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Objective: To evaluate the efficacy of sequential treatment with ipilimumab and nivolumab following progression on nivolumab monotherapy in individuals with advanced, non‐clear‐cell renal cell carcinoma (nccRCC). Materials and Methods: UNISoN (ANZUP1602; NCT03177239) was an open‐label, single‐arm, phase 2 clinical trial that recruited adults with immunotherapy‐naïve, advanced nccRCC. Participants received nivolumab 240 mg i.v. two‐weekly for up to 12 months (Part 1), followed by sequential addition of ipilimumab 1 mg/kg three‐weekly for four doses to nivolumab if disease progression occurred during treatment (Part 2). The primary endpoint was objective tumour response rate (OTRR) and secondary endpoints included duration of response (DOR), progression‐free (PFS) and overall survival (OS), and toxicity (treatment‐related adverse events). Results: A total of 83 participants were eligible for Part 1, including people with papillary (37/83, 45%), chromophobe (15/83, 18%) and other nccRCC subtypes (31/83, 37%); 41 participants enrolled in Part 2. The median (range) follow‐up was 22 (16–30) months. In Part 1, the OTRR was 16.9% (95% confidence interval [CI] 9.5–26.7), the median DOR was 20.7 months (95% CI 3.7‐not reached) and the median PFS was 4.0 months (95% CI 3.6–7.4). Treatment‐related adverse events were reported in 71% of participants; 19% were grade 3 or 4. For participants who enrolled in Part 2, the OTRR was 10%; the median DOR was 13.5 months (95% CI 4.8–19.7) and the median PFS 2.6 months (95% CI 2.2–3.8). Treatment‐related adverse events occurred in 80% of these participants; 49% had grade 3, 4 or 5. The median OS was 24 months (95% CI 16–28) from time of enrolment in Part 1. Conclusions: Nivolumab monotherapy had a modest effect overall, with a few participants experiencing a long DOR. Sequential combination immunotherapy by addition of ipilimumab in the context of disease progression to nivolumab in nccRCC is not supported by this study, with only a minority of participants benefiting from this strategy. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen positron emission tomography-computed tomography use prior to systemic therapy in metastatic castration-resistant prostate cancer Abbreviations (m)CRPC (metastatic) castration-resistant prostate cancer ePAD electronic Prostate Cancer Australian Database FDG fluorodeoxyglucose HSPC hormone-sensitive prostate cancer LN lymph nodes PET positron emission tomography PSMA prostate-specific membrane antigen WBBS whole-body bone scan Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-CT imaging has demonstrated greater sensitivity compared to conventional imaging modalities with CT and whole-body bone scan (WBBS) in the detection of metastatic prostate cancer [[1]]. A further 15 patients (17%) had dedicated CT alone in addition to PSMA PET-CT, while eight (9%) had additional WBBS alone in addition to PSMA PET-CT (Fig. [Extracted from the article]

Aims: Multiple life‐prolonging therapies are available for metastatic castration‐resistant prostate cancer (mCRPC). However, the optimal treatment strategy following progression through standard treatment with docetaxel, androgen receptor signaling inhibitor (ARSI) and cabazitaxel, remains unclear. We aimed to describe treatment patterns in men with mCRPC following progression on standard treatments and determine whether subsequent treatment choice impacts overall survival. Methods: Clinicopathologic and treatment data were extracted from the electronic CRPC Australian Database (ePAD) for patients who had received docetaxel, ARSIs and cabazitaxel in any order. Data were analyzed to compare groups that did versus did not receive subsequent systemic therapy. Treatment sequences, median duration of treatment, and median overall survival (mOS) were reported for each treatment group. Results: Ninety‐eight eligible patients were identified, with 51 receiving subsequent systemic therapy. Those who received further treatment were younger (68 vs. 71 years, p <.01) but did not have any other differences in clinicopathologic features compared to those who received no further treatment. Patients who received upfront docetaxel were more likely to proceed to subsequent treatment (p =.02). Subsequent systemic therapies varied, the most common being carboplatin‐based regimens (n = 13, 25.5%) and many patients were rechallenged with ARSI (n = 10, 19.6%) or docetaxel (n = 6, 11.8%). There was no difference in mOS according to subsequent systemic therapy (p =.09). Conclusion: This retrospective multicenter analysis demonstrates the variation in treatment sequences used for mCRPC in the real‐world setting. In the absence of high quality, prospective evidence, our results suggest that subsequent treatment choice does not influence survival outcomes and the optimal choice is guided by individual patient and disease‐related factors. [ABSTRACT FROM AUTHOR]

