Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication.

BACKGROUND: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. PATIENTS AND METHODS: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. RESULTS: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). CONCLUSIONS: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Evolution of quality of life in patients with breast cancer during the first year of follow-up in Morocco.

BACKGROUND: Quality of life has an important place in the future of patients with breast cancer. The objective of this study is to assess the evolution of the patient's quality of life with breast cancer in Morocco after a year of follow-up. METHODS: This study involved the patients with breast cancer with all types of treatment as determined by their physicians. Patient's quality of life was assessed with the Moroccan Arabic version of QLQ- EORTC QLQ C30 and EORTC-BR23 questionnaires. Data were analyzed using SPSS Version 20 software. RESULTS: Regarding EOTRC questionnaires QLQ C-30, there was a significant improvement in global health status and all scales of the functional dimension except the social functional where there was a trend towards improvement and the financial impact of the disease where the situation has deteriorated. Quality of life was improved for most symptom-sized scales dimension of EORTC QLQ- C30 with the exception of diarrhea where it was observed degradation. Most of the EORTC QLQ-scales BR23 questionnaires showed a favorable trend in the quality of life except those of sexual functioning, sexual enjoyment, hair loss and the side effects of systemic therapy. CONCLUSION: The quality of life of the patient is significantly improved after 1 year of follow up. Quality of life instruments can be useful in the early identification of patients whose score low on functional scales and symptoms.

[Targeted therapy in thyroid cancer: Towards a treatment card]. / Les thérapies ciblées dans le cancer de la thyroïde: vers un traitement personnalisé?

Thyroid cancer is an uncommon cancer. Molecular biology plays a vital role in its development. Chemotherapy showed unsatisfactory results in advanced stages where surgery and iodine therapy are not appropriate. These last ten years have been marked by a major advance in understanding the molecular features of this cancer and therapeutic correlations, moreover, clinical trials have focused on the treatment of this disease on metastatic stages and led to a significant therapeutic panel targeting angiogenesis, mutations frequently found in cervical cancer: RET, BRAF, RAS... these are the motesanib, axitinib, sunitinib, pazopanib, vandetanib, cabozotinib and sorafenib. The last three molecules have already the autorisation of FDA and EMA. In this review, we will put the item on oncogenetic characteristics of thyroid carcinoma as well as new targeted therapies in patients refractory to conventional treatment.

Prognostic impact of the combination of erythropoiesis-stimulating agents to cancer treatment: literature review.

Cancer patients commonly develop anaemia. Erythropoiesis-stimulating agents (ESAs) are frequently used in cancer treatment. Numerous controlled studies indicate that ESAs can raise haemoglobin levels, reduce transfusion requirements and improve quality of life in anaemic cancer patients receiving chemotherapy. They were previously used to enhance response to radiation therapy, via increasing tumour cell oxygenation. Since the 2002 guideline, there has been increasing attention to the safety of ESA treatment in patients with cancer. Two placebo-controlled phase III randomised clinical trials published in 2003 showed evidence of harmful effects of ESAs on survival and/or tumour outcomes. Subsequently, recent trials and several large meta-analyses have confirmed negative impact on survival and/or disease progression. To comprehensively examine whether ESA use affects safety outcomes in cancer patients in different settings (chemotherapy, radiotherapy and targeted therapies), we conducted a literature review of all clinical trials, small and large meta-analyses from 1990 to 2012.

[Dietary risk factors of undifferenced nasopharyngeal carcinoma : a case-control study]. / Les facteurs de risque alimentaires du carcinome indifférencié du nasopharynx : Une étude cas témoin.

