Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With Somatic NF2 Mutations.

PURPOSE: Patients with progressive or recurrent meningiomas have limited systemic therapy options. Focal adhesion kinase (FAK) inhibition has a synthetic lethal relationship with NF2 loss. Given the predominance of NF2 mutations in meningiomas, we evaluated the efficacy of GSK2256098, a FAK inhibitor, as part of the first genomically driven phase II study in recurrent or progressive grade 1-3 meningiomas. PATIENTS AND METHODS: Eligible patients whose tumors screened positively for NF2 mutations were treated with GSK2256098, 750 mg orally twice daily, until progressive disease. Efficacy was evaluated using two coprimary end points: progression-free survival at 6 months (PFS6) and response rate by Macdonald criteria, where PFS6 was evaluated separately within grade-based subgroups: grade 1 versus 2/3 meningiomas. Per study design, the FAK inhibitor would be considered promising in this patient population if either end point met the corresponding decision criteria for efficacy. RESULTS: Of 322 patients screened for all mutation cohorts of the study, 36 eligible and evaluable patients with NF2 mutations were enrolled and treated: 12 grade 1 and 24 grade 2/3 patients. Across all grades, one patient had a partial response and 24 had stable disease as their best response to treatment. In grade 1 patients, the observed PFS6 rate was 83% (10/12 patients; 95% CI, 52 to 98). In grade 2/3 patients, the observed PFS6 rate was 33% (8/24 patients; 95% CI, 16 to 55). The study met the PFS6 efficacy end point both for the grade 1 and the grade 2/3 cohorts. Treatment was well tolerated; seven patients had a maximum grade 3 adverse event that was at least possibly related to treatment with no grade 4 or 5 events. CONCLUSION: GSK2256098 was well tolerated and resulted in an improved PFS6 rate in patients with recurrent or progressive NF2-mutated meningiomas, compared with historical controls. The criteria for promising activity were met, and FAK inhibition warrants further evaluation for this patient population.

A Novel Graphic Medicine Curriculum for Resident Physicians: Boosting Empathy and Communication through Comics.

Curricular design that addresses residency physician competencies in communication skills and professionalism remains a challenge. Graphic Medicine (GM) uses comics, a medium combining text and images, to communicate healthcare concepts. Narrative Medicine, in undergraduate medical education, has limited reported usage in Graduate Medical Education (GME). Given the time constraints and intensity of GME, we hypothesized that comics as a form of narrative medicine would be an efficient medium to engage residents.The authors created a novel curriculum to promote effective communication and professionalism, focusing on empathy, compassion and cultural competency. A four-week curriculum was delivered in a neurology residency program. Excerpts from non-fiction graphic memoirs about neurological conditions were read, discussed, and paired with prompt-driven drawing exercises. Qualitative surveys were used to assess acceptability of comics, usefulness of comics to convey patient illness experience, and perception of patient needs for physician-patient communication.Ninety-seven percent of residents reported the sessions were a good use of their time. Residents identified new symptoms of neurologic disorders, articulated patient communication needs, and expressed increased empathy after participation. Residents participated in drawing exercises, but these were not formally analyzed. Graphic medicine is a well received format that may build communication skills and increase empathy.

Treatment Considerations for Patients with Unresectable Metastatic Melanoma Who Develop Pembrolizumab-Induced Guillain-Barré Toxicity: A Case Report.

Immunotherapy has improved outcomes in many malignancies, most notably in melanoma, lung cancer, and bladder cancer. Understanding the side effects associated with these medications is an important part of managing our patients. Although fatigue, rash, and diarrhea are commonly reported side effects, it is important to be cognizant of rarer ones, such as neuropathy. Amongst the different neurological toxicities that have been reported in the literature, Guillain-Barré-like neuropathies are quite rare. However, the occurrence of such neuropathies in a patient can be life threatening. The problem this poses in treating cancers such as melanoma is that it eliminates an effective class of medication available to the patient, which can ultimately affect their prognosis. We present a case of a 65-year-old female with unresectable metastatic melanoma who developed Guillain-Barré-like neuropathy after two doses of pembrolizumab. Her clinical course was complicated by three separate hospitalizations over 3 months due to recurring bouts of neuropathy, which resulted in a significant decline in performance status and delay in subsequent treatment of her melanoma. Her prolonged recovery eventually resulted in progression of her melanoma nearly 1 year later, while off therapy. Instead of discontinuing immunotherapy completely, she agreed to a re-challenge with ipilimumab. After one dose, her melanoma regressed and continues to show a sustained response nearly 1 year after treatment without any signs of relapse in her neuropathy. Guillain-Barré toxicity resulting from immune checkpoint inhibition poses a difficult challenge to an oncologist who is determining the next line of treatment for patients with unresectable metastatic melanoma that have progressed while off therapy and who have no targetable mutations. Our case raises the question of whether a re-challenge with a different class of immunotherapy agent is a reasonable option.

A clinical care pathway to improve the acute care of patients with glioma.

BACKGROUND: Patients with glioma are at increased risk for tumor-related and treatment-related complications. Few guidelines exist to manage complications through supportive care. Our prior work suggests that a clinical care pathway can improve the care of patients with glioma. METHODS: We designed a quality improvement (QI) project to address the acute care needs of patients with gliomas. We formed a multidisciplinary team and selected 20 best-practice measures from the literature. Using a plan-do-study-act framework, we brainstormed and implemented various improvement strategies starting in October 2013. Statistical process control charts were used to assess progress. RESULTS: Retrospective data were available for 12 best practice measures. The baseline population consisted of 98 patients with glioma. Record review suggested wide variation in performance, with compliance ranging from 30% to 100%. The team hypothesized that lack of process standardization may contribute to less-than-ideal performance. After implementing improvement strategies, we reviewed the records of 63 consecutive patients with glioma. The proportion of patients meeting criteria for 12 practice measures modestly improved (65% pre-QI; 76% post-QI, P > .1). Unexpectedly, a higher proportion of patients were readmitted within 30 days of hospital discharge (pre-QI: 10%; post-QI: 17%, P > .1). Barriers to pathway development included difficulties with transforming manual measures into electronic data sets. CONCLUSIONS: Creating evidence-based clinical care pathways for addressing the acute care needs of patients with glioma is feasible and important. There are many challenges, however, to developing sustainable systems for measuring and reporting performance outcomes overtime.