Objective: To report treatment patterns and survival outcomes of patients with relapsed and refractory metastatic germ cell tumours (GCTs) treated with high‐dose chemotherapy (HDCT) and autologous stem‐cell transplantation in low‐volume specialized centres within the widely dispersed populations of Australia and New Zealand between 1999 and 2019. Patients and Methods: We conducted a retrospective analysis of 111 patients across 13 institutions. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. We reviewed treatment regimens, survival outcomes, deliverability and toxicities. Primary endpoints included overall (OS) and progression‐free survival (PFS). Cox proportional hazards models were used to test the association of survival outcomes with patient and treatment factors. Results: The median (range) age was 30 (14–68) years and GCT histology was non‐seminomatous in 84% of patients. International Prognostic Factors Study Group (IPFSG) prognostic risk category was very low/low, intermediate, high and very high in 18%, 36%, 25% and 21% of patients, respectively. Salvage conventional‐dose chemotherapy (CDCT) was administered prior to HDCT in 59% of patients. Regimens included paclitaxel, ifosfamide, carboplatin and etoposide (50%), carboplatin and etoposide (CE; 28%), carboplatin, etoposide and ifosfamide (CEI; 6%), carboplatin, etoposide and cyclophosphamide (CEC; 5%), CEC‐paclitaxel (6%) and other (5%). With a median follow‐up of 4.4 years, the 1‐, 2‐ and 5‐year PFS rates were 62%, 57% and 52%, respectively, and OS rates were 73%, 65% and 61%, respectively. There were five treatment‐related deaths. Progression on treatment occurred in 17%. In a univariable analysis, worse International Germ Cell Cancer Collaborative Group (IGCCCG) and IPFSG prognostic groups were associated with inferior survival outcomes. An association of inferior survival was not found with the number of high‐dose cycles received nor when HDCT was delivered after salvage CDCT. Conclusion: This large dual‐national registry‐based study reinforces the efficacy and deliverability of HDCT for relapsed and refractory metastatic GCT in low‐volume specialized centres in Australia and New Zealand, with survival outcomes comparable to those found in international practice. [ABSTRACT FROM AUTHOR]

