Panitumumab: the evidence for its use in the treatment of metastatic colorectal cancer

Panitumumab is the first fully human monoclonal antibody to Epidermal Growth Factor Receptor (EGFR) to enter clinical trials for the treatment of solid tumors. The anti-tumor activity of panitumumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in numerous cancer models, particularly lung, kidney and colorectal (CRC). Preclinical and clinical studies have established a role for panitumumab in metastatic colorectal cancer (mCRC) refractory to multiple chemotherapeutic regimens. Based on these encouraging findings, panitumumab was approved by the US Food and Drug Administration for the treatment of patients with epidermal growth factor receptor-expressing mCRC refractory to fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic regimens. The improvement in progression free survival (PFS) and response rate (RR) produced by panitumumab monotherapy was significantly greater in patients with non mutated (wild-type) K-RAS than in those with mutant K-RAS. Therefore implementing routine K-RAS screening and limiting the use of EGFR inhibitors to patients with wild-type K-RAS appears the better strategy for select only the patients who could benefit from the therapy with panitumumab and also may have the potential for cost savings. The purpose of this review was to evaluate the patient-related, disease-related and economic-related evidence for the use of panitumumab in the treatment of metastatic colorectal cancer in clinical practice

Eribulin in male patients with breast cancer: The first report of clinical outcomes

Background. Evidence on the management and treatment of male breast cancer is scant. We report the analysis of a multicenter Italian series of patients with male breast cancer treated with eribulin. To our knowledge, this is the first report on the use or eribulin in this setting. Patients and Methods. Patients were retrospectively identified in 19 reference centers. All patients received eribulin treatment, according to the standard practice of each center. Data on the identified patients were collected using a standardized form and were then centrally reviewed by two experienced oncologists. Results. A total of 23 patients (median age, 64 yearsrange, 42–80) were considered. The median age at the time of diagnosis of breast cancerwas 57 years (range, 42–74).HER2 status was negative in 14 patients (61%), and 2 patients (9%) had triple-negative disease. The most common metastatic sites were the lung (n 5 1461%) and bone (n 5 1356%). Eribulin was administered for a median of 6 cycles (range, 3–15). All patients reported at least stable diseasetwo complete responses (9%) were documented. Eribulin was well-tolerated, with only four patients (17%) reporting grade 3 adverse events and two (9%) with treatment interruptions because of toxicity. Eight subjects (35%) did not report any adverse event during treatment. For patients with a reported fatal event, the median overall survival from the diagnosis of metastatic disease was 65 months (range, 22–228). Conclusion. Although hampered by all the limitations of any retrospective case series, the results of the present study suggest, for the first time, the use of eribulin as therapy for male breast cancer

The Impact of Lifestyle Interventions in High-Risk Early Breast Cancer Patients: A Modeling Approach from a Single Institution Experience

none21noA healthy lifestyle plays a strategic role in the prevention of BC. The aim of our prospective study is to evaluate the effects of a lifestyle interventions program based on special exercise and nutrition education on weight, psycho-physical well-being, blood lipid and hormonal profile among BC patients who underwent primary surgery. From January 2014 to March 2017, a multidisciplinary group of oncologists, dieticians, physiatrists and an exercise specialist evaluated 98 adult BC female patients at baseline and at different time points. The patients had at least one of the following risk factors: BMI ≥ 25 Kg/m2, high testosterone levels, high serum insulin levels or diagnosis of MS. Statistically significant differences are shown in terms of BMI variation with the lifestyle interventions program, as well as in waist circumference and blood glucose, insulin and testosterone levels. Moreover, a statistically significant difference was reported in variations of total Hospital Anxiety and Depression Scale (HADS) score, in the anxiety HADS score and improvement in joint pain. Our results suggested that promoting a healthy lifestyle in clinical practice reduces risk factors involved in BC recurrence and ensures psycho-physical well-being.openMirco Pistelli, Valentina Natalucci, Laura Scortichini, Veronica Agostinelli, Edoardo Lenci, Sonia Crocetti, Filippo Merloni, Lucia Bastianelli, Marina Taus, Daniele Fumelli, Gloria Giulietti, Claudia Cola, Marianna Capecci, Roberta Serrani, Maria Gabriella Ceravolo, Maurizio Ricci, Albano Nicolai, Elena Barbieri, Giulia Nicolai, Zelmira Ballatore, Agnese Savini and Rossana BerardiPistelli, Mirco; Natalucci, Valentina; Scortichini, Laura; Agostinelli, Veronica; Lenci, Edoardo; Crocetti, Sonia; Merloni, Filippo; Bastianelli, Lucia; Taus, Marina; Fumelli, Daniele; Giulietti, Gloria; Cola, Claudia; Capecci, Marianna; Serrani, Roberta; Gabriella Ceravolo, Maria; Ricci, Maurizio; Nicolai, Albano; Barbieri, Elena; Nicolai, Giulia; Ballatore, Zelmira; Savini and Rossana Berardi, Agnes

