and perceptions of the main barriers and facilitators to its use. METHODS: A questionnaire was completed by medical oncologists, radiation oncologists and general surgeons working in Andalusia (Spain). Sociodemographic, clinical-care and aspects of SDM variables were collected. SDM was evaluated using the SDM-Q-Doc questionnaire. Non-parametric contrasts were used to determine the possible differences between medical specialties. RESULTS: The questionnaire was sent to 351 physicians. The response rate was 37.04%, 63 women and 67 men, with an average age of 45.6 years and 18.04 years' experience. Of these, 33.08% were medical oncologists, 34.61% radiation oncologists and 29.23% general surgeons. A total of 82.3% stated they had received no training in SDM, whereas 33.8% said they knew a lot about SDM and applied it in practice; 80% considered it to be very useful. In addition, 60% of respondents said they were mainly the ones who made the decisions on treatment. An evaluation of SDM on the SDM-Q-Doc scale showed that all the specialities scored more than 80/100. The main barriers to applying SDM were the difficulty patients experienced in understanding what they needed to know, the lack of decision aids and time. CONCLUSIONS: Some 82% of physicians have no training in SDM and 66% don´t use it in practice, with decisions on treatment taken mainly by the physicians themselves. Strategies to increase training in SDM and to implement it into clinical practice are important.

OBJETIVO: La implementación de la Toma de Decisiones Compartidas (TDC) en oncología es escasa. El objetivo del estudio fue determinar el conocimiento de la TDC que tienen los médicos que tratan a pacientes con cáncer, la utilidad que le conceden, el rol que desempeñan, la evaluación que hacen, y las barreras y facilitadores que encuentran para su uso. METODOS: Se realizó una encuesta a oncólogos médicos, oncólogos radioterápicos y cirujanos generales que ejercían en Andalucía (España). Se recogieron variables sociodemográficas, clínico-asistenciales y de aspectos de la TDC. La TDC se evaluó mediante el cuestionario SDM-Q-Doc. Se emplearon contrastes no paramétricos para determinar las posibles diferencias entre especialidades médicas. RESULTADOS: El cuestionario se envió a 351 médicos y la tasa de respuesta fue del 37,04%. Respondieron 63 mujeres y 67 hombres, con un promedio de 45,6 años de edad y 18,04 años de experiencia. El 33,08% eran oncólogos médicos, el 34,61% oncólogos radioterápicos y el 29,23% cirujanos generales. El 82,3% no tenía formación en TDC y el 33,8% reconocía saber bastante y utilizarla en su práctica habitual. El 80% consideró que era muy útil. El 60% respondió que la decisión sobre el tratamiento la tomaban mayormente ellos. Al evaluar la TDC con la escala SDM-Q-Doc, todas las especialidades obtuvieron más de 80 puntos sobre 100. Las principales barreras para aplicar la TDC fueron la dificultad del paciente para entender lo que necesitaba saber, la falta de instrumentos de apoyo, así como la falta de tiempo. CONCLUSIONES: Un 82% de los médicos no tiene formación en TDC y un 66% no la utiliza en su práctica habitual, tomando la decisión sobre el tratamiento mayoritariamente ellos. Es importante adoptar estrategias para aumentar la formación en TDC e implementarla en la práctica clínica diaria.

[Analysis of non-scheduled consultations in patients with digestive neoplasms]. / Análisis de consultas no programadas en pacientes con cáncer digestivo.

OBJECTIVE: Non-scheduled consultation is very frequent among patients with cancer, creating alterations and delays in programmed visits. We describe the incidence of non-scheduled consultations in patients with digestive cancer in our hospital. METHODS: Descriptive, prospective, non-interventional study. In a six-month period (May-December 2017), non-scheduled visits were chronologically recorded in the medical oncology consultation of digestive tumours of Hospital Juan Ramón Jiménez de Huelva. We performed a descriptive analysis of the variables collected through the statistical program G-STAT v.2.0. RESULTS: Patients with colon or rectal cancer generated most consultations (68.63%). followed by pancreatic (9.15%) and gastric (5.23%). Most patients had metastatic or advanced stage cancer (59.87%) and were under palliative or symptomatic treatment (58.82%). The most frequent reason for consultation was clinical symptoms (47.05%). followed by information demand (18.30 %). CONCLUSIONS: Non-scheduled consultations in cancer patients are frequent; they cause interference in scheduled consultations and not always resolved satisfactorily. We propose several measures to reduce the number of non-scheduled consultation in oncology.

