Rahul Ladwa

The cessation of anti-PD-1 antibodies of complete responders in metastatic melanoma

The optimal duration of PD-1 antibodies for metastatic melanoma is unknown. In previous trials, there has been the potential to cease therapy if the patient achieves a complete response (CR). We aimed to assess the outcomes of patients who had ceased anti-PD-1 antibodies in this setting. A retrospective review was carried out of CR to PD-1-based therapy across two institutions. Patients were from the Pembrolizumab Named Patient Program (PEM NPP), Nivolumab monotherapy (NIVO), and reimbursed Pembrolizumab (r PEM). Patients had to have experienced a CR to PD-1-based therapy and ceased therapy because of this. Disease recurrence was the primary outcome measured. Twenty-nine patients (PEM NPP, N=20; Nivo, N=3; r PEM, N=6) ceased anti-PD-1 therapy after CR for observation. The median age was 64 (27–83) years. All patients had treatment discontinued for observation. The median time to CR was 10.5 months in the PEM NPP, 7.5 months on r PEM groups, and 17 months in the NIVO group. The median time off therapy in PEM NPP was 10 months, NIVO was 9 months, and r PEM was 4.5 months. To date, three patients have shown a relapse at a median follow-up off treatment of 8 months. This is the first report of patients who have intentionally ceased PD-1-based therapy because of CR. With a follow-up of 8 months off treatment, the risk of relapse was low. Data such as these are clinically relevant as we need to be able to discuss cessation of therapy and relevant from a pharmacoeconomic perspective, given the cost of PD-1 antibodies to society.

Posterior Reversible Encephalopathy Syndrome in Early-Stage Breast Cancer.

Wider use of chemotherapy and targeted agents can be associated with posterior reversible encephalopathy syndrome (PRES). This syndrome is most commonly found in metastatic adenocarcinoma treated with platinum‐based analogs and is managed with cessation of the precipitating medication. We present the first case of PRES in early‐stage breast cancer and discuss the further management of this condition. Recognition of this condition and correction of identifiable precipitating factor including cessation of relevant medications remains important in its management.

Maintaining Dose Intensity of Adjuvant Chemotherapy in Older Patients With Breast Cancer

Introduction Maintaining the relative dose intensity (RDI) of adjuvant chemotherapy at ≥ 85% has been associated with improved treatment outcomes in early‐stage breast cancer (ESBC). Increasing evidence has suggested that patients aged ≥ 65 years can maintain the optimal RDI for standard chemotherapy regimens. The present study investigated the RDI of newer adjuvant chemotherapy regimens in this demographic. Patients and Methods We retrospectively analyzed the data from 281 patients aged ≥ 65 years with a diagnosis of ESBC who had received adjuvant chemotherapy across 3 sites in Queensland, Australia from 2010 to 2015. The primary endpoint was the proportion of patients who had received an RDI of ≥ 85%. Results The median age at diagnosis was 68 years (range, 65‐85 years), with 36.3% aged > 70 years. The patient characteristics included tumor stage T3 or T4 in 17% and node‐positive disease in 60%. The common chemotherapy regimens included docetaxel/cyclophosphamide (23%), 5‐fluorouracil/epirubicin/cyclophosphamide plus docetaxel or paclitaxel (17%); Adriamycin/cyclophosphamide/weekly paclitaxel (38%); and docetaxel/carboplatin/trastuzumab (11%). Primary (15%) and secondary (54%) granulocyte colony‐stimulating factor (G‐CSF) was used. An RDI of ≥ 85% was achieved in 63% of the patients. Significant associations were noted between a reduced RDI and age ≥ 70 years (P < .001), Charlson comorbidity index ≥ 1 (P = .043), initial dose reductions (P = .01), secondary G‐CSF use (P = .45), hospital admission (P < .001), and febrile neutropenia (P = .007). Treatment‐related toxicities were the most common reason for noncompletion, with high rates of hospital admissions (46%) and febrile neutropenia (22%). Conclusion Our findings suggest that patients aged ≥ 65 years with ESBC can maintain an optimal RDI with modern chemotherapy regimens. Appropriate geriatric assessment and the use of supportive measures such as G‐CSF could better assist select groups to maintain an optimal dose intensity. Micro‐Abstract A suboptimal dose intensity of adjuvant chemotherapy has been associated with a poor prognosis in patients with early‐stage breast cancer. We investigated the relative dose intensity (RDI) of modern adjuvant chemotherapy regimens in patients aged ≥ 65 years. An RDI of ≥ 85% was achieved in 177 of 281 included patients (63%). Better supportive care of risk groups might further optimize the RDI.

