Objectives
To report stage‐specific patterns of treatment and the influence of management and treatment type on survival rates for people newly diagnosed with small cell lung cancer (SCLC).
Design
...Cross‐sectional patterns of care study; analysis of data prospectively collected for the Victorian Lung Cancer Registry (VLCR).
Setting, participants
All people diagnosed with SCLC in Victoria during 1 April 2011 – 18 December 2019.
Main outcome measures
Stage‐specific management and treatment of people with SCLC; median survival time.
Results
During 2011–19, 1006 people were diagnosed with SCLC (10.5% of all lung cancer diagnoses in Victoria); their median age was 69 years (interquartile range IQR, 62–77 years), 429 were women (43%), and 921 were current or former smokers (92%). Clinical stage was defined for 896 people (89%; TNM stages I–III, 268 30%; TNM stage IV, 628 70%) and ECOG performance status at diagnosis for 663 (66%; 0 or 1, 489 49%; 2–4, 174 17%). The cases of 552 patients had been discussed at multidisciplinary meetings (55%), 377 people had received supportive care screening (37%), and 388 had been referred for palliative care (39%). Active treatment was received by 891 people (89%): chemotherapy, 843 (84%); radiotherapy, 460 (46%); chemotherapy and radiotherapy, 419 (42%); surgery, 23 (2%). Treatment had commenced within fourteen days of diagnosis for 632 of 875 patients (72%). Overall median survival time from diagnosis was 8.9 months (IQR, 4.2–16 months; stage I–III: 16.3 IQR, 9.3–30 months; stage IV: 7.2 IQR, 3.3–12 months). Multidisciplinary meeting presentation (hazard ratio HR, 0.66; 95% CI, 0.58–0.77), multimodality treatment (HR, 0.42; 95% CI, 0.36–0.49), and chemotherapy within fourteen days of diagnosis (HR, 0.68; 95% CI, 0.48–0.94) were each associated with lower mortality during follow‐up.
Conclusion
Rates of supportive care screening, multidisciplinary meeting evaluation, and palliative care referral for people with SCLC could be improved. A national registry of SCLC‐specific management and outcomes data could improve the quality and safety of care.
Purpose of Review
Cardiovascular disease is long-term complication of both cancer and anti-cancer treatment and can have significant ramifications for health-related quality of life and mortality. ...This narrative review explores the current evidence linking cardiovascular disease and cancer, as well as exploring strategies for the prevention and management of cardiovascular disease, and outlines future opportunities in the field of cardio-oncology.
Recent Findings
Cancer confers risk for various cardiovascular diseases including heart failure, cardiomyopathy, arrhythmia, coronary heart disease, stroke, venous thromboembolism, and valvular heart disease. Cancer treatment, in particular agents such as platinum-based chemotherapy, anthracyclines, hormonal treatments, and thoracic radiotherapy, further increases risk. While cardiovascular disease can be identified early and effectively managed in cancer survivors, cardiovascular screening and management does not typically feature in routine long-term cancer care of adult cancer survivors.
Summary
Cancer and cancer treatment can accelerate the development of cardiovascular disease. Further research into screening and management strategies for cardiovascular disease, along with evidence-based guidelines, is required to ensure adult cancer survivors receive appropriate long-term care.
Background
Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumors (GISTs) as at least fourth‐line therapy. In INVICTUS, ripretinib intrapatient dose escalation ...(IPDE) to 150 mg b.i.d. was allowed after progressive disease (PD) on 150 mg QD by blinded independent central review using modified RECIST 1.1. We report the efficacy and safety of ripretinib IPDE to 150 mg b.i.d. after PD among patients randomized to ripretinib 150 mg QD in the INVICTUS study.
Materials and Methods
Tumor imaging was performed every 28‐day cycle for the first four cycles in the ripretinib 150 mg QD period and then every other cycle, including the 150 mg b.i.d. period. Among the ripretinib IPDE patients, progression‐free survival (PFS)1 was the time from randomization until PD; PFS2 was the time from the first dose of ripretinib 150 mg b.i.d. to PD or death.
Results
Among 43 ripretinib IPDE patients, median PFS1 was 4.6 months (95% confidence interval CI, 2.7–6.4) and median PFS2 was 3.7 months (95% CI, 3.1–5.3). Median overall survival was 18.4 months (95% CI, 14.5–not estimable). Ripretinib 150 mg b.i.d. (median duration of treatment 3.7 months) was well tolerated with new or worsening grade 3–4 treatment‐emergent adverse events (TEAEs) of anemia in six (14%) and abdominal pain in three (7%) patients. Ripretinib 150 mg b.i.d. was discontinued because of TEAEs in seven (16%) patients.
Conclusion
Ripretinib 150 mg b.i.d. after PD on 150 mg QD may provide additional clinically meaningful benefit with an acceptable safety profile in patients with at least fourth‐line GISTs.
