Ribociclib may potentiate rosuvastatin effect in causing late onset rhabdomyolysis.

A woman in her 50s with metastatic hormone receptor positive breast cancer developed rhabdomyolysis and subsequent acute kidney injury while on a combination of ribociclib and rosuvastatin therapy. She had been taking both medications long term and had recently recommenced her ribociclib at her usual dose after a routine 1 week break. Cyclin-dependent kinase 4/6 inhibitors have been implicated in causing rhabdomyolysis by potentiating statin effect by way of inhibition of cytochrome P450 enzymatic action and decreasing hepatic membrane transporter function. This is the first case in which the combination of ribociclib and rosuvastatin has been shown to cause this adverse effect. It is also one of the first to demonstrate this effect occurring years after commencement of therapy. Continued vigilance for this side effect should be maintained long term.

Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

BACKGROUND: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood. METHODS: We conducted a trial to assess whether a ctDNA-guided approach could reduce the use of adjuvant chemotherapy without compromising recurrence risk. Patients with stage II colon cancer were randomly assigned in a 2:1 ratio to have treatment decisions guided by either ctDNA results or standard clinicopathological features. For ctDNA-guided management, a ctDNA-positive result at 4 or 7 weeks after surgery prompted oxaliplatin-based or fluoropyrimidine chemotherapy. Patients who were ctDNA-negative were not treated. The primary efficacy end point was recurrence-free survival at 2 years. A key secondary end point was adjuvant chemotherapy use. RESULTS: Of the 455 patients who underwent randomization, 302 were assigned to ctDNA-guided management and 153 to standard management. The median follow-up was 37 months. A lower percentage of patients in the ctDNA-guided group than in the standard-management group received adjuvant chemotherapy (15% vs. 28%; relative risk, 1.82; 95% confidence interval [CI], 1.25 to 2.65). In the evaluation of 2-year recurrence-free survival, ctDNA-guided management was noninferior to standard management (93.5% and 92.4%, respectively; absolute difference, 1.1 percentage points; 95% CI, -4.1 to 6.2 [noninferiority margin, -8.5 percentage points]). Three-year recurrence-free survival was 86.4% among ctDNA-positive patients who received adjuvant chemotherapy and 92.5% among ctDNA-negative patients who did not. CONCLUSIONS: A ctDNA-guided approach to the treatment of stage II colon cancer reduced adjuvant chemotherapy use without compromising recurrence-free survival. (Supported by the Australian National Health and Medical Research Council and others; DYNAMIC Australian New Zealand Clinical Trials Registry number, ACTRN12615000381583.).

RESILIENT part 1: a phase 2 dose-exploration and dose-expansion study of second-line liposomal irinotecan in adults with small cell lung cancer.

BACKGROUND: RESILIENT (NCT03088813) is a phase 2/3 study assessing the safety, tolerability, and efficacy of liposomal irinotecan monotherapy in patients with small cell lung cancer and disease progression on/after first-line platinum-based therapy. Here, we present results from RESILIENT part 1. METHODS: This open-label, single-arm, safety run-in evaluation with dose-exploration and dose-expansion phases included patients ≥18 years old with Eastern Cooperative Oncology Group performance status of 0/1; those with asymptomatic central nervous system metastases were eligible. The primary objectives were to evaluate safety and tolerability and recommend a dose for further development. Efficacy end points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: During dose exploration, 5 patients received intravenous liposomal irinotecan at 85 mg/m2 (deemed not tolerable; dose-limiting toxicity) and 12 patients received 70 mg/m2 (deemed tolerable). During dose expansion, 13 additional patients received intravenous liposomal irinotecan at 70 mg/m2 . Of these 25 patients (median age [range], 59.0 [48.0-73.0] years, 92.0% with metastatic disease), 10 experienced grade ≥3 treatment-related treatment-emergent adverse events (TEAEs), most commonly diarrhea (20.0%) and neutropenia (16.0%), and 3 had serious treatment-related TEAEs, of whom 2 died. ORR was 44.0% (95% confidence interval [CI]: 24.40-65.07; 1 complete response, 10 partial responses) and median (95% CI) PFS and OS were 3.98 (1.45-4.24) months and 8.08 (5.16-9.82) months, respectively. CONCLUSION: Overall, no new safety signals were identified with liposomal irinotecan, and antitumor activity was promising. RESILIENT part 2, a randomized, controlled, phase 3 study of liposomal irinotecan versus topotecan, is ongoing. LAY SUMMARY: Small cell lung cancer (SCLC) is an aggressive disease with few treatment options after platinum-based therapy. Administering 1 option, irinotecan, as a "liposomal" formulation, may extend drug exposure and improve outcomes. The RESILIENT part 1 trial assessed the safety and efficacy of liposomal irinotecan in 25 adults with SCLC after disease progression despite platinum-based therapy. No new safety concerns were reported. The most common moderate-to-severe side effects were diarrhea (20% of patients) and neutropenia (16%). Tumors responded to treatment in 44% of patients. Average survival was 8.08 months, and time to disease progression was 3.98 months. Liposomal irinotecan trials are ongoing.

