Transforming the oncology data paradigm by creating, capturing, and retrieving structured cancer data at the point of care: A Mayo Clinic pilot.

INTRODUCTION: Structured data capture requires defined languages such as minimal Common Oncology Data Elements (mCODE). This pilot assessed the feasibility of capturing 5 mCODE categories (stage, disease status, performance status (PS), intent of therapy and intent to change therapy). METHODS: A tool (SmartPhrase) using existing and custom structured data elements was Built to capture 4 data categories (disease status, PS, intent of therapy and intent to change therapy) typically documented as free-text within notes. Existing functionality for stage was supported by the Build. Participant survey data, presence of data (per encounter), and time in chart were collected prior to go-live and repeat timepoints. The anticipated outcome was capture of >50% sustained over time without undue burden. RESULTS: Pre-intervention (5-weeks before go-live), participants had 1390 encounters (1207 patients). The median percent capture across all participants was 32% for stage; no structured data was available for other categories pre-intervention. During a 6-month pilot with 14 participants across three sites, 4995 encounters (3071 patients) occurred. The median percent capture across all participants and all post-intervention months increased to 64% for stage and 81%-82% for the other data categories post-intervention. No increase in participant time in chart was noted. Participants reported that data were meaningful to capture. CONCLUSIONS: Structured data can be captured (1) in real-time, (2) sustained over time without (3) undue provider burden using note-based tools. Our system is expanding the pilot, with integration of these data into clinical decision support, practice dashboards and potential for clinical trial matching.

Silmitasertib plus gemcitabine and cisplatin first-line therapy in locally advanced/metastatic cholangiocarcinoma: A Phase 1b/2 study.

BACKGROUND AND AIMS: This study aimed to investigate safety and efficacy of silmitasertib, an oral small molecule casein kinase 2 inhibitor, plus gemcitabine and cisplatin (G+C) versus G+C in locally advanced/metastatic cholangiocarcinoma. APPROACH AND RESULTS: This work is a Phase 1b/2 study (S4-13-001). In Phase 2, patients received silmitasertib 1000 mg twice daily for 10 days with G+C on Days 1 and 8 of a 21-day cycle. Primary efficacy endpoint was progression-free survival (PFS) in the modified intent-to-treat population (defined as patients who completed at least one cycle of silmitasertib without dose interruption/reduction) from both phases (silmitasertib/G+C n = 55, G+C n = 29). The response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. The median PFS was 11.2 months (95% confidence interval [CI], 7.6, 14.7) versus 5.8 months (95% CI, 3.1, not evaluable [NE]) ( p  = 0.0496); 10-month PFS was 56.1% (95% CI, 38.8%, 70.2%) versus 22.2% (95% CI, 1.8%, 56.7%); and median overall survival was 17.4 months (95% CI, 13.4, 25.7) versus 14.9 months (95% CI, 9.9, NE) with silmitasertib/G+C versus G+C. Overall response rate was 34.0% versus 30.8%; the disease control rate was 86.0% versus 88.5% with silmitasertib/G+C versus G+C. Almost all silmitasertib/G+C (99%) and G+C (93%) patients reported at least one treatment emergent adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib/G+C versus G+C were diarrhea (70% versus 13%), nausea (59% vs. 30%), fatigue (47% vs. 47%), vomiting (39% vs. 7%), and anemia (39% vs. 30%). Twelve patients (10%) discontinued treatment because of TEAEs during the study. CONCLUSIONS: Silmitasertib/G+C demonstrated promising preliminary evidence of efficacy for the first-line treatment of patients with locally advanced/metastatic cholangiocarcinoma.

Phase 1 trial of navitoclax and sorafenib in patients with relapsed or refractory solid tumors with hepatocellular carcinoma expansion cohort.

