Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial.

Objectives Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB-IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB-IVM1a disease.Patients and methods The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit-risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons.Results Among 249 evaluated patients with stage IIIB-IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; PP<0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments.Conclusion The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated

Relationship of menopausal status and climacteric symptoms to sleep in women undergoing chemotherapy

Goals of workThe goal of this study was to examine the relationship between menopausal symptoms, sleep quality, and mood as measured by actigraphy and self-report prior to treatment and at the end of four cycles of chemotherapy in women with breast cancer.Patients and methodsData on sleep quality (measured using actigraphy and self-report) and mood were collected prior to treatment and 12&nbsp;weeks later at the end of four cycles of chemotherapy in 69 women with newly diagnosed breast cancer. In addition, each filled out the Greene Climacteric Scale. Based on reported occurrence of menses, participants were categorized post hoc into three menopausal status groups: pre-menopausal before and after chemotherapy (Pre-Pre), pre-menopausal or peri-menopausal before and peri-menopausal after chemotherapy (Pre/Peri-Peri), and post-menopausal before and after chemotherapy (Post-Post).Main resultsResults suggested that women within the Pre-Pre group evidenced more fragmented sleep with less total sleep time (TST) after chemotherapy compared to baseline. Compared to the other groups, the Pre-Pre group also experienced less TST and more awakenings before and after chemotherapy. Although the Pre/Peri-Peri group evidenced a greater increase in vasomotor symptoms after chemotherapy, there was no relationship with sleep. All groups evidenced more depressive symptoms after chemotherapy, but depression was not related to measures of sleep.ConclusionsContrary to the study hypothesis, these results suggest that women who are pre-menopausal or having regular menses before and after four cycles of chemotherapy have worse sleep following chemotherapy. Those women who maintain or become peri-menopausal (irregular menses) experience an increase in climacteric symptoms but do not experience an associated worsening of sleep. These results are preliminary and more research is necessary to further explain these findings

Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin

Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities

Safety and efficacy of ipilimumab in melanoma patients who received prior immunotherapy on phase III study MDX010-020

9050 Background: MDX010-020 was a phase III comparison of ipilimumab (Ipi), gp100 vaccine or the combination for advanced melanoma. A subset of patients (pts) received other immunotherapy (IM) for advanced disease prior to receiving Ipi, providing the opportunity to evaluate safety and efficacy of Ipi following IM. A prior analysis has shown that pts receiving prior IL-2 had a similar overall survival (OS) to pts who had not received prior IL-2 [Hodi et al NEJM2010]; we now report expanded results for pts receiving any prior IM (interferons and/or interleukin). Methods: Eligible pts (n=676) had unresectable stage III/IV melanoma and were randomized 3:1:1 to q3 wks x 4 doses of Ipi + gp100 or Ipi + placebo or gp100 + placebo. All Ipi doses were 3 mg/kg i.v. OS was retrospectively analyzed for pts receiving any prior IM; immune-related adverse events (irAEs) during induction were evaluated for pts who received any prior IM (322 pts, 48%) and for pts who received prior IL-2 (154 pts, 23%). Results: Demography and OS are summarized below. irAEs of any grade were reported for 60% (Ipi) and 54% (Ipi + gp100) of pts receiving any prior IM. Those receiving prior IL-2 specifically had 73% (Ipi) and 58% (Ipi + gp100) incidence of any grade irAEs. Incidence was similar for those not receiving prior IM or prior IL-2. Diarrhea, rash, and pruritus were the most common events in all groups. Conclusions: Results for OS in this subgroup analysis were similar for both those receiving any prior IM and those who did not receive prior IM and to the overall 020 population. In addition, safety profiles were similar irrespective of prior immunotherapy. Clinical trial information: NCT00094653. [Table: see text