Cetuximab Alone or With Irinotecan for Resistant KRAS-, NRAS-, BRAF- and PIK3CA-wild-type Metastatic Colorectal Cancer: The AGITG Randomized Phase II ICECREAM Study.

BACKGROUND: The Irinotecan Cetuximab Evaluation and Cetuximab Response Evaluation (ICECREAM) study assessed the efficacy of cetuximab monotherapy compared with cetuximab combined with chemotherapy for quadruple wild-type (KRAS, NRAS, BRAF, or P13KCA exon 20) metastatic colorectal cancer. PATIENTS AND METHODS: Patients were enrolled in an open-label, multicenter, phase II trial and randomly assigned to cetuximab 400 mg/m2, then 250 mg/m2 cetuximab weekly, with or without irinotecan 180 mg/m2 every 2 weeks. The primary endpoint was 6-month progression-free survival; secondary endpoints were response rate, overall survival, toxicity, and quality of life. RESULTS: From 2012 to 2016, 48 patients were recruited. Two were ineligible, and 2 were not evaluable for response. Characteristics were balanced, except gender (male, 62% vs. 72%) and primary sidedness (left, 95% vs. 68%). For cetuximab compared with cetuximab-irinotecan, progression-free survival was 14% versus 41% (hazard ratio, 0.39; 95% confidence interval, 0.20-0.78; P = .008); response rate was 10% (2 partial responses) versus 38% (1 complete, 8 partial); P = .04. Grade 3 to 4 toxicities were less with cetuximab monotherapy (23% vs. 50%); global and specific quality of life scores did not differ. CONCLUSION: In comparison with cetuximab alone, cetuximab plus irinotecan increases the response rate and delays progression in irinotecan-resistant RAS wild-type colorectal cancer. This echoes data from molecularly unselected patients.

Oncologist provision of smoking cessation support: A national survey of Australian medical and radiation oncologists.

AIM: Continued smoking in patients diagnosed with cancer affects treatment outcomes and overall survival. With national surveys of Australian medical oncologists (MO) and radiation oncologists (RO) we sought to determine current clinical practices, preferences and barriers in providing patient smoking cessation support. METHODS: Oncologist members of the Medical Oncology Group of Australia (n = 452) and Trans-Tasman Radiation Oncology Group (n = 230) were invited to participate in a multiple choice survey exploring smoking cessation practices and beliefs. RESULTS: The survey response rate was 43%. At first consultations more than 90% of MO and RO regularly asked patients if they smoke or use tobacco products, closely followed by documentation of duration of smoking history and current level of consumption. Less common was asking the patient if they intended to quit (MO 63%, RO 53%) and advising cessation (MO 70%, RO 72%). Less than 50% of oncologists regularly asked about current smoking in follow-up consultations. Although a range of referral options for smoking cessation care were used by oncologists, only 2% of MO and 3% of RO actively managed the patients' smoking cessation themselves and this was the least preferred option. The majority believed they require more training in cessation interventions (67% MO, 57% RO) and cited multiple additional barriers to providing cessation care. CONCLUSIONS: Oncologists strongly prefer smoking cessation interventions to be managed by other health workers. A collaborative approach with other health professionals is needed to aid the provision of comprehensive smoking cessation care tailored to patients with cancer.

Impact of regular aspirin use on overall and cancer-specific survival in patients with colorectal cancer harboring a PIK3CA mutation.

