Safety and efficacy of sunitinib in patients from Italy with metastatic renal cell carcinoma: final results from an expanded-access trial.

OBJECTIVES: Patients with metastatic renal cell carcinoma (mRCC) received sunitinib in a global expanded-access program (EAP). Here, we report the efficacy and safety results for the EAP subpopulation in Italy. METHODS: Patients ≥18 years old with previously treated or treatment-naïve mRCC received oral sunitinib 50 mg/day on a 4-weeks-on/2-weeks-off schedule. Tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors). Safety was regularly assessed. RESULTS: A total of 521 patients participated, including 40% aged ≥65 years, 11% with an Eastern Cooperative Oncology Group performance status ≥2, 14% with non-clear cell RCC, and 11% with brain metastases. The median treatment duration and posttreatment follow-up were 7.4 and 12.3 months, respectively. The objective response rate was 12%, and the median progression-free and overall survival was 9.1 and 27.2 months, respectively. 514 patients (99%) discontinued treatment; reasons included death (17%), nonresponse (46%), or adverse events (AEs; 13%). The most common any-grade treatment-related AEs were asthenia (44%, plus 15% reporting fatigue), thrombocytopenia and stomatitis (both 37%), diarrhea (36%), mucosal inflammation (29%), hypertension (26%), and dysgeusia (25%). The most common grade 3/4 treatment-related AEs were thrombocytopenia (10%), asthenia (9%, plus 3% reporting fatigue), neutropenia, stomatitis (both 6%), and hypertension (5%). CONCLUSION: In a large population of Italian mRCC patients, sunitinib had a manageable safety profile and encouraging efficacy.

Maintenance single-agent bevacizumab or observation after first-line chemotherapy in patients with metastatic colorectal cancer: a multicenter retrospective study.

The addition of bevacizumab to standard chemotherapy has improved progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in both first- and second line treatment, but the role of maintenance bevacizumab remains controversial. The association of various clinical factor and survival was examined in this retrospective cohort analysis. The clinical data from 220 previously untreated patients with mCRC, not progressive at the end of standard chemotherapy plus bevacizumab, were collected and analyzed. Patients were classified into two subgroups: those given with maintenance bevacizumab: "maintenance bevacizumab cohort (n = 118; MB)", and those discontinuing bevacizumab as a result of physician's or patient's decision: "no maintenance bevacizumab cohort (n = 102; noMB)". The baseline factors were well balanced between the study subgroups. Median PFS and OS for the general population was 10 months (range 7-15) and 22.5 months (range 18-26), respectively. Median PFS was 13 and 8 months in the BM and noBM cohorts, respectively (p < 0.0001). In the multivariate analysis, maintenance therapy resulted independently associated with improved PFS (HR 1.73; p < 0.001), but only objective response (OR) after first-line chemotherapy was associated with improved OS. Maintenance chemotherapy cannot be considered a standard of care after induction chemotherapy for mCRC, because the optimal balance between efficacy and safety of maintenance therapy remains a significant challenge. The results of our retrospective study suggest that maintenance therapy with bevacizumab is a safe and valuable option, particularly in those patients achieving an objective response after first-line chemotherapy.

Peripheral lymphocyte subset counts predict antibody response after SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients: Results from the Vax-On-Profile study.

BACKGROUND: The adaptive immune response following COVID-19 vaccination is essential for humoral immunogenicity and clinical protection against symptomatic infections. We present the results of circulating lymphocyte profiling and their correlation with antibody response in cancer patients tested serologically six months after receiving a two-dose schedule of mRNA-BNT162b2 vaccine. METHODS: Absolute counts of lymphocyte subsets were determined using peripheral blood immunophenotyping. We collected samples for flow cytometry analysis alongside quantitative detection of IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S1). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. RESULTS: 311 patients were evaluable for lymphocyte profiling and serologic testing. A preliminary multivariate analysis revealed that cytotoxic chemotherapy was the most consistent factor associated with lower counts of all lymphocyte subpopulations. T helper and B cells were found to be useful in predicting the occurrence of a positive seroconversion response using ROC curve analysis. A significant positive linear correlation was shown when anti-RBD-S1 IgG titers were compared to these lymphocyte subset counts. Univariate analysis indicated that antibody titers and seroconversion rates were significantly improved in the high-level T and B cell subgroups. Multivariate analysis confirmed these significant interactions, as well as the negative predictive value of immunosuppressive corticosteroid therapy. CONCLUSIONS: These findings suggest that simple and widely available peripheral counts of T helper and B cells correlate with humoral response to mRNA-BNT162b2 vaccine in actively treated cancer patients. Upon validation, our results could provide additional insights into the predictive assessment of vaccination efficacy.

Capecitabine and celecoxib as second-line treatment of advanced pancreatic and biliary tract cancers.