Espressione di p-mTOR e del recettore degli androgeni nei tumori mammari triplo negativi: significato clinico e potenziali prospettive terapeutiche

Background: I carcinomi mammari triplo negativi (TNBC) presentano un comportamento clinico aggressivo dovuto anche alla mancanza di terapie target. La recente identificazione di un sottotipo molecolare correlato con l’attivazione del recettore degli androgeni (AR), ha suscitato interesse nel mondo scientifico per il possibile impiego di terapie anti-androgeniche in questo sottogruppo di neoplasie mammarie. Evidenze pre-cliniche evidenziano inoltre un’iperattivazione della via di segnale mediata da mTOR nei TNBC AR+. Il nostro studio ha voluto valutare l’incidenza di positività di AR e della forma attiva di mTOR (p-mTOR) su 180 TNBC, valutandone la correlazione con le caratteristiche cliniche, patologiche e molecolari, nonché il loro significato prognostico. Pazienti e metodi: La nostra analisi è stata condotta su 180 pazienti con diagnosi di TNBC stadio I-III afferite c/o la Clinica di Oncologia degli Ospedali Riuniti di Ancona tra gennaio 2009 e dicembre 2015. Risultati: AR è risultato espresso nel 24,4% dei casi e non ha mostrato una correlazione prognostica con la sopravvivenza globale (p=0.26) e libera da malattia (p=0.30). L’espressione di AR è risultata più frequentemente associata alla presenza di metastasi ai linfonodi ascellari (p=0.05) e di invasione vascolare (p=0.04). Analogamente i dati preliminari su 98 pazienti non hanno evidenziato un ruolo prognostico di p-mTOR, che è tuttavia risultato significativamente più espresso nei TNBC di piccole dimensioni (p=0.03) con AR-positivi (p=0.04). Conclusioni: AR non sembra avere un significato prognostico nei TNBC. I risultati preliminari su p-mTOR non mostrano un’associazione con la prognosi delle pazienti; tuttavia la presenza di una correlazione significativa tra l’attivazione di mTOR e AR potrebbe rappresentare il presupposto terapeutico per l’utilizzo di farmaci che inducono una doppia inibizione sia su AR che su mTOR con un sinergico effetto anti-proliferativo sulle cellule tumorali.Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. Besides emerging preclinical evidence suggested that TNBC cells seem particularly sensitive to mTOR inhibitors, especially the androgen receptor-positive (AR+) TNBC cell lines. In the present study, we explored the correlation of AR and p-mTOR (the activate form of mTOR) expressions with clinical, pathological and molecular features and their impact on prognosis in early TNBC. Patients and Methods: Between January 2009 and December 2015, all consecutive patients who were diagnosed and completed the treatment of invasive early TNBC at our institution were eligible for this analysis. Results: 180 TNBC patients were included in the analysis. 24.4% of them were AR+. Expression of AR+ was significantly associated with lympho-vascular invasion (p=0.04) and metastases of axillary nodes (p=0.05). Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p=0.30) or overall survival (p=0.26). Of 98 patients, 32.6% of cases were p-mTOR positive. Univariate survival analysis revealed that p-mTOR positivity was not associated with DFS (p=0.74) and OS (p=0.95). p-mTOR positivity was associated with small tumor size (p=0.03) and AR expression (p=0.04). Conclusions: The expression of AR is associated with some biological features of TNBC, such as lympho-vascular invasion and metastasis of axillary nodes; nevertheless the prognostic significance of AR was not documented in our analysis. Of interest, our preliminary results showed the strong correlation between p-mTOR immunostaining and AR positivity, suggesting that may exist a subgroup of TNBC in which the combination of both AR antagonism and mTOR inhibition should have a synergistic effect on cell growth and tumour progression