OBJETIVO: La demanda de asistencia no programada por parte de los pacientes oncológicos es muy frecuente (1,2) y conllevan alteraciones y retrasos en la actividad ya programada. Describimos la incidencia de consultas no programadas en pacientes con cáncer digestivo de nuestro centro. METODOS: Estudio descriptivo, prospectivo y sin intervención. Se recogieron cronológicamente en un periodo de 6 meses (15 de mayo al 14 de diciembre de 2017) y utilizando como fuente la historia clínica de los pacientes, las visitas no programadas atendidas en la consulta de oncología médica de tumores digestivos del Hospital Juan Ramón Jiménez de Huelva. Realizamos un análisis descriptivo de las variables recogidas mediante el programa estadístico G-STAT v.2.0. RESULTADOS: El mayor número de consultas fue realizado por pacientes con cáncer de colon o recto (68,63%), seguidas por los de páncreas (9,15%) y los gástricos (5,23%). La mayoría de los pacientes tenían un cáncer en situación metastásica o avanzada (59,87%) y estaban recibiendo tratamiento paliativo (58,82%) con quimioterapia o sintomático. El motivo de consulta más frecuente fueron los síntomas clínicos (47,05%), seguido por la demanda de información (18,30 %). CONCLUSIONES: Se constata una alta demanda de asistencia no programada por parte de los pacientes con cáncer digestivo, que interfiere con la asistencia programada y no siempre se resuelve satisfactoriamente. Se proponen varias medidas para reducir el número de estas consultas.

Validating a breast cancer score in Spanish women. The MCC-Spain study.

A breast-risk score, published in 2016, was developed in white-American women using 92 genetic variants (GRS92), modifiable and non-modifiable risk factors. With the aim of validating the score in the Spanish population, 1,732 breast cancer cases and 1,910 controls were studied. The GRS92, modifiable and non-modifiable risk factor scores were estimated via logistic regression. SNPs without available genotyping were simulated as in the aforementioned 2016 study. The full model score was obtained by combining GRS92, modifiable and non-modifiable risk factor scores. Score performances were tested via the area under the ROC curve (AUROC), net reclassification index (NRI) and integrated discrimination improvement (IDI). Compared with non-modifiable and modifiable factor scores, GRS92 had higher discrimination power (AUROC: 0.6195, 0.5885 and 0.5214, respectively). Adding the non-modifiable factor score to GRS92 improved patient classification by 23.6% (NRI = 0.236), while the modifiable factor score only improved it by 7.2%. The full model AUROC reached 0.6244. A simulation study showed the ability of the full model for identifying women at high risk for breast cancer. In conclusion, a model combining genetic and risk factors can be used for stratifying women by their breast cancer risk, which can be applied to individualizing genetic counseling and screening recommendations.

A rapid response to pembrolizumab in a patient with metastatic melanoma.

Prognosis for patients with metastatic melanoma stays poor. Recent advances in the field of immuno-oncology increased treatment options for these patients and gave chances for obtaining partial and even complete response, prolonging survival in a subset of patients. Here, we describe a case of a 55-year-old man with multiple melanoma metastases into lungs who showed an extraordinary response to pembrolizumab used as a first-line treatment. The therapy was well tolerated, with no adverse reactions reported.

A phase II study of weekly vinorelbine and trastuzumab in patients with HER2-positive metastatic breast cancer.

BACKGROUND: Trastuzumab combined with cytotoxic agents presents encouraging results in metastatic breast cancer (MBC), but cardiac toxicity limits some combinations. The synergism shown with trastuzumab and the favorable tolerability profile of vinorelbine provided the rationale for investigating this combination. PATIENTS AND METHODS: Patients with HER2-positive MBC who had received <2 lines of chemotherapy for metastatic disease were included. Vinorelbine (25 mg/m2 on day 2, then weekly on day 1) and trastuzumab (4 mg/kg on day 1, then 2 mg/kg weekly) were administered for a maximum of 6 cycles (1 cycle=3 weeks). RESULTS: A total of 52 patients were enrolled. The median age was 50 years (range, 26-79 years). Ninety percent of the patients had received adjuvant chemotherapy, 42% received a first line of chemotherapy for MBC, and 69% had disease at visceral sites. The overall response rate was 58% (95% CI, 43%-71%). The median time to progression and overall survival were 7 months (95% CI, 5-9 months) and 26 months (95% CI, 20-32 months), respectively. Grade 4 neutropenia was present in 3 courses; neutropenic fever was not reported. The main grade 3 nonhematologic toxicities were asthenia, neuropathy, diarrhea, alopecia, and nausea/vomiting. No patients experienced serious cardiac toxicity. CONCLUSION: These results confirm that weekly vinorelbine/trastuzumab is an active and safe regimen in patients with HER2-positive MBC with an unfavorable prognosis.