Navitoclax (ABT-263) is an oral BCL2 homology-3 mimetic that binds with high affinity to pro-survival BCL2 proteins, resulting in apoptosis. Sorafenib, an oral multi kinase inhibitor also promotes apoptosis and inhibits tumor angiogenesis. The efficacy of either agent alone is limited; however, preclinical studies demonstrate synergy with the combination of navitoclax and sorafenib. In this phase 1 study, we evaluated the combination of navitoclax and sorafenib in a dose escalation cohort of patients with refractory solid tumors, with an expansion cohort in hepatocellular carcinoma (HCC). Maximum tolerated dose (MTD) was determined using the continual reassessment method. Navitoclax and sorafenib were administered continuously on days 1 through 21 of 21-day cycles. Ten patients were enrolled in the dose escalation cohort and 15 HCC patients were enrolled in the expansion cohort. Two dose levels were tested, and the MTD was navitoclax 150 mg daily plus sorafenib 400 mg twice daily. Among all patients, the most common grade 3 toxicity was thrombocytopenia (5 patients, 20%): there were no grade 4 or 5 toxicities. Patients received a median of 2 cycles (range 1-36 cycles) and all patients were off study treatment at data cut off. Six patients in the expansion cohort had stable disease, and there were no partial or complete responses. Drug-drug interaction between navitoclax and sorafenib was not observed. The combination of navitoclax and sorafenib did not increase induction of apoptosis compared with navitoclax alone. Navitoclax plus sorafenib is tolerable but showed limited efficacy in the HCC expansion cohort. These findings do not support further development of this combination for the treatment of advanced HCC. This phase I trial was conducted under ClinicalTrials.gov registry number NCT01364051.

Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study.

BACKGROUND: HER2 is an actionable target in metastatic colorectal cancer. We assessed the activity of tucatinib plus trastuzumab in patients with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer. METHODS: MOUNTAINEER is a global, open-label, phase 2 study that enrolled patients aged 18 years and older with chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer at 34 sites (clinics and hospitals) in five countries (Belgium, France, Italy, Spain, and the USA). Initially, the study was designed as a single-cohort study, which was expanded following an interim analysis to include more patients. Initially, patients were given tucatinib (300 mg orally twice daily) plus intravenous trastuzumab (8 mg/kg as an initial loading dose, then 6 mg/kg every 21 days; cohort A) for the duration of treatment (until progression), and after expansion, patients were randomly assigned (4:3), using an interactive web response system and stratified by primary tumour location, to either tucatinib plus trastuzumab (cohort B) or tucatinib monotherapy (cohort C). The primary endpoint was confirmed objective response rate per blinded independent central review (BICR) for cohorts A and B combined and was assessed in patients in the full analysis set (ie, patients with HER2-positive disease who received at least one dose of study treatment). Safety was assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT03043313, and is ongoing. FINDINGS: Between Aug 8, 2017, and Sept 22, 2021, 117 patients were enrolled (45 in cohort A, 41 in cohort B, and 31 in cohort C), of whom 114 patients had locally assessed HER2-positive disease and received treatment (45 in cohort A, 39 in cohort B, and 30 in cohort C; full analysis set), and 116 patients received at least one dose of study treatment (45 in cohort A, 41 in cohort B, and 30 in cohort C; safety population). In the full analysis set, median age was 56·0 years (IQR 47-64), 66 (58%) were male, 48 (42%) were female, 88 (77%) were White, and six (5%) were Black or African American. As of data cutoff (March 28, 2022), in 84 patients from cohorts A and B in the full analysis set, the confirmed objective response rate per BICR was 38·1% (95% CI 27·7-49·3; three patients had a complete response and 29 had a partial response). In cohorts A and B, the most common adverse event was diarrhoea (55 [64%] of 86), the most common grade 3 or worse adverse event was hypertension (six [7%] of 86), and three (3%) patients had tucatinib-related serious adverse events (acute kidney injury, colitis, and fatigue). In cohort C, the most common adverse event was diarrhoea (ten [33%] of 30), the most common grade 3 or worse adverse events were increased alanine aminotransferase and aspartate aminotransferase (both two [7%]), and one (3%) patient had a tucatinib-related serious adverse event (overdose). No deaths were attributed to adverse events. All deaths in treated patients were due to disease progression. INTERPRETATION: Tucatinib plus trastuzumab had clinically meaningful anti-tumour activity and favourable tolerability. This treatment is the first US Food and Drug Administration-approved anti-HER2 regimen for metastatic colorectal cancer and is an important new treatment option for chemotherapy-refractory HER2-positive metastatic colorectal cancer. FUNDING: Seagen and Merck & Co.

Patient-reported Adverse Events During Neoadjuvant Therapy in a Phase 2 Borderline Resectable Pancreatic Cancer Clinical Trial (Alliance A021501).

