Phase IIa Study of SurVaxM Plus Adjuvant Temozolomide for Newly Diagnosed Glioblastoma.

PURPOSE: Despite intensive treatment with surgery, radiation therapy, temozolomide (TMZ) chemotherapy, and tumor-treating fields, mortality of newly diagnosed glioblastoma (nGBM) remains very high. SurVaxM is a peptide vaccine conjugate that has been shown to activate the immune system against its target molecule survivin, which is highly expressed by glioblastoma cells. We conducted a phase IIa, open-label, multicenter trial evaluating the safety, immunologic effects, and survival of patients with nGBM receiving SurVaxM plus adjuvant TMZ following surgery and chemoradiation (ClinicalTrials.gov identifier: NCT02455557). METHODS: Sixty-four patients with resected nGBM were enrolled including 38 men and 26 women, in the age range of 20-82 years. Following craniotomy and fractionated radiation therapy with concurrent TMZ, patients received four doses of SurVaxM (500 µg once every 2 weeks) in Montanide ISA-51 plus sargramostim (granulocyte macrophage colony-stimulating factor) subcutaneously. Patients subsequently received adjuvant TMZ and maintenance SurVaxM concurrently until progression. Progression-free survival (PFS) and overall survival (OS) were reported. Immunologic responses to SurVaxM were assessed. RESULTS: SurVaxM plus TMZ was well tolerated with no serious adverse events attributable to SurVaxM. Of the 63 patients who were evaluable for outcome, 60 (95.2%) remained progression-free 6 months after diagnosis (prespecified primary end point). Median PFS was 11.4 months and median OS was 25.9 months measured from first dose of SurVaxM. SurVaxM produced survivin-specific CD8+ T cells and antibody/immunoglobulin G titers. Apparent clinical benefit of SurVaxM was observed in both methylated and unmethylated patients. CONCLUSION: SurVaxM appeared to be safe and well tolerated. The combination represents a promising therapy for nGBM. For patients with nGBM treated in this manner, PFS may be an acceptable surrogate for OS. A large randomized clinical trial of SurVaxM for nGBM is in progress.

A new reality: long-term survivorship with a malignant brain tumor.

PURPOSE/OBJECTIVES: To explore the survivor experience of adults who have been diagnosed three years or longer with a primary malignant brain tumor (PMBT). RESEARCH APPROACH: Qualitative using a biographical narrative approach. SETTING: Six sites across the United States. PARTICIPANTS: Survivors of PMBTs (N = 35) and their family caregivers (N = 35). METHODOLOGIC APPROACH: Using a semistructured interview guide, survivors and caregivers were interviewed individually about their lives before and since the PMBT diagnosis. Thematic analysis was performed to identify themes. FINDINGS: Stability in survivor lives disintegrated as a result of the changes experienced related to the tumor and its treatment. Those changes were profound and ultimately contributed to multiple losses in key areas of their lives. Over time, living with the diagnosis and its consequences required survivors and their caregivers to adapt to the new reality of their lives. Through the process of becoming a survivor, individuals were able to take back control of their lives. Adaptation required survivors to use internal and external resources as ways of coping with their new reality. CONCLUSIONS: People with PMBTs require support as they adapt to losses and changes that impact their lives. Assessment of specific changes that impact survivors' lives may be useful in guiding type of support given. Symptom management and mobilization of internal and external resources may lessen the life-changing impact. INTERPRETATION: Nurses should capture symptom meaning during assessments and expand assessments to include social support systems. Instituting measures that facilitate survivor independence may lessen the impact of disability. The significance of symptom worsening over time requires additional research. KNOWLEDGE TRANSLATION: Restoring self-worth and taking control of their lives are critical concerns for survivors of PMBTs.