BACKGROUND: Recent data have suggested that regular aspirin use improves overall and cancer-specific survival in the subset of colorectal cancer (CRC) patients harboring PIK3CA mutations. However, the number of PIK3CA-mutated CRC patients examined in these studies was modest. Our collaborative study aims to validate the association between regular aspirin use and survival in patients with PIK3CA-mutated CRC. PATIENTS AND METHODS: Patients with PIK3CA-mutated CRC were identified at Moffitt Cancer Center (MCC) in the United States and Royal Melbourne Hospital (RMH) in Australia. Prospective clinicopathological data and survival data were available. At MCC, PIK3CA mutations were identified by targeted exome sequencing using the Illumina GAIIx Next Generation Sequencing platform. At RMH, Sanger sequencing was utilized. Multivariate survival analyses were conducted using Cox logistic regression. RESULTS: From a cohort of 1487 CRC patients, 185 patients harbored a PIK3CA mutation. Median age of patients with PIK3CA-mutated tumors was 72 years (range: 34-92) and median follow up was 54 months. Forty-nine (26%) patients used aspirin regularly. Regular aspirin use was not associated with improved overall survival (multivariate HR 0.96, p = 0.86). There was a trend towards improved cancer-specific survival (multivariate HR 0.60, p = 0.14), but this was not significant. CONCLUSIONS: Despite examining a large number of patients, we did not confirm that regular aspirin use was associated with statistically significant improvements in survival in PIK3CA-mutated CRC patients. Prospective evaluation of this relationship is warranted.

PIK3CA and PTEN gene and exon mutation-specific clinicopathologic and molecular associations in colorectal cancer.

PURPOSE: PIK3CA and PTEN mutations are prevalent in colorectal cancer and potential markers of response to mitogen-activated protein/extracellular signal-regulated kinase inhibitors and anti-EGF receptor antibody therapy. Relationships between phosphoinositide 3-kinase (PI3K) pathway mutation, clinicopathologic characteristics, molecular features, and prognosis remain controversial. EXPERIMENTAL DESIGN: A total of 1,093 stage I-IV colorectal cancers were screened for PIK3CA (exons 9 and 20), KRAS (codons 12-13), BRAF (codon 600) mutations, and microsatellite instability (MSI). PTEN (exons 3-8) and CpG island methylator phenotype (CIMP) status were determined in 744 and 489 cases. PIK3CA data were integrated with 17 previous reports (n = 5,594). RESULTS: PIK3CA and PTEN mutations were identified in 11.9% and 5.8% of colorectal cancers. PTEN mutation was associated with proximal tumors, mucinous histology, MSI-high (MSI-H), CIMP-high (CIMP-H), and BRAF mutation (P < 0.02). PIK3CA mutation was related to older age, proximal tumors, mucinous histology, and KRAS mutation (P < 0.04). In integrated cohort analysis, PIK3CA exon 9 and 20 mutations were overrepresented in proximal, CIMP-low (CIMP-L), and KRAS-mutated cancers (P ≤ 0.011). Comparing PIK3CA exonic mutants, exon 20 mutation was associated with MSI-H, CIMP-H, and BRAF mutation, and exon 9 mutation was associated with KRAS mutation (P ≤ 0.027). Disease-free survival for stage II/III colorectal cancers did not differ by PI3K pathway status. CONCLUSION: PI3K pathway mutation is prominent in proximal colon cancers, with PIK3CA exon 20 and PTEN mutations associated with features of the sessile-serrated pathway (MSI-H/CIMP-H/BRAF(mut)), and PIK3CA exon 9 (and to a lesser extent exon 20) mutation associated with features of the traditional serrated pathway (CIMP-L/KRAS(mut)) of tumorigenesis. Our data highlight the PI3K pathway as a therapeutic target in distinct colorectal cancer subtypes.

Current hepatitis B screening practices and clinical experience of reactivation in patients undergoing chemotherapy for solid tumors: a nationwide survey of medical oncologists.

PURPOSE: Universal screening for chronic hepatitis B virus (HBV) before chemotherapy has been recommended by the Centers for Disease Control. We sought to determine the practice of Australian oncologists with regard to HBV screening in patients with solid tumors (STs) and their clinical experience of HBV reactivation (HBVR). METHODS: A survey was sent to all consultant members of the Medical Oncology Group of Australia. One hundred eighty-eight responses (63% response rate) were received. We also reviewed the incidence of HBV in patients with STs screened at the Peter MacCallum Cancer Centre (Melbourne, Australia). RESULTS: Fifty-three percent of medical oncologists screen for HBV, but only 19% screen all patients. The most common reasons given for performing screening were anecdotal experience of HBVR (46%) and perceived sufficient evidence for screening of some patient subgroups (42%). Sixty-five percent of those who screened did so only in subgroups, usually selecting patients on the basis of ethnicity (82%). Oncologists who did not screen most commonly cited inadequate evidence for a benefit of screening (72%). Twenty-two percent of oncologists had witnessed one or more HBVR events, representing one event per 45 years of respondents' practice. HBVR events reported (n = 54) consisted of asymptomatic liver test abnormalities only (44%), symptomatic hepatitis (28%), decompensated liver failure (19%), and death (7%). In 206 patients with STs screened for HBV, 1.0% (n = 2) were HBV surface antigen positive, and 14.9% hepatitis B core antibody positive. CONCLUSION: The majority of Australian medical oncologists have not adopted universal HBV screening before chemotherapy. Further evidence of the benefit and cost effectiveness of universal screening in patients with STs will be required to alter practice.