The changing paradigm of management in melanoma brain metastases

Improved systemic treatment has improved the prognosis of metastatic melanoma (MM). However, brain metastases (BMs) are a frequent complication. We aimed to explore the outcome of these patients with modern therapeutic options.

A rare case of omentum invasive prostate cancer: Staging with PSMA PET/CT imaging and response to systemic therapy

The omentum is a rare metastatic site for prostatic adenocarcinoma. We present a case of metastatic castrate-resistant prostate cancer, with progressive omentum invasive prostate cancer identified on prostate-specific membrane antigen (PSMA) PET/CT scan. Omental biopsy revealed metastatic prostate adenocarcinoma, and cabazitaxel chemotherapy was instituted with a prostate-specific antigen biochemical response. Repeat PSMA PET/CT imaging revealed increased avidity in omental metastasis. Despite prostate-specific antigen response, PSMA PET/CT did not correlate with a therapeutic response.

The Feasibility and Tolerability of Newer Chemotherapy Regimens in the Adjuvant Setting in Older Patients with Breast Cancer.

To the Editor: Breast cancer remains the commonest cause of cancer for females in Australia and worldwide. Median age at presentation in Australia is 61 years of age. One in four patients are aged over 70 years (1). With a growing elderly population and newer chemotherapy options available for the adjuvant treatment of breast cancer, little is known of the tolerability and feasibility. Historically, older patients were thought to tolerate chemotherapy poorly and doses were subsequently lowered affecting dose intensity (2). Relatively few patients over 65 years old are enrolled in adjuvant trials (3). Maintaining dose intensity has been shown to improve overall survival and disease-free survival (4– 6). Several retrospective studies have suggested dose intensity is maintained in patients over 65 years of age with first and second generation chemotherapy regimens (7–10). We retrospectively analyzed 67 females aged 65 years or older at our institution to assess tolerability and safety of newer adjuvant chemotherapy for early stage breast cancer. The primary endpoint of the study was to assess the proportion of patients reaching a dose intensity of over 85% using the Hryniuk method (11,12). Median age was 68 years old ranging from 65 to 85 years. The most common age group ranged from 65 to 69 (66%). Patients were considered overweight or obese in 68% of cases. Baseline ECOG status was 0 in 94%. Most commonly present tumor characteristics included IDC (90%), T-stage 1 or 2 (89%) and tumor grade 2 or 3 (96%). Node positivity was present in 51% of cases. Hormone receptor positivity was present in 69% of patients, whereas HER2 positivity was present in 27%. Patients had at least 1 or more comorbidities, as measured by the Charlson index, in 28% (13). Mastectomy was performed in 78% of cases. Adjuvant radiotherapy was performed in 40%. Commonly used chemotherapy regimens included 5-fluorouracil/epirubicin/cyclophosphamide – docetaxel (FEC-D) in 34%, docetaxel/cyclophosphamide (TC) in 21%, adriamycin/cyclophosphamide paclitaxel (AC-T) in 19% and docetaxel/carboplatin/ Herceptin (TCH) in 16%. Tolerability and feasibility data are summarized in Table 1. All cycles of planned chemotherapy were completed in 60% of cases and dose intensity over 85% was met in 49% of patients. Most common reason for treatment discontinuation was chemotherapy toxicity (86%) including peripheral neuropathy, diarrhea, nausea, vomiting, fatigue, and febrile neutropenia. Patients aged 65–69 were more likely to maintain a higher relative dose intensity (RDI) compared to patients aged 70 years or over (Mean RDI 83 versus 66; p = 0.028). Other predictors of a higher RDI include absence of comorbidities (Mean RDI; absence 81 versus presence 66, p = 0.07) and absence of admissions (mean RDI; absence 84 versus presence 70.5, p = 0.033). These results differ from four other retrospective analyses performed with few newer chemotherapy agents (Table 2). In 2013, Lyman et al. studied 103 patients of which 61 were treated with TC chemotherapy (7). A RDI <85 was recorded in 19%. Furthermore in 2012, Oladipo et al. studied 101 patients of which the common treatment regimens included FEC 100 (N = 15) and AC (N = 14). A RDI <85% was seen in 22% (8). Age distributions of a subset of these patients are similar to our patient population, but our study used more third generation chemotherapy. Notable differences between our results and other studies include the use of primary GCSF prophylaxis. Lyman et al. 2013 use Address correspondence and reprint requests to: Rahul Ladwa, Cancer Care Services, Gold Coast University Hospital, Southport, QLD 4215, Australia, or e-mail: rl57@hotmail.co.uk

A single center experience of cardiac metastasis from neuroendocrine tumors (net)

COSAs 43 and ANZBCTGs 38 Annual Scientific Meetings. Partners for Progress in Breast Cancer Research and Care. 15–17 November