BACKGROUND: The incidence of nasopharyngeal carcinoma (NPC) is relatively high in Maghreb countries. This cancer is a model of multifactorial oncogenesis, but the role of food as risk factor in ethiopathogenesis of this tumor is not negligible. AIM: To identify the association between risk of NPC and some dietary factors in Morocco. METHODS: It is a case-control study including all new cases of NPC in our department between December 2009 and May 2010. Frequency consummation of foods was compared between cases and controls matched for age, sex and socio economic level. A high frequency consummation of a food was defined as consumption once or more by a week. Some traditional foods in Moroccan cooking like Harissa (hot red pepper), Qadid (mutton dried and salted), Khlii (dried meat, salted, spiced cooked and preserved in a mixture of oil and rendered beef fat) and Smen (rancid butter) were analyzed in this study. A conditional logistic regression was used to identify the association between dietary factors and the risk of NPC. RESULTS: Cases were more likely to have high frequency consumption of Harissa, Smen and Black Pepper, and less frequency consumption of fruts and vegetables. There was significant association between the risk of NPC and the frequency consumption of Qadid, khlii and cooking with olive oil. CONCLUSIONS: Some of these risk factors (Harissa, Black pepper) were found in 3 North Africain studies. This study indicates the involvement of dietary factors, and thus the lifestyle in the development of NPC and the need of biochemical analysis of food specimens to search for the carcinogenic agents.

Neoadjuvant endocrine therapy with or without palbociclib in low-risk patients: a phase III randomized double-blind SAFIA trial.

BACKGROUND: The most prevalent subtype of breast cancer (BC) is luminal hormonal-positive breast cancer. The neoadjuvant chemotherapy regimens have side effects, emphasizing the need to identify new startegies. OBJECTIVE: Analyze the complete pathologic response (pCR) rate and overall response in a low-risk hormone-positive subset of patients receiving neoadjuvant hormone treatment (NAHT) with or without Palbociclib (a CDK4/CDK6 inhibitor) to boost NAHT effectiveness. MATERIALS AND METHODS: Based on the upfront 21-gene Oncotype DX or low-risk Breast Recurrence Score assay (RS™), the SAFIA trial is designed as a prospective multicenter international, double-blind neoadjuvant phase-III trial that selects operable with luminal BC patients that are HER2-negative for the induction hormonal therapy with Fulvestrant 500 mg ± Goserelin (F/G) followed by randomization of responding patients to palbociclib versus placebo. The pCR rate served as the study's main outcome, while the secondary endpoint was a clinical benefit. RESULTS: Of the 354 patients enrolled, 253 initially responded and were randomized to either F/G fulvestrant with palbociclib or placebo. Two hundred twenty-nine were eligible for the evaluation of the pathologic response. No statistically significant changes were observed in the pCR rates for the patients treated with the F/G therapy with placebo or palbociclib (7% versus 2%, respectively) per the Chevallier classification (Class1 + Class2) (p = 0.1464) and 3% versus 10% assessed per Sataloff Classification (TA, NA/NB) (p = 0.3108). Palbociclib did not increase the rate of complete pathological response. CONCLUSION: Neoadjuvant hormonal therapy is feasible in a selected population with a low RS score of < 31 CLINICAL TRIAL: NCT03447132.

[Targeted therapies in digestive oncology]. / Les thérapies ciblées dans la cancérologie digestive.

Targeted therapies have an increasing importance in digestive oncology. These new treatments have been authorized in colon cancer, gastric cancer, pancreatic cancer, endocrine cancer and gastrointestinal stromal tumors. The oncologist should develop high abilities to use these therapies especially concerning the indications, response's biomarkers, toxicities and evaluation methods.

[Protein tyrosine kinase inhibitors in cancer therapy]. / Bilan des inhibiteurs de protéine tyrosine kinase dans le traitement des cancers.

The tyrosine kinase inhibitors (TKI) are small molecules of low molecular weight that inhibit tyrosine kinases, enzymes responsible for the activation of signal transduction cascades. Currently, a number of TKI received approval in various cancers, while others are in clinical development process: TKI are specifically clinically active when they target a tyrosine kinase (TK) with constitutional activity subsequent to a mutation, being then a master-gene driving transformation and tumour progression. Already, this drug-family provides a major therapeutic weapon against cancer.

Aggressive ovarian psammocarcinoma: a case report.

Serous psammocarcinoma is a rare form of ovarian carcinoma characterized by massive psammoma body formation. We report a new case of aggressive ovarian psammocarcinoma with omental and peritoneal implants.

[The role of chemotherapy in the management of bladder cancer]. / Rôle de la chimiothérapie dans la prise en charge du cancer de la vessie.

