Comparison of Oncologist and Model Estimates of Risk for Hospitalization During Systemic Therapy for Advanced Cancer.

PURPOSE: A validated risk model with inputs of pretreatment sodium and albumin can identify patients at risk for hospitalization during cancer treatment. We evaluated how the model compares with risk estimates from treating oncologists. METHODS: We evaluated the 30-day risk of hospitalization or death in patients starting palliative-intent systemic therapy for solid tumor malignancy. For each patient, we prospectively recorded categorical estimates of 30-day hospitalization risk (bottom third, middle third, top third) generated by a treating oncologist and by the two-variable model; a third hybrid risk estimate represented a composite of the oncologist and model risk assessments. We analyzed the agreement of oncologist and model-based risk estimates and compared discrimination, sensitivity, and specificity of each risk assessment method. RESULTS: We collected oncologist, model, and hybrid estimates of hospitalization risk for 120 patients. The 30-day rate of hospitalization or death was 20%. There was minimal agreement between oncologist and model risk estimates (weighted kappa = 0.27). The c-statistic (a measure of discrimination) was 0.69 (95% CI, 0.57 to 0.81) for the clinician assessment, 0.77 for the model assessment (CI, 0.67 to 0.86; P = .24 compared with the oncologist assessment), and 0.79 for the hybrid assessment (CI, 0.69 to 0.90; P = .007 compared with the oncologist assessment). Sensitivity and specificity of the high-risk categorization did not differ significantly between the oncologist and model assessments; the hybrid assessment was significantly more sensitive (P = .02) and less specific (P = .03) than the oncologist assessment. CONCLUSION: A model with inputs of pretreatment sodium and albumin improves oncologists' predictions of hospitalization risk during cancer treatment.

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 retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL.

Venetoclax (VEN) is approved for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) as monotherapy (VENmono) or in combination with rituximab. Whether VEN plus anti-CD20 (VENcombo) is superior to VENmono is unknown. We conducted a multicenter, retrospective cohort analysis comparing 321 CLL patients treated with VENmono vs VENcombo across the United States and the United Kingdom. We examined demographics, baseline characteristics, dosing, adverse events, response rates, and outcomes. The primary endpoints were progression-free survival (PFS) and overall survival (OS), estimated by Kaplan-Meier method, in patients treated with VENmono vs VENcombo. Univariate and bivariate analyses were performed with COX regression. Three hundred twenty-one CLL patients were included (3 median prior treatments, 78% prior ibrutinib). The overall response rates (ORRs) were similar (VENmono, 81% ORR, 34% complete remission [CR] vs VENcombo, 84% ORR, 32% CR). With a median follow-up of 13.4 months, no differences in PFS and OS were observed between the groups. In unadjusted analyses, the hazard ratios (HRs) for PFS and OS for VENmono vs VENcombo were HR 1.0 (95% confidence interval [CI], 0.6-1.8; P = .7) and HR 1.2 (95% CI, 0.6-2.3; P = .5), respectively. When adjusting for differences between the cohorts, the addition of an anti-CD20 antibody in combination with VEN did not impact PFS (HR, 1.0; 95% CI, 0.5-2.0; P = .9) or OS (HR, 1.1; 95% CI, 0.4-2.6; P = .8). We demonstrate comparable efficacy between VENmono and VENcombo in a heavily pretreated, high-risk, retrospective cohort, in terms of both response data and survival outcomes. Prospective studies are needed to validate these findings.

Tumor Lysis, Adverse Events, and Dose Adjustments in 297 Venetoclax-Treated CLL Patients in Routine Clinical Practice.

