Enzo Veltri

Eribulin Mesylate in Pretreated Breast Cancer Patients: A Multicenter Retrospective Observational Study

Background: Eribulin was recently approved in patients progressing after being treated with anthracyclines and taxanes and after two or more chemotherapy lines for advanced disease. Objectives: This multicenter observational retrospective study was performed in order to evaluate activity and tolerability of eribulin in real-world patient population. Methods: 133 advanced breast cancer patients pretreated with ≥ 2 chemotherapy lines for metastatic disease were retrospectively enrolled in the observational trial in 11 italian cancer centres. Results: A median of 5 cycles of eribulin (range, 1-15) were administered. Twenty-eight partial responses were observed, for an overall response rate of 21.1% (95%CI,14.1-28.0). A stable disease was recorded in 57 patients (42.8%), and a clinical benefit (response or stable disease lasting ≥ six months) was observed in 51 patients (38.3%, 95%CI, 30.1-46.6). The subgroup analysis showed that a significant improvement in term of partial response and clinical benefit was achieved when eribulin was administered in HER-2 negative tumors (p=0.01 and p=0.004, respectively) and when it is given as third-line (p=0.09 and p=0.02, respectively). Toxicity was manageable; fatigue is the most common side effect observed, usually of low-grade, and clearly cumulative-dose related. Conclusions: In this retrospective, observational analysis eribulin confirmed its efficacy and manageable tolerability even in real-world population and in heavily pretreated patients.

Biosimilar medicines in oncology: single-center experience with biosimilar G-CSF

AIMS A biosimilar medicine is one with proven similarity to a reference biological product for which the patent has expired and whose active ingredient is produced or derived from a living organism. Recombinant granulocyte colony-stimulating growth factors (G-CSF) are used for the prophylaxis of febrile neutropenia. MATERIALS & METHODS In this observational, single-center study, a total of 48 patients with solid tumors were treated with a new biosimilar G-CSF (Zarzio(®)) for 4-14 days from the day following the end of chemotherapy. RESULTS Between October 2010 and July 2011, biosimilar G-CSF was administered as primary prophylaxis in 37 patients and as secondary prophylaxis in 11 patients in our clinic. The median length of G-CSF administration was 7 days (range: 1-12 days). Three cases of febrile neutropenia were reported: two in patients with prostate adenocarcinoma and one in a patient with pulmonary squamous cell carcinoma and multiple secondary skeletal lesions. These patients were treated with antibiotics and improved within 24 h without the need for hospitalization. Nonfebrile grade 4 neutropenia was observed in a further six patients. CONCLUSION Our experience indicates that the use of biosimilar G-CSF is safe and effective at reducing neutropenic complications in patients with solid tumors and may be associated with cost savings.

Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of K-ras mutation

Background Bevacizumab plus chemotherapy prolongs progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC). Although there is strong evidence to suggest that the mutational status of the K-ras oncogene has a role as a predictive factor for activity in patients treated with cetuximab and panitumumab, few data have been obtained in patients treated with bevacizumab. We conducted an additional retrospective analysis to investigate the prognostic value of K-ras mutation relative to mCRC first-line treatment with bevacizumab. Materials and methods A total of 108 patients were retrospectively reviewed. K-ras status was assessed in the overall population by sequencing. Statistical association for PFS and OS was analyzed using the Kaplan–Meier method, and the prognostic role of K-ras was determined using the logrank test. Results Median PFS was 10 months both for patients with wild-type (WT) K-ras and mutated (MT) K-ras (hazard ratio [HR] 0.94, P=0.75); neither difference in median OS was significant (27 months WT K-ras versus 26 months MT K-ras, HR 0.92; P=0.70). A further analysis was carried out in the two groups according to metastatic sites. No statistically significant difference in terms of PFS and OS was demonstrated between WT K-ras and MT K-ras with liver metastases only and in those with extrahepatic disease. Conclusion Although further study is required, our results seem to confirm that K-ras mutation does not have a prognostic role in mCRC patients receiving first-line treatment with bevacizumab.

Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice

AIM The effect of KRAS status on response to bevacizumab plus chemotherapy in metastatic colorectal cancer is still unclear. We aimed to evaluate the overall clinical response to such a therapy in clinical practice and assess the role of KRAS status on therapy response. PATIENTS & METHODS This was a retrospective study enrolling 108 metastatic colorectal cancer patients. KRAS mutation analysis was performed by PCR. RESULTS Overall, 41.7% of patients had stable disease, 39.8% a partial response, 3.7% a complete response and 14.8% disease progression. Both clinical benefit and objective response rate tended to be higher in patients with only hepatic metastases than those with extrahepatic or multiple metastases. Response to therapy would appear to be independent of KRAS status, but larger studies are needed. CONCLUSION Bevacizumab plus chemotherapy provides clinical benefit and objective response rate in patients with metastatic colorectal cancer independently of KRAS expression, especially in those patients with only liver metastases.

Biomolecular, biochemical, and radiologic evaluation and safety of chemotherapy with bevacizumab in treatment of patients affected by mCRC.

e14140 Background: Bevacizumab (BEV) combined with chemotherapy prolongs PFS and OS in treatment of mCRC regardless of KRAS status. This study investigated statistical significance of BEV clinical benefit (CB) in treatment of mCRC according to KRAS status and metastatic sites.We evaluated timing of response through correlation between tumor markers values (MKS) and clinical responses. Most severe toxicities were observed. METHODS 108 patients were treated with first-line Folfiri or FolFoX and BEV. KRAS status was detected. Before therapy patients were investigated with CT scan and with blood sample to define MKS; MKS after 2 months of chemotherapy and CT scan after 3 months were performed. Statistical analysis has benefited from chi-square test. RESULTS Overall response rate (RR) of 42% and CB of 82% were obtained, with correlation between MKS and clinical response of 90%. 49% of population presented only hepatic metastases while 51% showed multiple metastatic sites. RR in exclusive hepatic metastatic group was 48% vs 35% multiple metastatic sites (p=0.15), CB was 90% vs 71% respectively (p=0.01). KRAS mutations were investigated in 100 patients. 65 patients were wild-type (wt 65%) while 35 patients were mutated (mut 35%). RR in wt group was 51% vs 29% in mut (p=0.03), while CB was 86% vs 80% respectively (p=0.42). Correlation between MKS and clinical response was 91% in wt group vs 93% in mut. 72 patients (66%) experienced any grade toxicities. Most common G3-G4 toxicities were neutropenia (16%), diarrhea (4%) and vomiting (2%). G1-G2 BEV toxicities were bleeding (13%), hypertension (10%), deep vein thrombosis (5%), proteinuria (2%) and pulmonary embolism (1%); no G3-G4 toxicities were showed. CONCLUSIONS RR in KRAS groups was different with an advantage, statistical significant, in KRAS wt, but this difference does not observe in CB. BEV provides significant RR and CB after short time of treatment and MKS are optimal parameters of early clinical response. BEV provides statistical significant CB in patients with only hepatic metastases vs patients with multiple metastatic sites. Treatment with BEV was well tolerated.