The association between quality care and outcomes for a real-world population of Australian patients diagnosed with pancreatic cancer.

BACKGROUND: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival. METHODS: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. RESULTS: 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96). CONCLUSION: Capture of a concise data set has enabled quality of care to be assessed.

Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer.

Detection of circulating tumor DNA (ctDNA) after resection of stage II colon cancer may identify patients at the highest risk of recurrence and help inform adjuvant treatment decisions. We used massively parallel sequencing-based assays to evaluate the ability of ctDNA to detect minimal residual disease in 1046 plasma samples from a prospective cohort of 230 patients with resected stage II colon cancer. In patients not treated with adjuvant chemotherapy, ctDNA was detected postoperatively in 14 of 178 (7.9%) patients, 11 (79%) of whom had recurred at a median follow-up of 27 months; recurrence occurred in only 16 (9.8 %) of 164 patients with negative ctDNA [hazard ratio (HR), 18; 95% confidence interval (CI), 7.9 to 40; P < 0.001]. In patients treated with chemotherapy, the presence of ctDNA after completion of chemotherapy was also associated with an inferior recurrence-free survival (HR, 11; 95% CI, 1.8 to 68; P = 0.001). ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence.

A Discrete Choice Experiment to Examine the Preferences of Patients With Cancer and Their Willingness to Pay for Different Types of Health Care Appointments.

BACKGROUND: This study sought to understand the preferences of patients with cancer and the trade-offs between appointment attributes using discrete choice experiment (DCE). METHODS AND STUDY DESIGN: Patients with cancer at 3 hospitals completed a self-administered DCE. Each scenario described 6 attributes: expertise of health care professionals (HCPs), familiarity of doctors with patients' medical history, waiting time, accompaniment by family/friends, travel time, and out-of-pocket costs. Patient preferences were estimated using logistic regression. Willingness to pay (WTP) estimates were derived from regression coefficients. RESULTS: Of 512 patients contacted, 185 returned the questionnaire. The mean age was 61 years, and 60% of respondents were female. The mean time since cancer diagnosis was 34 months, 90% had received treatment; and 61% had early-stage disease. The most important attributes were expertise and familiarity of doctors with patients' medical history; distance traveled was least likely to influence patient preferences. The WTP analysis estimated that patients were willing to pay $680 (95% CI, 470-891) for an appointment with a specialist, $571 (95% CI, 388-754) for doctors familiar with their history, $422 (95% CI, 262-582) for shorter waiting times, $399 (95% CI, 249-549) to be accompanied by family/friends, and $301 (95% CI, 162-441) for shorter traveling times. Male patients had a stronger preference for accompaniment by family/friends. The expertise of HCP was the most important attribute for patients regardless of geographic remoteness. CONCLUSIONS: Our study can assist the development of patient-centered health care models that improve patient access to experienced HCPs, support the role of primary care providers during the cancer journey, and educate patients about the roles of non-oncology HCPs to cope with increasing demand for cancer care.

"Cancer 2015": A Prospective, Population-Based Cancer Cohort-Phase 1: Feasibility of Genomics-Guided Precision Medicine in the Clinic.

"Cancer 2015" is a longitudinal and prospective cohort. It is a phased study whose aim was to pilot recruiting 1000 patients during phase 1 to establish the feasibility of providing a population-based genomics cohort. Newly diagnosed adult patients with solid cancers, with residual tumour material for molecular genomics testing, were recruited into the cohort for the collection of a dataset containing clinical, molecular pathology, health resource use and outcomes data. 1685 patients have been recruited over almost 3 years from five hospitals. Thirty-two percent are aged between 61-70 years old, with a median age of 63 years. Diagnostic tumour samples were obtained for 90% of these patients for multiple parallel sequencing. Patients identified with somatic mutations of potentially "actionable" variants represented almost 10% of those tumours sequenced, while 42% of the cohort had no mutations identified. These genomic data were annotated with information such as cancer site, stage, morphology, treatment and patient outcomes and health resource use and cost. This cohort has delivered its main objective of establishing an upscalable genomics cohort within a clinical setting and in phase 2 aims to develop a protocol for how genomics testing can be used in real-time clinical decision-making, providing evidence on the value of precision medicine to clinical practice.

Management of gastric cancer.

BACKGROUND: Gastric cancer is a common disease with a high mortality. OBJECTIVE: This article aims to outline the management options for patients with gastric cancer. DISCUSSION: The mainstay of curative treatment remains surgical resection. The management of early stage gastric cancer is complex with proven benefit of both pre-operative chemotherapy and postoperative chemo-radiotherapy, as well as complex surgical issues and the patient benefits from management by a multidisciplinary team. The most commonly performed operations for gastric cancer are total and subtotal gastrectomy, depending on the location of the tumour and the ability to gain adequate tumour free margins. Common postoperative difficulties include early satiety, postprandial pain and diarrhoea, hypoglycaemic episodes and bile reflux. Adjuvant chemotherapy and radiotherapy has been demonstrated to have a beneficial role in survival. Palliative surgical options are directed at control of symptoms related to bleeding and obstruction. Palliative chemotherapy has been shown to confer a survival benefit, however, with notable toxicity.