OBJECTIVE: An increasing number of patients with advanced pancreatic or biliary tract cancer who progress after a gemcitabine-containing regimen are candidates for further chemotherapy. We therefore evaluated a fully oral regimen of capecitabine and celecoxib (CapCel) as second-line treatment in these patients. METHODS: Thirty-five patients with documented progressive disease after first-line treatment were enrolled. Capecitabine was administered at a dose of 1,000 mg/m(2) b.i.d. for 2 consecutive weeks followed by 1 week of rest; celecoxib was given continuously at 200 mg b.i.d. Progression-free survival at 3 months was the primary study endpoint. RESULTS: The CapCel combination was associated with an overall response rate of 9% and median survival duration of 19 weeks. Sixty percent of patients were free from progression 3 months after the start of treatment. Multivariate analysis identified a positive clinical benefit response and a decline in CA 19.9 serum levels >25% compared with baseline levels as independent predictors of prolonged survival. The treatment protocol was well tolerated with negligible hematological toxicity. The most common grade 3 non-hematological toxicities were hypertransaminasemia, diarrhea and asthenia. CONCLUSIONS: The CapCel combination is a safe treatment option with moderate activity in patients with pancreatic/biliary tract cancer after failure of a previous gemcitabine-containing regimen.

Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study.

OBJECTIVES: The influence of age (<70 years and ≥70 years) was retrospectively studied on the quality of life (QoL), incidence of side effects (including skin reactions) and efficacy of chemotherapy plus cetuximab in patients with KRAS wild type (WT) metastatic colorectal cancer (mCRC). METHODS: 225 patients of the Observed study (PS 0-1) were retrieved based on age (< 70 and ≥70 years) and evaluated through EORTC QLQ-C30 and DLQI questionnaires. RESULTS: The two patient groups (141 < 70 and 84 ≥ 70 years, respectively) were balanced with no differences in any of the clinical and pathological characteristics considered. Both groups underwent similar type of first-line chemotherapy plus cetuximab, treatment duration and compliance. Cetuximab therapy caused similar incidence of side effects and impact on QoL in older and younger patients. No difference was observed in progression free survival (PFS) and in disease control rates between the two patient populations. Median overall survival (OS) was higher in patients <70 (27 months, 95% CI: 22.7-31.27) than in patients ≥70 (19 months, 95% CI: 14.65-23.35) (p = 0.002), which is likely due to higher proportions of metastatic resection (27.0% vs 8.3%; p = 0.001) and utilization of second-line therapy in younger group (58.9% vs 42.9%; p = 0.028). CONCLUSION: The current data suggest that fit older patients with mCRC can be safely treated with a cetuximab-based therapy, as QoL and safety profile do not seem to be affected by age. In addition, age did not impact the choice of chemotherapy to be associated to cetuximab and treatment compliance.

Observational study on quality of life, safety, and effectiveness of first-line cetuximab plus chemotherapy in KRAS wild-type metastatic colorectal cancer patients: the ObservEr Study.

Cetuximab improves efficacy when added to chemotherapy for metastatic colorectal cancer (mCRC). Effective management of skin reactions from cetuximab improves quality of life (QoL), and treatment compliance in clinical trials. No data are available from real-world settings. The ObservEr observational, multicenter, prospective study evaluated QoL, the incidence of skin reactions, and management of chemotherapy plus cetuximab in first-line for mCRC. The primary endpoint was QoL measured with the Dermatology Life Quality Index (DLQI) and EORTC QLQ-C30. Secondary endpoints were the incidence of skin and serious adverse events, median overall and progression-free survival, tumor response, and resection rates. Between May 2011 and November 2012, 228 patients with KRASwt mCRC were enrolled at 28 Italian centers, 225 evaluable, median age 65 years. QoL did not change during treatment and was not affected by the choice of prophylactic or reactive skin management. The incidence of cetuximab-specific grade ≥3 skin reactions was 14%, with no grade 4/5 events. Skin reactions correlated with survival (P = 0.016), and their incidence was influenced by chemotherapy regimen (oxaliplatin vs. irinotecan-Incidence rate ratio [IRR] 1.72, P < 0.0001) and gender (male vs. female-IRR 1.38, P = 0.0008). Compliance at first postbaseline evaluation was 97.75%. Median overall survival was 23.6 months, median progression-free survival 8.3 months. Cetuximab plus chemotherapy did not compromise QoL in the routine clinical setting when patients receive close monitoring plus prophylactic or reactive management of skin reactions. We observed the same correlation between overall survival (OS) and skin reactions reported in controlled clinical trials, also in this setting.

Epirubicin and docetaxel as first-line treatment for hormonal receptor positive metastatic breast cancer: the predictive value of luminal subtype: a retrospective cohort analysis.

BACKGROUND: We retrospectively evaluated the efficacy of first-line epirubicin and docetaxel in patients with metastatic, hormonal receptor (HR)-positive, and human epidermal growth factor receptor-2-negative breast cancer. A subgroup analysis evaluated the predictive value of immunohistochemistry-defined luminal subtype. METHODS: We included patients with at least one visceral and measurable site of metastatic disease. Patients were grouped as luminal A (HR(+) and Ki67<13%) or luminal B (HR(+) and Ki67>13%). RESULTS: Forty-four patients were entered and prognostic variables were similar between the subgroups. Luminal B patients achieved higher objective response rate than luminal A (69% versus 19%; P = 0.001), longer time to progression (12.2 months versus 8.6 months; P = 0.039), and longer overall survival (24.6 months versus 19.5 months; P = 0.041). The multivariate analysis confirmed the predictive value of luminal B subtype for longer time to progression. CONCLUSIONS: Identification by Ki67 labelling index of human epidermal growth factor receptor-2-negative luminal A could predict a substantial benefit from systemic chemotherapy. Endocrine therapy would be the most appropriate therapy for luminal A tumours.