Olaparib monotherapy in patients with advanced relapsed ovarian cancer and a germline BRCA1/2 mutation: a multistudy analysis of response rates and safety.

BACKGROUND: The PARP inhibitor olaparib (Lynparza™) demonstrates antitumor activity in women with relapsed ovarian cancer and a germline BRCA1/2 mutation (gBRCAm). Data from olaparib monotherapy trials were used to explore the treatment effect of olaparib in patients with gBRCAm ovarian cancer who had received multiple lines of prior chemotherapy. PATIENTS AND METHODS: This analysis evaluated pooled data from two phase I trials [NCT00516373 (study 2); NCT00777582 (study 24)] and four phase II trials [NCT00494442 (study 9); NCT00628251 (study 12); NCT00679783 (study 20); NCT01078662 (study 42)] that recruited women with relapsed ovarian, fallopian tube or peritoneal cancer. All patients had a documented gBRCAm and were receiving olaparib 400 mg monotherapy twice daily (capsule formulation) at the time of relapse. Objective response rate (ORR) and duration of response (DoR) were evaluated using original patient outcomes data for patients with measurable disease at baseline. RESULTS: Of the 300 patients in the pooled population, 273 had measurable disease at baseline, of whom 205 (75%) had received ≥3 lines of prior chemotherapy. In the pooled population, the ORR was 36% [95% confidence interval (CI) 30-42] and the median DoR was 7.4 months (95% CI 5.7-9.1). The ORR among patients who had received ≥3 lines of prior chemotherapy was 31% (95% CI 25-38), with a DoR of 7.8 months (95% CI 5.6-9.5). The safety profile of olaparib was similar in patients who had received ≥3 lines of prior chemotherapy compared with the pooled population; grade ≥3 adverse events were reported in 54% and 50% of patients, respectively. CONCLUSION: Durable responses to olaparib were observed in patients with relapsed gBRCAm ovarian cancer who had received ≥3 lines of prior chemotherapy. CLINICALTRIALSGOV: NCT00516373; NCT00494442; NCT00628251; NCT00679783; NCT00777582; NCT01078662.

A phase II trial of carbetimer for the treatment of colorectal cancer. A trial of the Northern California Oncology Group.

Carbetimer (carboxyimamidate) was administered at a dose of 6,500 mg/m2/day intravenously for 5 consecutive days to 14 patients with measurable metastatic or recurrent colorectal cancer in a single institution phase II study of the Northern California Oncology Group. A total of 38 cycles of therapy were administered; nine patients completed at least three cycles of treatment. No partial or complete responses were observed. One patient did have a greater than 50% response in the liver while developing new retroperitoneal lymphadenopathy and is considered a nonresponder. Carbetimer was well tolerated with elevations of calcium from 10.2 to 12.5 mg/dl in nine patients, prolongation of prothrombin time and partial thromboplastin time in 14 patients, proteinuria in 10 patients, dizziness in six patients, nausea in two patients, and venous pain during infusion in three patients. Myelosuppression was not observed. Carbetimer at this dose and schedule is inactive in the treatment of colorectal cancer.

Immunophenotypic differences between plasmacytoma/multiple myeloma and immunoblastic lymphoma.

Four cases of plasmacytoma (PC), six cases of multiple myeloma (MM), and nine cases of immunoblastic lymphoma (IL) of B-cell phenotype were studied with a large panel of monoclonal antibodies applied to frozen tissue sections. There were no significant differences in the immunophenotypes of plasmacytomas and multiple myelomas. However, significant immunophenotypic differences were noticed between the plasmacytoma/multiple myeloma cases (PC/MM) and the immunoblastic lymphoma specimens. The PC/MM cases characteristically stained with alpha (or gamma) and T10 and did not usually stain with mu, leukocyte common antibodies, certain B-lineage antibodies (B1, T015, 4G7, 6A4), or Ia. In contrast, IL sections usually did not stain with alpha or T10 and generally did stain with mu (or gamma), leukocyte common antibodies, B-lineage antibodies, and Ia. Ki-67, an antibody to proliferating cells, stained significantly fewer cells in PC/MM than in IL and stained significantly fewer cells that had a good clinical outcome. We conclude that although no one antibody is useful in distinguishing PC/MM from IL, the application of a panel of antibodies may be helpful in making this distinction. The prognosis may correlate with the numbers of proliferating cells as measured by reactivity with Ki-67.

Small cell lung carcinoma in the elderly.

Twenty-four patients over the age of 70 with small cell cancer of the lung were studied retrospectively. Ninety-two per cent of these patients had other concurrent medical disorders; 58 per cent had cardiac disease and 25 per cent had a second malignancy. The median survival of 20 treated patients was ten months, and the one-year survival was 30 per cent. Such elderly patients with multiple medical problems can benefit from combination chemotherapy.