Aim: There is scarcity of research for the nutritional management of pelvic radiotherapy in gynaecological malignancies and delivery of specialised nutrition care is limited due to the current knowledge gap in guidelines. This study aimed to better understand the nutritional risk, weight changes and pattern of nutrition impact symptoms occurring at various treatment timepoints in this population, to inform an effective model of care. Methods: This retrospective, observational study included women with gynaecological cancers receiving pelvic radiotherapy at a tertiary hospital from January 2017 to December 2018 (n = 104). Information was collected on: first day of radiotherapy; weekly during treatment; acute‐phase post‐treatment (0–6 weeks); and intermediate‐phase post‐treatment (6 weeks to 6 months). This study reported on incidence of clinically significant weight change (±5%), documented nutrition impact symptoms and the current nutrition care model (nutrition screening, referral, assessment and interventions). Results: Clinically significant weight loss was experienced by 38% (n = 40/104) of patients prior to commencing treatment and 19% (n = 14/73) during treatment. Diarrhoea (n = 40/79), fatigue (n = 54/79), nausea (n = 38/79) and pain (n = 31/79) were frequently reported during treatment, and fatigue (n = 33/92) and pain (n = 25/92) continued acutely post‐treatment. Despite high rates of weight loss and prevalence of nutrition impact symptoms, only 38% (n = 40/104) of patients were referred to a dietitian. Conclusions: A considerable proportion of patients with gynaecological cancers are at nutrition risk before and during treatment due to clinically significant weight loss and prevalence of nutrition impact symptoms experienced. This highlights the importance of nutrition‐risk screening and access to specialised dietetic care as part of their model of care. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of rucaparib maintenance treatment in ARIEL3 were evaluated in subgroups based on best response to most recent platinum‐based chemotherapy and baseline disease. Methods: Patients were randomized 2:1 to receive either oral rucaparib at a dosage of 600 mg twice daily or placebo. Investigator‐assessed PFS was assessed in prespecified, nested cohorts: BRCA‐mutated, homologous recombination deficient (HRD; BRCA mutated or wild‐type BRCA/high loss of heterozygosity), and the intent‐to‐treat (ITT) population. Results: Median PFS for patients in the ITT population with a complete response to most recent platinum‐based chemotherapy was 11.1 months in the rucaparib arm (126 patients) versus 5.6 months in the placebo arm (64 patients) (HR, 0.33 [95% CI, 0.23–0.48]), and in patients with a partial response (249 vs. 125), it was 9.0 versus 5.3 months (HR, 0.38 [0.30–0.49]). In subgroups of the ITT population based on baseline disease, median PFS was 8.2 versus 5.3 months (HR, 0.40 [0.28–0.57]) in patients with measurable disease (141 rucaparib vs. 66 placebo), 10.4 versus 4.5 months (HR, 0.31 [0.20–0.48]) in those with nonmeasurable but evaluable disease (104 vs. 56), and 14.1 versus 7.3 months (HR, 0.35 [0.24–0.51]) in those with no residual disease (130 vs. 67). Across subgroups, significantly longer median PFS was observed with rucaparib versus placebo in the BRCA‐mutated and HRD cohorts. Objective responses were reported in patients with measurable disease and in patients with nonmeasurable but evaluable baseline disease. Safety was consistent across subgroups. Conclusion: Rucaparib maintenance treatment provided clinically meaningful efficacy benefits across subgroups based on response to last platinum‐based chemotherapy or baseline disease. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the recent real‐world use of first‐generation antiandrogens (FGAs) in metastatic castration‐resistant prostate cancer (mCRPC) using a retrospective multicentre cohort study. Patients and Methods: The electronic CRPC Australian Database (ePAD) was interrogated to identify patients with mCRPC. Clinicopathological features, treatment and outcome data, stratified by FGA use, were retrieved and reported through descriptive statistics. Survival analyses were calculated using the Kaplan–Meier method and groups compared using log‐rank tests. Factors influencing overall survival (OS) were analysed using Cox proportional hazards regression model. Results: We identified 634 patients with mCRPC, enrolled in ePAD between January 2016 and March 2019, including 322 (51%) who received FGAs. The median follow‐up was 21.9 months. Patients treated with FGAs were more likely to have lower International Society of Urological Pathologists (ISUP) grade group (P = 0.04), longer median time to CRPC (25.6 vs 16.0 months, P < 0.001), and were less likely to have visceral metastases (5.0% vs 11.2%, P = 0.005) or to have received upfront docetaxel (P < 0.001). A ≥50% reduction from pre‐treatment prostate‐specific antigen (PSA) level (PSA50 response) during FGA treatment occurred in 119 (37%) patients and was independently associated with improved OS (hazard ratio 0.233, P < 0.001). Prior FGA treatment did not significantly influence the selection of subsequent life‐prolonging treatments for mCRPC or their PSA50 response rates. Conclusion: In our present cohort, FGAs were commonly used in lower‐risk mCRPC and their use did not significantly influence the choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy was an independent favourable prognostic marker associated with improved OS. [ABSTRACT FROM AUTHOR]

Aim: Optimal treatment for newly diagnosed metastatic hormone‐sensitive prostate cancer (mHSPC) has evolved, with many patients deriving benefit from the addition of docetaxel to androgen deprivation therapy (D‐ADT). This study sought to define the therapy used and associated activity following D‐ADT. Methods: Retrospective analysis of patients with mHSPC treated with one or more cycles of D‐ADT who were identified from a prospectively maintained multisite prostate cancer database of patients treated in a community or academic center setting in Australia. The primary endpoint of this study was first‐line time to treatment failure (1L TTF) for subsequent treatment of metastatic Castrate Resistant Prostate Cancer (mCRPC), with secondary endpoints of prostate‐specific antigen (PSA) reduction >50% and time from 1L to second‐line (2L) treatment initiation. Results: A total of 93 patients received D‐ADT for mHSPC, 85 (91%) had subsequent treatment for mCRPC. Median time to mCRPC (biochemical, clinical or radiographic) had been 14.8 months (95% confidence interval [CI], 11.9–16.5). 1L treatment was enzalutamide 47 patients (55%), abiraterone 23 (27%), cabazitaxel 7 (8%), docetaxel 4 (5%) and other therapies 4 (5%). Median 1L TTF was 6.3 months (95% CI, 4.9–7.6), PSA > 50% reduction was achieved in 32 of 89 patients (36%), median time from 1L to second‐line treatment was 7.3 months (1.3–27.4), which did not differ significantly between treatment groups. Conclusions: Abiraterone, enzalutamide, cabazitaxel and docetaxel all demonstrate activity following progression on D‐ADT. No difference in efficacy was detected between treatment options for mCRPC. Prospective trials investigating the optimal treatment sequence for prostate cancer following progression on D‐ADT needed. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor receptor tyrosine kinase inhibitors have provided an effective standard of care for the treatment of metastatic clear cell renal cell carcinoma (mRCC). Survival is prolonged with emergence of modern immuno‐oncology combination regimens. Prognostic risk assessment is essential for choosing between these therapies to determine the most appropriate first line treatment option, with selection based on International Metastatic RCC Database Consortium Risk Category. We review the current subsidized first line treatments for mRCC in Australia and consider the evidence for treatment selection and sequencing. [ABSTRACT FROM AUTHOR]