OBJECTIVE: We sought to evaluate symptomatic adverse event (AE) rates among patients with pancreatic cancer receiving neoadjuvant therapy on clinical trial (A021501) using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE). BACKGROUND: To date, pancreatic cancer clinical trials have measured AEs using standard physician reporting [Common Terminology Criteria for Adverse Events (CTCAE)]. Patient-reported symptomatic AEs have been incompletely characterized. METHODS: A021501 (December 31, 2016-January 1, 2019) randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX+hypofractionated radiotherapy (Arm 2), followed by pancreatectomy and adjuvant FOLFOX6. Patients completed PRO-CTCAE assessments at baseline, on day 1 of each chemotherapy cycle, and daily during radiotherapy. RESULTS: Of 126 patients, 96 (76%) initiated treatment and completed a baseline plus at least 1 postbaseline PRO-CTCAE assessment. Diarrhea and fatigue were the only symptomatic grade 3 or higher AEs identified in at least 10% of patients using CTCAE. At least 10% of all patients reported an adjusted PRO-CTCAE composite grade 3 AE during neoadjuvant treatment for 10 of 15 items: anxiety (10%), bloating of abdomen (16%), decreased appetite (18%), diarrhea (13%), dry mouth (21%), fatigue (36%), nausea (18%), generalized pain (16%), abdominal pain (21%), and problems tasting (32%). Decreased appetite was higher in Arm 2 than in Arm 1 ( P =0.0497); no other differences between study arms were observed. CONCLUSION: Symptomatic AEs during neoadjuvant therapy were common and were reported more frequently by patients using PRO-CTCAE than were recorded by clinicians using standard CTCAE.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Baseline Quality of Life is a Strong and Independent Prognostic Factor for Overall Survival in Metastatic Colorectal Cancer.

BACKGROUND: Previous studies have established that higher baseline quality of life (QOL) scores are associated with improved survival in patients with metastatic colorectal cancer (mCRC). We examined the relationship between overall survival (OS) and baseline QOL. PATIENTS AND METHODS: A total of 1 247 patients with mCRC participating in N9741 (comparing bolus 5-FU/LV, irinotecan [IFL] vs infusional 5-FU/leucovorin [LV]/oxaliplatin [FOLFOX] vs. irinotecan/oxaliplatin [IROX]) provided data at baseline on overall QOL using a single-item linear analogue self-assessment (LASA) 0-100 point scale. The association of OS according to clinically deficient (defined as CD-QOL, score 0-50) vs not clinically deficient (nCD-QOL, score 51-100) baseline QOL scores was tested. A multivariable analysis using Cox proportional hazards modeling was performed to adjust for the effects of multiple baseline factors. An exploratory analysis was performed evaluating OS according to baseline QOL status among patients who did or did not receive second-line therapy. RESULTS: Baseline QOL was a strong predictor of OS for the whole cohort (CD-QOL vs nCD-QOL: 11.2 months vs 18.4 months, P < .0001), and in each arm IFL 12.4 vs 15.1 months, FOLFOX 11.1 months vs 20.6 months, and IROX 8.9 months vs 18.1 months. Baseline QOL was associated with baseline performance status (PS) (P < .0001). After adjusting for PS and treatment arm, baseline QOL was still associated with OS (P = .017). CONCLUSIONS: Baseline QOL is an independent prognostic factor for OS in patients with mCRC. The demonstration that patient-assessed QOL and PS are independent prognostic indicators suggests that these assessments provide important complementary prognostic information.

Selecting Optimal First-Line Treatment for Microsatellite Stable and Non-Mutated RAS/BRAF Metastatic Colorectal Cancer.

OPINION STATEMENT: Standard frontline treatment of metastatic colorectal cancer (CRC) is cytotoxic chemotherapy plus a biologic agent such as an anti-EGFR monoclonal antibody (cetuximab or panitumumab) or anti-VEGF antibody (bevacizumab). Predictive biomarkers include mismatch repair (MMR) status, and RAS and BRAF mutation status; and important factors in treatment selection include primary tumor location, intent of therapy, and potential toxicity, as well as patient age, comorbidities, and patient preference. To date, single-, double-, or triple-agent cytotoxic chemotherapy all have important roles in appropriately selected patients, with the addition of anti-VEGF or anti-EGFR antibody therapy based on the relevant predictive biomarker. Data indicate that patients with proficient MMR, RAS/BRAF wt mCRC are candidates for an anti-EGFR antibody plus doublet chemotherapy if they have a left-sided primary tumor, or for anti-VEGF (bevacizumab) plus doublet or triplet chemotherapy if they have a right-sided primary tumor. Future studies may provide more predictive biomarkers to further personalize therapy for this heterogeneous disease.

Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Patients with non-small-cell lung cancer (NSCLC) that is resistant to PD-1 and PD-L1 (PD[L]-1)-targeted therapy have poor outcomes. Studies suggest that radiotherapy could enhance antitumour immunity. Therefore, we investigated the potential benefit of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) inhibition alone or combined with radiotherapy. METHODS: This open-label, multicentre, randomised, phase 2 trial was done by the National Cancer Institute Experimental Therapeutics Clinical Trials Network at 18 US sites. Patients aged 18 years or older with metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression during previous PD(L)-1 therapy were eligible. They were randomly assigned (1:1:1) in a web-based system by the study statistician using a permuted block scheme (block sizes of three or six) without stratification to receive either durvalumab (1500 mg intravenously every 4 weeks for a maximum of 13 cycles) plus tremelimumab (75 mg intravenously every 4 weeks for a maximum of four cycles) alone or with low-dose (0·5 Gy delivered twice per day, repeated for 2 days during each of the first four cycles of therapy) or hypofractionated radiotherapy (24 Gy total delivered over three 8-Gy fractions during the first cycle only), 1 week after initial durvalumab-tremelimumab administration. Study treatment was continued until 1 year or until progression. The primary endpoint was overall response rate (best locally assessed confirmed response of a partial or complete response) and, along with safety, was analysed in patients who received at least one dose of study therapy. The trial is registered with ClinicalTrials.gov, NCT02888743, and is now complete. FINDINGS: Between Aug 24, 2017, and March 29, 2019, 90 patients were enrolled and randomly assigned, of whom 78 (26 per group) were treated. This trial was stopped due to futility assessed in an interim analysis. At a median follow-up of 12·4 months (IQR 7·8-15·1), there were no differences in overall response rates between the durvalumab-tremelimumab alone group (three [11·5%, 90% CI 1·2-21·8] of 26 patients) and the low-dose radiotherapy group (two [7·7%, 0·0-16·3] of 26 patients; p=0·64) or the hypofractionated radiotherapy group (three [11·5%, 1·2-21·8] of 26 patients; p=0·99). The most common grade 3-4 adverse events were dyspnoea (two [8%] in the durvalumab-tremelimumab alone group; three [12%] in the low-dose radiotherapy group; and three [12%] in the hypofractionated radiotherapy group) and hyponatraemia (one [4%] in the durvalumab-tremelimumab alone group vs two [8%] in the low-dose radiotherapy group vs three [12%] in the hypofractionated radiotherapy group). Treatment-related serious adverse events occurred in one (4%) patient in the durvalumab-tremelimumab alone group (maculopapular rash), five (19%) patients in the low-dose radiotherapy group (abdominal pain, diarrhoea, dyspnoea, hypokalemia, and respiratory failure), and four (15%) patients in the hypofractionated group (adrenal insufficiency, colitis, diarrhoea, and hyponatremia). In the low-dose radiotherapy group, there was one death from respiratory failure potentially related to study therapy. INTERPRETATION: Radiotherapy did not increase responses to combined PD-L1 plus CTLA-4 inhibition in patients with NSCLC resistant to PD(L)-1 therapy. However, PD-L1 plus CTLA-4 therapy could be a treatment option for some patients. Future studies should refine predictive biomarkers in this setting. FUNDING: The US National Institutes of Health and the Dana-Farber Cancer Institute.

Pancreatic cancer risk to siblings of probands in bilineal cancer settings.

PURPOSE: Pancreatic cancer (PC) risk is increased in families, but PC risk and risk perception have been understudied when both parents have cancer. METHODS: An unbiased method defining cancer triads (proband with PC and both parents with cancer) in a prospective registry estimated risk of PC to probands' siblings in triad group 1 (no parent with PC), group 2 (1 parent with PC), and group 3 (both parents with PC). We estimated standardized incidence ratios (SIRs) using a Surveillance, Epidemiology, and End Results (SEER) reference. We also estimated the risk when triad probands carried germline pathogenic/likely pathogenic variants in any of the 6 PC-associated genes (ATM, BRCA1, BRCA2, CDKN2A, MLH1, and TP53). PC risk perception/concern was surveyed in siblings and controls. RESULTS: Risk of PC was higher (SIR = 3.5; 95% CI = 2.2-5.2) in 933 at-risk siblings from 297 triads. Risk increased by triad group: 2.8 (95% CI = 1.5-4.5); 4.5 (95% CI = 1.6-9.7); and 21.2 (95% CI = 4.3-62.0). SIR in variant-negative triads was 3.0 (95% CI = 1.6-5.0), whereas SIR in variant-positive triads was 10.0 (95% CI = 3.2-23.4). Siblings' perceived risk/concern of developing PC increased by triad group. CONCLUSION: Sibling risks were 2.8- to 21.2-fold higher than that of the general population. Positive variant status increased the risk in triads. Increasing number of PC cases in a triad was associated with increased concern and perceived PC risk.