Metastatic breast cancer mimicking a hilar cholangiocarcinoma: case report and review of the literature

Breast cancer is the most common tumor in women and the first cause of death for malignancy in the female population. Bile ducts are not among the common sites of metastasis from breast cancer; few cases of obstructive jaundice due to metastatic breast cancer have been described in the literature and they mostly resulted from widespread liver metastases that eventually involved the bile ducts. We report an exceptional case of metastatic infiltration of the extrahepatic bile ducts in absence of liver metastases

Three drugs vs two drugs first-line chemotherapy regimen in advanced gastric cancer patients: a retrospective analysis

The definition of the standard chemotherapy regimen for advanced gastric cancer is still a matter of debate. Aim of our analysis was to retrospectively assess whether an intensive, three-drugs, front line approach could be comparable to a sequential (two-drugs front line then second line) in terms of RR (response rate), PFS (progression free survival) and OS (overall survival) in advanced gastric cancer patients in the clinical practice. Patients with metastatic gastric cancer who have received a first-line combination chemotherapy with a two or three-drugs regimen were included in our analysis. We divided our patients into two groups, A and B, based on the first line chemotherapy administered (group A = three drugs; group B = two drugs). A total of 425 patients were eligible for our analysis. 216 patients (50.8 %) received three chemotherapeutic agents (group A) and 209 patients (49.2 %) received a two drugs regimen as first-line combination chemotherapy (group B). RR for group A and B was 44 and 29.6 %, respectively (p = 0.0005), median PFS was 7.3 months in group A and 4.5 months in group B (p = 0.0007). No significant difference was found in terms of OS. The addition of a third drug to a doublet chemotherapy regimen appeared more active in terms of response rate and PFS. However median OS resulted comparable. On this basis, the use of a sequential approach may represent a reasonable strategy for patients unwilling or unable to undergo a more intensive treatment without compromising OS

Long‑responders to anti‑HER2 therapies: A case report and review of the literature

Since the introduction of targeted therapies, prognosis in human epidermal growth factor receptor (HER) 2-positive metastatic breast cancer (MBC) has radically changed. The addition of Pertuzumab to Trastuzumab and standard chemotherapy has further increased patients' overall survival (OS). However, there is no agreement regarding the optimal duration of trastuzumab therapy in selected patients achieving long-term complete remission. In addition, no potential factors of long-term benefit have been identified yet. In the present study, we report the case of a MBC woman who was successfully treated with trastuzumab for over 10 years. At the time of diagnosis (February 2005), she revealed lung, nodal and bone metastases. Therefore, a first-line chemotherapy with Epirubicine and Docetaxel was administered for 6 cycles and then the patient started Trastuzumab plus hormonal therapy until reaching a sensible reduction of mammary lump and disappearance of distant metastases. Following a multidisciplinary evaluation, in November 2006, the patient underwent radical mastectomy and axillary dissection, achieving a complete remission. She continued Trastuzumab until September 2015 (for a total of 156 cycles) when a pleural diffusion was demonstrated. Long-term survival during anti-HER2 treatment remains a rare and optimal situation. Currently, no data exist to support trastuzumab interruption in this setting and collaborative efforts to better analyze the characteristics of long-responder patients are needed. Data regarding prognostic factors in this setting are relatively confusing. Our review reveals that hormonal receptor (HR)-positive disease is associated with a better prognosis, whereas the role of visceral spread differs by single or dual target anti HER2-inhibition. The introduction of Pertuzumab is raising concerns in terms of toxicity and its cost effectiveness. While waiting for novel molecular data and randomized trials, available evidence advocates continuous use of anti-HER2 therapies until disease progression or development of side effects