Purpose: Olaparib was originally formulated as 50 mg capsules with a recommended dose of 400 mg twice daily which requires patients to take 16 capsules a day. More recently, a tablet formulation with equivalent efficacy has become available and reduces the pill burden for patients to two tablets twice daily which is more convenient for patients. However, it is important to understand the key differences between the olaparib capsule and tablet formulations as they are not bioequivalent, and the doses are not interchangeable. Educating patients when transitioning from capsules to tablets is critical to avoid dosing errors and maintain both safety and efficacy of olaparib maintenance therapy. Main recommendations: There are no established guidelines on transitioning patients from capsules to tablets. Patients taking 400 mg of the capsules twice daily should be switched to 300 mg of the tablets twice daily. In patients on a reduced dose of 200 mg capsules twice daily, consider switching to 250 mg twice daily of the tablet formulation. In patients on 100 mg capsules twice daily, consider 200 mg tablets twice daily. Particular care should be taken in transitioning patients who are on a reduced dose due to anemia and who have a low hemoglobin (9 g/dL) where a lower dose of the tablets should be considered initially. Close monitoring of patients for the first 3 months with further dose reductions based on tolerability is recommended. The tablet dose can be escalated or de‐escalated depending on tolerance. [ABSTRACT FROM AUTHOR]

Denosumab, a bone-modifying agent, reduces the risk of skeletal-related events in patients with bone metastases from solid tumors and is generally well tolerated. However, hypocalcemia, osteonecrosis of the jaw (ONJ) and atypical fracture are potential and important toxicities of denosumab therapy that require attention. In pivotal phase III trials in patients with bone metastases from solid tumors, the incidence of hypocalcemia was 9.6% in denosumab-treated patients, with most events being asymptomatic, grade 2 and resolving by week 4. Established hypocalcaemia requires additional short-term calcium and vitamin D supplementation and, if severe, administration of intravenous calcium. ONJ was reported in 1.8% of patients receiving denosumab over 3 years in these trials. Involvement of an experienced oro-maxillary surgeon is important if ONJ is suspected. Atypical fractures were rare in a large study of denosumab using the dose and scheduling approved for the treatment of osteoporosis. To prevent toxicities, patients should maintain calcium and vitamin D supplementation, good oral hygiene and regular dental reviews throughout treatment. This article presents case studies from our clinical practice and discusses the pathophysiology of these toxicities along with guidance on prevention, diagnosis and management. [ABSTRACT FROM AUTHOR]

Olaparib is the first oral poly(ADP-ribose) polymerase inhibitor to be approved as maintenance monotherapy for treatment of patients with platinum-sensitive relapsed BRCA-mutated ( BRCAm) serous ovarian cancer. This review provides practical guidance on the use of olaparib (capsule formulation) in the maintenance setting. The article focuses on the key toxicities that can arise with olaparib therapy and recommendations for their management. Nausea, vomiting, fatigue and anemia are the most commonly reported adverse events in olaparib clinical trials and are generally mild to moderate and transient in nature in most patients. Implementation of an effective and timely management plan can control many of the side effects. It is vital that health care providers effectively communicate the potential side effects of olaparib, as well as educate patients on management strategies to combat these symptoms. To this end, realistic expectations regarding the potential side effects need to be set, with an understanding that dose interruptions and modifications may be required to allow patients to continue receiving treatment. [ABSTRACT FROM AUTHOR]

This is a contemporaneous review of the frontline treatment of epithelial ovarian cancer (EOC), specifically on the importance of optimal surgical cytoreductive surgery, the pivotal role of platinum-based adjuvant chemotherapy (which encompasses intraperitoneal and dose-dense regimens) and the emergence of neo-adjuvant chemotherapy. Additionally, the benefit of concurrent and maintenance bevacizumab in the suboptimally debullked stage III and stage IV EOC setting is also reviewed. The article also discusses the increasing importance of prognostic and predictive molecular biomarkers in the future management of EOC. [ABSTRACT FROM AUTHOR]