Bladder cancer represents for man the second genitourinary cancer after prostate cancer. Urothelial carcinoma is the most predominant histological type. In up to 70% of the cases, the diagnosis of bladder cancer is performed at early stages (Ta-T1). In this situation, the treatment of the disease is the transurethral resection with or without intravesical treatment (BCG, Amiticyne). In advanced disease, treatment is essentially palliative with chemotherapy based on cisplatin type MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) or gemcitabine-cisplatin. In invasive stages (T2-T3-T4), the radical cystoprostatectomy combined with urinary diversion for man, and the pelvectomy for woman are the gold standard. However, over 50% of these patients experienced metastatic recurrence during their evolution, which prompted investigators last 10 years to assess the value of néoadjuvant chemotherapy in their management. Indeed, neoadjuvant chemotherapy is now recognized as a standard by numerous American and European institutions. However, adjuvant chemotherapy remains controversial even for patients with lymph node involvement. The purpose of this literature review is to highlight the role of chemotherapy in the management of urothelial carcinoma of bladder with locally advanced and metastatic disease. The role of targeted therapies alone, in combination with chemotherapy, and in maintenance, is being evaluated.

Transitional cell carcinoma of the ovary: a rare case and review of literature.

INTRODUCTION: Transitional cell carcinoma (TCC) of the ovary is a rare, recently recognized, subtype of ovarian surface epithelial cancer. CASE PRESENTATION: A 69-year-old postmenopausal woman presented with a 2-year history of progressive enlargement of an abdominal mass. Abdominal computed tomography showed a pelvic mass. CA-125 was normal. A staging operation with total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy and pelvic lymph node dissection was performed. After surgery, the pathologic report of the right ovarian tumour was TCC, grade 3, stage IC. The patient underwent 3 cycles of chemotherapy: carboplatin and paclitaxel. She is regularly followed up and has been disease free for 10 months CONCLUSION: Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian cancer. Surgical resection is the primary therapeutic approach, and patient outcomes after chemotherapy are better than for other types of ovarian cancers.

[Primary adenoid cystic carcinoma in breast]. / Carcinome adénoïde kystique primitif du sein.

Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm. We report two observations occurring in female patients, 54 and 65 years old, who consulted for a mastodynia. Clinical examination showed limited painful breast nodules. On ultrasound and mammography they are well-limited bulky mass without microcalcifications. Diagnosis was based on final histopathological exam completed by immunohistochemistry or after slides review. The two patients were treated by mammectomy plus adjuvant radiotherapy and remain alive in remission with a follow-up of 29 and 36 months.

[Phyllodes tumors of the breast: analysis of 53 patients]. / Tumeurs phyllodes du sein à propos de 53 cas.

PURPOSE: Phyllode tumors of the breast are fibroepithelial tumors similar to fibroadenomas but with a predominant conjunctive tissue component. These are composed of a connective tissue stroma and epithelial elements. They are rare with an incidence of 0.3-0.9% of all breast neoplasms. The present study demonstrates the recent experiences in diagnosis, therapeutical management and clinical follow-up of this disease. PATIENTS AND METHODS: This is a retrospective study of the experience of the Institut National d'Oncologie (INO, Rabat) from 1998 to 2006. RESULTS: We included 53 patients. Median age was 37.2 years (15-67), tumor size was 1-30cm (median 10.25cm). The histological diagnosis was based on the biopsy in (7.8%) cases and extemporany in 22% cases, distant metastasis occurred in two patients; the treatment consisted of a surgery. The median follow-up was three years. Local recurrence occurred in ten patients. Distant metastasis occurred in two patients and five patients have died. CONCLUSION: The confrontation of our results to the data of the international literature shows that the diagnosis of the phyllodes tumours is histological. The basis of the treatment is surgery. The adjuvant radiotherapy is very important in patients at high risk for local recurrence; chemotherapy has a badly defined place. The prognostic is based on the histological characters of the tissue conjunctive component of these tumours.

[Meningeal carcinomatosis in breast cancer: from diagnosis to treatment]. / Carcinomatosis meningea en el cancer de mama: del diagnostico al tratamiento.