PURPOSE: Clinical trials of venetoclax reported negligible rates of clinical tumor lysis syndrome (TLS) in patients with chronic lymphocytic leukemia (CLL) when using an extended dose escalation schedule. We aimed to understand TLS prophylaxis, rates of select adverse events (AE), and impact of dosing modifications in routine clinical practice. EXPERIMENTAL DESIGN: This retrospective cohort study included 297 CLL venetoclax-treated patients outside of clinical trials in academic and community centers. Demographics, baseline disease characteristics, venetoclax dosing, TLS risk and prophylaxis, and AEs were collected. RESULTS: The group was 69% male, 96% had relapsed/refractory CLL, 45% had deletion chromosome 17p, 84% had unmutated IGHV, 80% received venetoclax monotherapy, and median age was 67. TLS risk was categorized as low (40%), intermediate (32%), or high (28%), and 62% had imaging prior to venetoclax initiation. Clinical TLS occurred in 2.7% of patients and laboratory TLS occurred in 5.7%. Pre-venetoclax TLS risk group and creatinine clearance independently predict TLS development in multivariable analysis. Grade 3/4 AEs included neutropenia (39.6%), thrombocytopenia (29.2%), infection (25%), neutropenic fever (7.9%), and diarrhea (6.9%). Twenty-two patients (7.4%) discontinued venetoclax due to an AE. Progression-free survival was similar regardless of number of dose interruptions, length of dose interruption, and stable venetoclax dose. CONCLUSIONS: These data provide insights into current use of venetoclax in clinical practice, including TLS rates observed in clinical practice. We identified opportunities for improved adherence to TLS risk stratification and prophylaxis, which may improve safety.

Breast cancer patients with brain metastasis undergoing GKRS.

BACKGROUND: Breast cancer (BC) is the second most common cause of brain metastasis in the United States. Compared to whole brain radiation therapy (WBRT), treatment with gamma-knife radiosurgery (GKRS) offers a better chance at neurocognitive preservation. The goal of our retrospective study is to report the overall survival (OS) in patients receiving GKRS and to identify factors that improve survival outcomes. METHODS: The records of 80 patients with primary BC treated with GKRS at the Yale Comprehensive Cancer Center between 2000 and 2013 were reviewed. OS was calculated from the date of first GKRS treatment. Other factors studied were age, Karnofsky performance status (KPS), tumor subtype, having WBRT and/or surgical resection pre- or post-GKRS, and number of brain metastases treated with GKRS. RESULTS: Median age was 56.2 years. OS from first GKRS was 13.1 months (95% CI 7.6-21.9). On univariate analysis, improved survival was associated with HER-2 subtype (p = 0.026), KPS score > 80 (p = 0.009), and good control of systemic disease at time of GKRS (p = 0.020). Multivariable analysis detected a significantly longer survival with HER-2 positivity (HR 0.22, 95% CI 0.06-0.76, p = 0.017) and a strong trend in patients with craniotomy prior to GKRS (HR 0.13, 95% CI 0.01-1.11, p = 0.06). CONCLUSIONS: GKRS is a promising therapy for treating brain metastasis from BC, particularly in those with HER-2 positivity and high-performance scores even in those patients with > 5 brain metastases. Furthermore, GKRS may also be a useful adjunct to surgical resection in such patients. High rates of neurological death remain from BC brain metastases; however, and need further investigation.

Chemotherapy for Elderly Ovarian Cancer Patients.

OBJECTIVE: Ovarian cancer is the most lethal cancer involving the female pelvic reproductive system. Its incidence increases with age and with an aging population, its prevalence should also increase. The goal of our retrospective study is to report our experience in treating women over 65 years of age, with a diagnosis of primary ovarian cancer, using standard intravenous chemotherapy. METHODS: The medical records of 78 patients>65 years of age diagnosed with primary ovarian cancer at the Yale Cancer Center between 1996-2006 were retrospectively reviewed and included in our analysis. Patients had stage I-IV disease (stage I n=5, stage II n=8, stage III n=36, stage IV n=25, unknown n=4). RESULTS: Sixty-three of 78 women (80.8%) completed the prescribed regimen; and 62 women did not require a dose reduction or chemotherapy discontinuation. The most common reason for a dose reduction or treatment discontinuation was fatigue (6.4%), neutropenia (2.6%), patient preference (2.6%), and multiple co-morbidities (2.6%). The most commonly used regimen was paclitaxel 175mg/m2 and carboplatin AUC 5. The hazard ratio for PFS and OS for patients who had dose reduction/discontinuation versus those who completed the prescribed dose was 1.3 (95% CI 0.51-3.26) and 0.63 (95% CI 0.17-2.33), respectively. CONCLUSIONS: Our findings illustrate that elderly women are able to tolerate standard chemotherapy with relatively few significant adverse effects. While different treatment modalities in ovarian cancer are continually being evaluated, additional prospective studies are required to better understand the tolerability and efficacy of such treatment in the elderly population.