Cost-effectiveness of universal hepatitis B virus screening in patients beginning chemotherapy for solid tumors.

PURPOSE: Universal screening for chronic hepatitis B virus (HBV) infection before chemotherapy has been recommended. We evaluated the cost-effectiveness of HBV screening before chemotherapy given for nonhematopoietic solid tumors (STs). METHODS: A decision-analytic model was used to compare the cost-effectiveness of universal screening conducted per professional guidelines versus no screening in hypothetical patient cohorts beginning adjuvant chemotherapy for early breast cancer or palliative chemotherapy for advanced non-small-cell lung cancer. Survival times were extrapolated using Markov models. Probabilities were derived from published studies and costs estimated from the perspective of the Australian health care system. One-way and probabilistic sensitivity analyses were performed, including with the application of an alternative HBV screening strategy. RESULTS: Using an incremental cost-effectiveness ratio threshold of $50,000 (Australian dollars) per life-year (LY) saved, universal HBV screening was not cost-effective for adjuvant patients ($88,224/LY, 13% probability of being cost-effective), palliative patients ($1,344,251/LY, 0%), or pooled (all) patients ($149,857/LY, 1%). Sensitivity analyses found that screening approached cost-effectiveness among adjuvant patients with the highest reported rates of undiagnosed chronic HBV (65%, $59,445/LY) or HBV reactivation with chemotherapy (41%, $56,537/LY). Cost- effectiveness was also significantly influenced by HBV population prevalence. An alternative screening strategy using hepatitis B surface antigen testing only produced the most economically favorable results, with $30,126/LY (80% probability) for adjuvant patients and $51,201/LY (43%) for the pooled cohort. CONCLUSION: Universal HBV screening conducted per current guidelines is not cost-effective in patients with STs. Screening may be economically favorable in selected patient subpopulations and/or with simplification of the screening strategy.

Changes in medical oncology admissions for the management of breast cancer complications: an Australian institution's experience.

AIMS: There is a scarcity of data regarding medical hospitalizations for breast cancer. The aim was to determine whether the burden of inpatient care for breast cancer was declining. METHODS: A retrospective study was conducted of all admissions to a single medical oncology inpatient unit in 1996 and 2006 related to the treatment of breast cancer. The total number of hospitalizations, patients' length of stay in hospital, clinical indications for hospitalization and utilization of inpatient services were determined. Data analysis involved pairwise comparisons between the cohorts. RESULTS: The total number of breast cancer hospitalizations was similar in 1996 and 2006. However, the number of hospitalizations for adjuvant treatment complications was 50% lower in 2006, attributable to a lower rate of chemotherapy-associated febrile neutropenia. Acute clinical problems necessitating inpatient care differed between 1996 and 2006. Fewer hospitalizations for symptomatic hypercalcemia, uncontrolled pain and chemotherapy toxicity were required in 2006 but a significant increase was seen in central nervous system complications. Recent practice involved greater inpatient consultation of other medical and surgical teams. There was a trend towards a shorter duration of admissions in 2006 in both adjuvant and metastatic patients. CONCLUSION: Although total annual breast cancer admission numbers and length of stay did not change significantly, hospitalization for treatment-related complications was less frequent in 2006. The clinical manifestations of metastatic breast cancer appear to be changing, and in our institution are being managed with broader multidisciplinary care.