Implications for Practice
Of the 85 patients with advanced gastrointestinal stromal tumor having received at least three prior anticancer therapies randomized to ripretinib 150 mg once daily (QD) in the phase III INVICTUS study, 43 underwent ripretinib intrapatient dose escalation (IPDE) to 150 mg b.i.d. after progressive disease (PD). Median progression‐free survival was 4.6 months before and 3.7 months after ripretinib IPDE. The safety profile of ripretinib 150 mg b.i.d. was acceptable. These findings indicate ripretinib IPDE to 150 mg b.i.d. may provide additional clinical benefit in patients with PD on ripretinib 150 mg QD, for whom limited treatment options exist.
This article presents further results from the INVICTUS study, focusing on patients who received ripretinib 150 mg QD who received intrapatient dose escalation to 150 mg b.i.d. after progressive disease.
IntroductionGynaecological cancers collectively account for almost 10% of cancer diagnoses made in Australian women. The extent of variation in gynaecological cancer survival rates and treatment ...outcomes across Australia is not well documented. The purpose of the clinical quality registry described in this paper is to systematically monitor and improve quality of care provided to these women, and facilitate clinical process improvements to ensure better patient outcomes and greater adherence to best practice care. The registry infrastructure has been developed in conjunction alongside the inaugural ovarian, tubal and peritoneal (OTP) module, allowing for concurrent piloting of the methodology and one module. Additional tumour modules will be developed in time to cover the other gynaecological tumour types.Method and analysisThe National Gynae-Oncology Registry (NGOR) aims to capture clinical data on all newly diagnosed cancers of the uterus, ovary, fallopian tubes, peritoneum, cervix, vulva and vagina in Australia with a view to using these data to support improved clinical care and increased adherence to ‘best practice’. Data are sourced from existing clinical databases maintained by clinicians and/or hospital gynaecological cancer units. A pilot phase incorporating only OTP cancers has recently been conducted to assess the feasibility of the registry methodology and assess the support of a quality initiative of this nature among clinicians and other key stakeholders.Ethics and disseminationThe NGOR has received National Mutual Acceptance (NMA) ethics approval from Monash Health Human Research Ethics Committee (HREC), NMA HREC Reference Number: HREC/17/MonH/198. We also have approval from Mercy Health HREC and University of Tasmania HREC. Data will be routinely reported back to participating sites illustrating their performance against measures of agreed best practice. It is through this feedback system that the registry will support changes to quality of care and improved patient outcomes.
Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal ...division between left- and right-sided colorectal cancer is unclear. We investigated transverse colon primary tumor location as a biomarker in mCRC.
Pooled analysis of CCTG/AGITG CO.17 and CO.20 trials of cetuximab in chemotherapy-refractory mCRC. Outcomes of patients with RAS/BRAF wild-type (WT) mCRC from CO.17 and KRAS WT mCRC from CO.20 were analyzed according to location.
A total of 553 patients were analyzed, 32 (5.8%) with cancers from the transverse, 101 (18.3%) from right, and 420 from (75.9%) left colon. Transverse mCRC failed to reach significant benefit from cetuximab versus best supportive care (BSC) for overall survival OS; median, 5.9 vs. 2.1 months; HR, 0.63; 95% confidence interval (CI), 0.28-1.42; P=0.26 and progression-free survival (PFS; median, 1.8 vs. 1.3 months; HR, 0.57; 95% CI, 0.26-1.28; P=0.16). Analyzing exclusively patients randomized to cetuximab, right-sided and transverse had comparable outcomes for OS (median, 5.6 vs. 5.9 months; HR, 0.82; 95% CI, 0.50-1.34; P=0.43) and PFS (median, 1.9 vs. 1.8 months; HR, 0.78; 95% CI, 0.49-1.26; P=0.31). Patients with left-sided mCRC had superior outcomes with cetuximab compared with transverse for OS (median, 9.7 vs. 5.9 months; HR, 0.42; 95% CI, 0.27-0.67; P=0.0002) and PFS (median, 3.8 vs. 1.8 months; HR, 0,49; 95% CI, 0.31-0.76; P=0.001). Location was not prognostic in patients treated with BSC alone.
Transverse mCRC has comparable prognostic and predictive features with right-sided mCRC.
A national, lung cancer screening programme is under consideration in Australia, and we assessed cost-effectiveness using updated data and assumptions.
We estimated the cost-effectiveness of lung ...screening by applying screening parameters and outcomes from either the National Lung Screening Trial (NLST) or the NEderlands-Leuvens Longkanker Screenings ONderzoek (NELSON) to Australian data on lung cancer risk, mortality, health-system costs, and smoking trends using a deterministic, multi-cohort model. Incremental cost-effectiveness ratios (ICERs) were calculated for a lifetime horizon.