The appearance of meningeal carcinomatosis in breast cancer is an event that is being reported increasingly more frequently in the literature. It seems to be related with the lengthening of the patients' lives, improved sensitivity to diagnostic imaging and impermeability of the blood-brain barrier to the chemotherapeutic agents. It is an evolutionary form that affirms the metastatic invasion of the subarachnoidal space and is correlated with limited survival. Its diagnosis is difficult, due to the lack of specificity of the clinical signs dominated by headaches, cognitive disorders and possible signs and symptoms of progressive focal lesions. Magnetic resonance imaging of the brain and the spinal cord interpreted by a specialist in neuro-oncology is the preferred examination in this indication, in the search for an increase in meningeal enhancement. Biological analysis of the cerebrospinal fluid is an essential element in the diagnosis. In addition to the biochemical study, the presence of neoplastic cells is in itself enough to confirm the diagnosis. False negatives are very common and represent an important diagnostic problem that entails the need to repeat the lumbar punctures. The therapeutic methods are standard, often invasive, dominated by intrathecal chemotherapy and are based on low-level scientific evidence. This study analyses the epidemiology, the prognostic factors, the diagnostic tools, currently available treatments and the possible future therapies of meningeal carcinomatosis in breast cancer.

TITLE: Carcinomatosis meningea en el cancer de mama: del diagnostico al tratamiento.La aparicion de carcinomatosis meningea en el cancer de mama es un suceso cada vez mas comunicado en la bibliografia. Parece relacionarse con el alargamiento de la vida de las pacientes, la mejor sensibilidad al diagnostico por imagen y la impermeabilidad de la barrera hematoencefalica a los agentes quimioterapicos. Es una forma evolutiva que afirma la invasion metastasica del espacio subaracnoideo y se correlaciona con una supervivencia limitada. El diagnostico es dificil, debido a la inespecificidad de los signos clinicos dominados por cefaleas, trastornos cognitivos, y posibles sintomas y signos de lesiones focales progresivas. La resonancia magnetica del cerebro y de la medula espinal interpretada por un especialista en neurooncologia es el examen de eleccion en esta indicacion, en busqueda de un incremento en la captacion meningea. El analisis biologico del liquido cefalorraquideo es un elemento esencial en el diagnostico. Ademas del estudio bioquimico, la presencia de celulas neoplasicas es por si sola suficiente para confirmar el diagnostico. El numero de falsos negativos es muy comun y representa un gran problema diagnostico que requiere una repeticion de las punciones lumbares. Los metodos terapeuticos son estandares, a menudo invasivos, dominados por la quimioterapia intratecal y se basan sobre una evidencia cientifica de bajo nivel. Se analiza la epidemiologia, los factores pronosticos, las herramientas diagnosticas, los tratamientos disponibles en la actualidad y las posibles terapias futuras de la carcinomatosis meningea en el cancer de mama.

[Chemotherapy in nasopharyngeal carcinoma]. / La chimiothérapie dans les cancers du cavum.

UNLABELLED: Nasopharyngeal carcinoma (NC), especially the undifferenciated type, is a rare malignant disease. Prevalence is high in Southeast Asia and North Africa. OBJECTIVES: To determine the role of chemotherapy in the treatment of cancers of the nasopharynx. MATERIAL AND METHODS: [corrected] A search of the MEDLINE databases from 1970 to 2005, for articles testing chemotherapy in nasopharyngeal carcinoma. The key words: Nasopharyngeal carcinoma, chemotherapy, concurrent chemo-radiation, were used to access to principal trials. RESULTS: Nine phase III randomised trials, testing the combination of chemotherapy and radiotherapy in nasopharyngeal carcinoma were found. There us increasing evidence attesting to the beneficial effect of adding of chemotherapy to radiotherapy in the treatment of locally advanced disease (stage III and IV), especially concurrent chemo-radiation, considering the benefit in terms of overall survival. Associations containing cisplatin proved to be most effective. New molecules (capecitabine, taxanes, gemcitabine...) are currently in the course of testing, in phase II studies, for recurrent and metastatic NC, for which there is not still standard treatment. CONCLUSION: Medline review reveals that concurrent chemo-radiation, containing cisplatin, is standard treatment for locally advanced nasopharyngeal carcinoma. Metastatic disease is treated by palliative chemotherapy.

