Purpose Trop-2, expressed in most solid cancers, may be a target for antibody-drug conjugates (ADCs) in non-small-cell lung cancer (NSCLC). We studied sacituzumab govitecan (IMMU-132), a Trop-2 ADC, for the targeting of SN-38. Patients and Methods We evaluated IMMU-132 in a single-arm multicenter trial in patients with pretreated metastatic NSCLC who received either 8 or 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end points were safety and objective response rate (ORR). Progression-free survival and overall survival were secondary end points. Results Fifty-four patients were treated. In the response-assessable study population (n = 47), which had a median of three prior therapies (range, two to seven), the ORR was 19%; median response duration, 6.0 months (95% CI, 4.8 to 8.3 months); and clinical benefit rate (complete response + partial response + stable disease ≥ 4 months), 43%. ORR in the intention-to-treat (ITT) population was 17% (nine of 54). Responses occurred with a median onset of 3.8 months, including patients who had relapsed or progressed after immune checkpoint inhibitor therapy. Median ITT progression-free survival was 5.2 months (95% CI, 3.2 to 7.1 months) and median ITT overall survival, 9.5 months (95% CI, 5.9 to 16.7 months). Grade 3 or higher adverse events included neutropenia (28%), diarrhea (7%), nausea (7%), fatigue (6%), and febrile neutropenia (4%). One patient developed a transient immune response, despite patients receiving a median of 10 doses. More than 90% of 26 assessable archival tumor specimens were highly positive (2+, 3+) for Trop-2 by immunohistochemistry, which suggests that Trop-2 is not a predictive biomarker for response. Conclusion IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this disease and in other patients with Trop-2-expressing tumors.

We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis ( = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections. Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. .

Summary Sera from 182 newly diagnosed breast cancer patients were assayed for antibodies to p53 using an enzyme-linked immunosorbent assay (ELISA) method, and antibodies were detected in 48 (26%) compared with 1 out of 76 (1.3%) normal control volunteers (P= 0.0001). In breast cancer patients, autoantibodies were found in all stages of disease progression: carcinoma in situ, primary invasive breast cancer and in metastatic disease. In the subset of patients in whom sequential sera were assessed over a 6 month period, changes in the p53 antibody titres were observed. The presence of antibodies to p53 correlated positively with high histological grade (P = 0.0012) and a history of second primary cancer (six positive out of eight cases). The incidence of autoantibodies was lower in those patients with a first-degree relative with breast cancer (P = 0.046). Out of 68 patients, there was a significant correlation between positive p53 autoantibody status and the detection of p53 protein in the tissue sections by immunocytochemistry (P = 0.002). In the seronegative patients, positive p53 tumour staining was strongly associated with a family history of breast cancer (P = 0.009). The p53 protein overexpressed in heritable breast cancers may therefore be less immunogenic. The presence of p53 autoantibodies provides important additional information to immunochemistry and may identify patients with aggressive histological types of breast cancer.

Background. The control of diabetes mellitus depends on several factors that also include individual lifestyles. We assessed glycaemic control status and self-management behaviours that may influence glycaemic control among diabetic outpatients. Methods. This cross-sectional study among 198 consenting randomly selected patients was conducted at the University Teaching Hospital diabetic clinic between September and December 2013 in Lusaka, Zambia. A structured interview schedule was used to collect data on demographic characteristics, self-management behaviours, and laboratory measurements. Binary logistic regression analysis using IBM SPSS for Windows version 20.0 was carried out to predict behaviours that were associated with glycaemic control status. Results. The proportion of patients that had good glycaemic control status (HbA1c≤ 48 mmol/mol) was 38.7% compared to 61.3% that had poor glycaemic control status (HbA1c≥ 49 mmol/mol). Adherence to antidiabetic treatment and fasting plasma glucose predicted glycaemic control status of the patients. However, self-blood glucose monitoring, self-blood glucose monitoring means and exercise did not predict glycaemic control status of the patients.  Conclusion. We find evidence of poor glycaemic control status among most diabetic patients suggesting that health promotion messages need to take into account both individual and community factors to promote behaviours likely to reduce nonadherence.