The ICER for lung screening compared to usual care in the NELSON-based scenario was AU$39,250 (95% CI $18,150-108,300) per quality-adjusted life year (QALY); lower than the NLST-based estimate (ICER = $76,300, 95% CI $41,750-236,500). In probabilistic sensitivity analyses, lung screening was cost-effective in 15%/60% of NELSON-like simulations, assuming a willingness-to-pay threshold of $30,000/$50,000 per QALY, respectively, compared to 0.5%/6.7% for the NLST. ICERs were most sensitive to assumptions regarding the screening-related lung cancer mortality benefit and duration of benefit over time. The cost of screening had a larger impact on ICERs than the cost of treatment, even after quadrupling the 2006-2016 healthcare costs of stage IV lung cancer.
Lung screening could be cost-effective in Australia, contingent on translating trial-like lung cancer mortality benefits to the clinic.
INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to ...once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations. Therefore, we hypothesized that mutational analysis using circulating tumor DNA (ctDNA) might provide further insight. In this exploratory analysis (N = 362), baseline peripheral whole blood was analyzed by a 74-gene ctDNA next-generation sequencing-based assay. ctDNA was detected in 280/362 (77%) samples with KIT mutations in 213/362 patients (59%). Imatinib-resistant mutations were found in the KIT ATP-binding pocket (exons 13/14) and activation loop (exons 17/18). Mutational subgroup assessment showed 2 mutually exclusive populations with differential treatment effects. Patients with only KIT exon 11 + 13/14 mutations (ripretinib, n = 21; sunitinib, n = 20) had better PFS with sunitinib versus ripretinib (median, 15.0 versus 4.0 months). Patients with only KIT exon 11 + 17/18 mutations (ripretinib, n = 27; sunitinib, n = 25) had better PFS with ripretinib versus sunitinib (median, 14.2 versus 1.5 months). The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KIT exon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501.
Purpose
Despite the benefits of palliative care (PC) in pancreatic cancer, little is known about patients who access PC. This observational study examines the characteristics of patients with ...pancreatic cancer at their first episode of PC.
Methods
First-time, specialist PC episodes captured through the Palliative Care Outcomes Collaboration (PCOC), in Victoria, Australia between 2014 and 2020, for pancreatic cancer, were identified. Multivariable logistic regression analyses examined the impact of patient- and service-level characteristics on symptom burden (measured through patient-reported outcome measures and clinician-rated scores) at first PC episode.
Results
Of 2890 eligible episodes, 45% began when the patient was deteriorating and 32% ended in death. High fatigue and appetite-related distress were most common. Generally, increasing age, higher performance status and more recent year of diagnosis predicted lower symptom burden. No significant differences were noted between symptom burden of regional/remote versus major city dwellers; however, only 11% of episodes recorded the patient as a regional/remote resident. A greater proportion of first episodes for non-English-speaking patients began when the patient was unstable, deteriorating or terminal, ended in death and were more likely to be associated with high family/carer problems. Community PC setting predicted high symptom burden, with the exception of pain.
Conclusion
A large proportion of first-time specialist PC episodes in pancreatic cancer begin at a deteriorating phase and end in death, suggesting late access to PC. Timely referrals to community-based specialist PC, access in regional/remote areas, as well as development of culturally diverse support systems require further investigation.
Expanded
mutations have not been assessed as predictive for single-agent cetuximab in metastatic colorectal cancer (mCRC), and low mutant allele frequency (MAF) mutations are of unclear significance. ...We aimed to establish cetuximab efficacy in optimally selected patients using highly sensitive beads, emulsion, amplification, and magnetics (BEAMing) analysis, capable of detecting alterations below standard clinical assays.
CO.17 trial compared cetuximab versus best supportive care (BSC) in
-unselected mCRC. We performed
analysis on microdissected tissue of 242 patients in CO.17 trial using BEAMing for
(codons 12/13/59/61/117/146) and
V600E. Patients without BEAMing but with previous Sanger sequencing-detected mutations were included.
, and
mutations were present in 53%, 4%, and 3% of tumors, respectively. Cetuximab improved overall survival OS; HR, 0.51; 95% confidence interval (CI), 0.32-0.81;
= 0.004 and progression-free survival (PFS; HR, 0.25; 95% CI, 0.15-0.41;
< 0.0001) compared with BSC in
wild-type patients. Cetuximab did not improve OS/PFS for
, or
mutated tumors, and tests of interaction confirmed expanded
(
= 0.0002) and
(
= 0.006) as predictive, while
mutations were not (
= 0.089). BEAMing identified 14% more tumors as
mutant than Sanger sequencing, and cetuximab lacked activity in these patients. Mutations at MAF < 5% were noted in 6 of 242 patients (2%). One patient with a
A59T mutation (MAF = 2%) responded to cetuximab. More
than
mutations were low MAF (OR, 20.50; 95% CI, 3.88-96.85;
= 0.0038).
We establish single-agent cetuximab efficacy in optimally selected patients and show that subclonal
alterations are uncommon and remain of indeterminate significance.
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