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature]. / Carcinome adénoïde kystique du nasopharynx, une entité clinique rare en quête d'innovations thérapeutiques : cas clinique et revue de la littérature.

Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences.

Novel agents in second-line therapy for EGFR wild-type Advanced Non-Small-Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide owing to its advanced-stage at the time of diagnosis. The majority of patients will require a second-line therapy after progression during first-line treatment. While treatment for NSCLC with EGFR mutation or EML4/ALK fusion, target therapy is the favored second-line therapy if not already used in first-line therapy, NSCLC with EGFR wild-type remains an unmet need and many oncologists favor cytotoxic therapy. Recently, a better understanding of lung cancer biology, with a better selection of patients based on histology, molecular biology and the identification of potential target antigens in the immune system have significantly improved patient outcome. This article will provide an update on different treatment options available for patients with EGFR wild-type advanced NSCLC who relapse after first-line therapy, which includes essentially ramucirumab, vandetanib, nivolumab, and pembrolizumab and considerations that may allow clinicians to a better choice of agent for second-line therapy.

[Male breast cancer in Morocco: Epidemiology and prognostic factors. A report of 140 cases]. / Cancer du sein chez l'homme au Maroc : épidémiologie et facteurs pronostiques. À propos de 140 cas.

OBJECTIVES: Male breast cancer is rare; it constitutes 0.2-1.5 % of all malignant tumors in men and 1 % of all breast cancers. METHODS: The goal of this retrospective study is to analyze the epidemiologic, clinic, therapeutic and evolutive profiles of this disease in 140 cases collected at the National Institute of Oncology and military hospital in Rabat, Morocco, between the years 1998 and 2007. RESULTS: The mean age was 61 years. A high incidence of overweight was found. The most frequent clinical presentation was a firm subareolar lump in 83 % of cases. The most common pathological type was an infiltrating ductal carcinoma (93 %). Hormone receptors were positive in 86 % of cases. Eighty-five percent of patients underwent simple mastectomy and axillary dissection, 68 % chest wall irradiation after surgery, 54 % received chemotherapy and 82 % hormonal therapy. Median follow-up was 91.1 months. The estimated 5-year and 10-year overall survival was respectively 68 % and 74 %. CONCLUSION: The management of male and female breast carcinoma is the same, as well as their prognosis at equal stages. Future research for better understanding of this disease are needed to improve the management and prognosis of male patients.

FOLFOX as Perioperative Chemotherapy of localized Gastric Cancer: Efficacy and Tolerance.

BACKGROUND: Use of perioperative chemotherapy had significantly improved prognosis of localized gastric cancer. Two studies have validated this approach using cisplatin based chemotherapy despite important toxicities. We conducted this study with the aim to evaluate efficacy and toxicity of FOLFOX regimen in this setting. MATERIAL AND METHODS: This is a retrospective study including patients followed for gastric cancer in the Oncology Department of the military hospital Mohamed V in Rabat, Morocco over a period of 7 years from 2007 to 2013. Patients received 4 cycles of mFOLFOX as perioperative regimen. Assessment of tumor response after completion of preoperative chemotherapy was granted by comparative CT scan, tumor markers measurements and R0 surgery rate.Adverse events were graded according to classification of the National Cancer Institute Common Toxicity Criteria version 4.0. RESULTS: Thirty-one patients were included in this study. Use of preoperative chemotherapy showed partial response in fourteen patients (45.1%), stabilization in fifteen patients (48.4%). Tumor markers CEA and CA 19- 9 were significantly decreased. R0 resection rate was 83.87%. Only 2 (6.45%) cases of grade 3/4 hematologic toxicity were reported in our study. Achieving programmed postoperative chemotherapy was possible in 72.41% of patients. CONCLUSIONS: Our study is limited by the retrospective design and small sample size but FOLFOX chemotherapy seems effective and well tolerated in this setting and its place deserves to be studied in a larger study.