ObjectivesOpioid-induced constipation (OIC) can affect up to 63% of all patients with cancer. The objectives of this study were to assess quality of life as well as efficacy and safety of naloxegol, in patients with cancer with OIC.MethodsAn observational study was made of a cohort of patients with cancer and with OIC exhibiting an inadequate response to laxatives and treated with naloxegol. The sample consisted of adult outpatients with a Karnofsky performance status score ≥50. The Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL) and the Patient Assessment of Constipation Symptoms (PAC-SYM) were applied for 3 months.ResultsA total of 126 patients (58.2% males) with a mean age of 61.3 years (range 34–89) were included. Clinically relevant improvements (>0.5 points) were recorded in the PAC-QOL and PAC-SYM questionnaires (p<0.0001) from 15 days of treatment. The number of days a week with complete spontaneous bowel movements increased significantly (p<0.0001) from 2.4 to 4.6 on day 15, 4.7 after 1 month and 5 after 3 months. Pain control significantly improved (p<0.0001) during follow-up. A total of 13.5% of the patients (17/126) presented some gastrointestinal adverse reaction, mostly of mild (62.5%) or moderate intensity (25%).ConclusionsClinically relevant improvements in OIC-related quality of life, number of bowel movements and constipation-related symptoms were recorded as early as after 15 days of treatment with naloxegol in patients with cancer and OIC, with a good safety profile.

ObjectivesNaloxegol is a peripherally acting µ-opioid receptor antagonist (PAMORA) for treatment of opioid-induced constipation (OIC). The main objective was to analyse the long-term efficacy, quality of life (QOL) and safety of naloxegol in patients with cancer in a real-world study.MethodsThis one-year prospective study included patients older than 18 years, with active oncological disease who were under treatment with opioids for pain control and Karnofsky≥50 and OIC with inadequate response to treatment with laxative (s). All the patients received treatment with naloxegol according to clinical criteria. The main efficacy objectives were measured by the patient assessment of constipation QOL questionnaire (PAC-QOL), the PAC symptoms (PAC-SYM), the response rate at day 15, and months 1-3-6-12, and global QOL (EuroQoL-5D-5L).ResultsA total of 126 patients (58.7% males) with a mean age of 61.5 years (95% CI 59.4 to 63.7) were included. PAC-SYM and PAC-QOL total score and all their dimensions improved from baseline (p<0.0001). At 12 months, 77.8% of the patients were responders to naloxegol treatment. Global QOL was conserved from baseline. A total of 28 adverse reactions, mainly gastrointestinal were observed in 15.1% of the patients (19/126), being 75% (21) mild, 17.9% (5) moderate and 7.1% (2) severe. Most adverse reactions (67.9%) appeared the first 15 days of treatment.ConclusionThe results of this first long-term and real-world-data study in patients with cancer, showed the sustained efficacy and safety of naloxegol for the treatment of OIC in this group of patients.

Purpose: To describe the timing of chemotherapy initiation after surgery for Wilms tumor (WT) and neuroblastoma within a dedicated children’s cancer center. Methods: A single-institution retrospective cohort study identified patients that underwent resection of unilateral WT or high-risk neuroblastoma and received adjuvant chemotherapy treatment. Adjuvant chemotherapy initiation and postoperative complications were recorded. Results: Among 47 WT patients, the median time to chemotherapy initiation was 11 days [interquartile range IQR 7-14]. 3 WT patients had post-operative complications, but all preceded chemotherapy. Among 83 patients treated for high-risk neuroblastoma, the median time to chemotherapy was 11 days [IQR 9-14]. High-risk neuroblastoma patients with 30-day postoperative complications had a significantly longer time to initiation of adjuvant chemotherapy (odds ratio 1.13; p=0.008). Many of these complications preceded and delayed the initiation of post-operative chemotherapy. No complications occurred in the group of 12 (25%) WT patients or 16 (19.3%) neuroblastoma patients who started chemotherapy ≤7 days after surgery. Conclusion: There is no association between early initiation of adjuvant chemotherapy and post-operative complications including wound healing. Early initiation of chemotherapy (≤7 days) is feasible in unilateral WT or high-risk neuroblastoma patients who are otherwise doing well without resulting in a preponderance of wound healing complications.

Purpose Identifying patient characteristics that define a worse disease prognosis or “high tumor burden” (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice. Patients and Methods A representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience. Results HTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively. Conclusion In the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.

Background: Worldwide, colorectal cancer (CRC) has the second highest mortality rate of all malignancies. Sequencing efforts on primary CRC (pCRC) have led to extensive knowledge about its genomic landscape. Because the molecular characteristics change over time and under treatment pressure, tumor characteristics of metastases can differ from those of the primary tumor. Therefore, better insight into the genomic alterations of metastatic CRC (mCRC) is key to improve treatment strategies.Methods: We investigated whole genome sequencing (WGS) data of metastases of 429 CRC patients participating in the CPCT-02 study (NCT01855477). Based on prior treatment data, patients were divided into a group who did and a group who did not receive systemic treatment prior to the moment the biopsy was taken. Our sequencing data was compared to publicly available data from pCRC. In addition, observed molecular patterns were associated with pretreatment regimens and clinical outcome. The potential value of WGS analysis for current clinical practice was explored.Results: Compared to pCRC we found that TP53, ZFP36L2, KRAS, and APC were more frequently mutated in mCRC whereas PIK3CA mutations were less frequent. Clear shifts in the relative contributions of mutational signatures were observed in mCRC compared to pCRC. We identified a subgroup of both pretreated and untreated mCRC samples characterized by signatures rarely found in pCRC (SBS9/39/41). Effects of prior treatment were observed in pretreated patients versus untreated patients on the total number of aberrations, mutational signatures, and CNVs. Based on their molecular landscape, 55% of the patients could qualify for on-or off-label FDAapproved targeted treatments. In addition to KRAS/NRAS and BRAF, mutations in FBXW7 were associated with poor response to EGFR-targeted treatments.Conclusions: Differences in driver genes and mutational signatures were observed between mCRC and pCRC, and genomic effects of prior treatment were observed in pretreated mCRC patients versus untreated patients. In conclusion, this study provides an unprecedentedly comprehensive insight into the molecular landscape of mCRC and identifies clinically useful genomic features for future patient management.Clinical trial identification: NCT01855477.