Excision Repair Cross Complementation Group 1 Single Nucleotide Polymorphisms and Nivolumab in Advanced Non-Small Cell Lung Cancer.

Background: We hypothesized that non-small cell lung cancer (NSCLC) patients with a tumor positive for single nucleotide polymorphisms (SNPs) of the Excision Repair Cross Complementation Group 1 (ERCC-1) gene could be more genetically instable and consequently more responsive to a programmed cell death-1 (PD-1) blockade. Methods: We evaluated the T19007C and C8092A ERCC-1 SNPs by pyrosequencing assay, on tumor specimens from two independent cohorts of patients who relapsed after one or more prior systemic treatments for advanced NSCLC and who received nivolumab (3 mg/kg intravenously every 2 weeks) as part of the Italian Expanded Access Program. We aimed to assess the outcome of enrolled subjects according to the ERCC-1 SNPs status, to evaluate the role of these polymorphisms as putative biomarkers associated with a response/clinical benefit to anti-PD-1 therapies. Results: Of the 45 patients included in the final analysis, 21 (47%) and 16 (36%) were positive for the T19007C and C8092A polymorphic genotype (PG), respectively. In univariate analyses, overall survival (OS) and progression free survival (PFS) were shorter in patients with the T19007C PG, but neither difference achieved statistical significance (P = 0.131 and P = 0.717, respectively). The presence of the C8092A PG was associated with a longer OS and PFS, although statistical significance was only reached for PFS (P = 0.112 and P = 0.025, respectively). These results were confirmed by multivariate analyses. The response rate was only significantly higher in patients with the C8092A PG vs. wild type ERCC-1 (62 vs. 7%, P < 0.001). Conclusions: Results from this hypothesis generating pilot study, provided suggestive evidence that a subgroup of NSCLC patients could benefit differently from nivolumab according to the C8092A ERCC-1 SNP status. However, these data warrant further investigation.

Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial.

PURPOSE: Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor-positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required. PATIENTS AND METHODS: We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points. RESULTS: Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor-positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04). CONCLUSION: Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.

Fludarabine, mitoxantrone and dexamethasone as front-line therapy in elderly patients affected by newly-diagnosed, low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors: results of a phase II study.

About one-third of the cases of non-Hodgkin's lymphomas occur in patients aged 60 years or more. Nevertheless, there are very few data in the literature regarding the optimal therapeutic approach for both aggressive and indolent histologies. Fludarabine-based combination regimens are an effective choice for younger patients affected by low-grade non-Hodgkin's lymphomas, but there is a lack of information about their tolerability and efficacy in older patients. We performed a phase II study to test the efficacy and safety of the combination of Fludarabine, Mitoxantrone and Dexamethasone (FND) in newly-diagnosed, chemo-naive elderly patients affected by low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors. From March 1999 to March 2002, 18 patients were enrolled into the study. All the patients were evaluated for toxicity and response. Neutropenia and thrombocytopenia have been registered as the main toxicities. Thirteen (72%) patients experienced a complete response and 4 (22%) a partial response: the overall response rate was 94%. At a median follow-up of 19 months, the median time for progression-free-survival and the median survival time were not reached yet. The 2-years projected progression-free-survival and overall-survival are 52% and 67% respectively. When administered as first-line treatment to a population of elderly patients affected by high-risk, low-grade non-Hodgkin's lymphomas, FND showed a high efficacy and a good toxicity profile. Our data compare favorably to those reported for the same schedule administered both as first- or second-line therapy in younger patients.