A pilot study of Pan-FGFR inhibitor ponatinib in patients with FGFR-altered advanced cholangiocarcinoma.

Background Biliary tract cancers (BTC) are rare, chemo resistant and are associated with a poor prognosis. Preclinical and early clinical work had demonstrated interesting anti-tumor activity from targeting fibroblast growth factor receptor (FGFR) pathway. We hypothesized that ponatinib, a multi-targeted tyrosine kinase inhibitor with activity against FGFR, would be active in BTC patients with FGFR alterations. Methods This was a multi-center, single institution pilot study of ponatinib in patients with advanced, refractory BTC with FGFR alterations. The primary end point was overall response rate, with secondary points of overall survival (OS), progression-free survival (PFS) and Health Related Quality of Life (HRQoL) assessment. Results Twelve patients were enrolled prior to early termination of the trial. Partial responses were observed in 1 from 12 patients. Median PFS was 2.4 months and median OS was 15.7 months. All observed toxicities were manageable and reversible. Toxicities were mild, with lymphopenia (75%), rash (63%) and fatigue (50%) being the most frequent. No significant detriment in global QoL was observed. Conclusions Ponatinib as a single agent in FGFR altered BTC is tolerable with limited clinical activity. This is the first report of prospective assessment of FGFR inhibition in BTC using ponatinib, and the first study to report its effect on HRQoL. Further development of ponatinib will involve correlative studies to better refine patient selection, focus on combinations with other molecular targeted agents, conventional cytotoxic chemotherapy, and studies to better understand mechanisms of treatment resistance.

Phase I study of cediranib, an oral VEGFR inhibitor, in combination with selumetinib, an oral MEK inhibitor, in patients with advanced solid malignancies.

PURPOSE: Targeting the vascular endothelial growth factor (VEGF) pathway improves progression free survival in multiple advanced malignancies but durable responses are uncommon. Inhibition of the VEGF pathway at multiple levels of signal transduction may improve clinical outcomes. Preclinical data with cediranib, an inhibitor of all 3 VEGF receptors, in combination with selumetinib, an inhibitor of MEK 1/2, demonstrated improved tumor control experimentally. This phase I trial was designed to test the two agents in combination to evaluate the tolerability, safety and assess disease response. METHODS: Patients with advanced solid malignancies were enrolled into this phase I trial. Cediranib and selumetinib were dosed using a toxicity-adaptive isotonic design for the dose escalation/de-escalation of each agent. Both cediranib and selumetinib were administered daily and continuously. Cycles were 28 days in length. RESULTS: Eighteen patients were enrolled. At all dose levels, dose limiting toxicities (DLT) were observed, which limited dose escalation and further evaluation. The maximum tolerated dose of cediranib and selumetinib in combination could not be determined. The best response of stable disease was observed in eight patients. CONCLUSIONS: Cediranib and selumetinib in combination on a continuous schedule was not tolerable, with patients experiencing cardiovascular and other DLTs. Intermittent schedules may be needed to establish a safe and tolerable combination of cediranib and selumetinib.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

A feasibility study of virtual group therapy to improve quality of life of cancer caregivers.

BACKGROUND: Cancer caregiving can negatively impact the quality of life (QOL) of the caregiver. In-person interventions for improving coping skills have been shown to be effective in improving QOL for caregivers. OBJECTIVES: This pilot project explored the feasibility and acceptability of a virtual group therapy intervention to improve short-term cancer caregiver QOL. METHODS: Caregivers of cancer patients were enrolled in a structured multidisciplinary intervention of eight virtual group therapy sessions provided over four weeks between September 9, 2013 and November 17, 2014. Group sessions were led by trained facilitators and included components of physical therapy, occupational therapy, psychosocial education, cognitive-behavioral intervention, supportive discussion, spiritual reflection, and mindfulness therapy. Feasibility was based on acceptable number of recruited participants per session; acceptability was defined using attendance and 80% QOL completion rates. QOL domains and symptom burden were assessed using validated single items. RESULTS: The 20 cancer caregivers who enrolled were mostly older (80% were ≥ 65 years), female (76.5%), married to the patient (88.2%), Caucasian (100%), and highly educated (100%). 60% attended one to five sessions, 15% attended six to eight sessions, and 25% attended no sessions. Thirty percent completed pre- and post- intervention ratings of QOL items. SIGNIFICANCE OF RESULTS: Findings suggested that a virtual group therapy intervention is feasible for the cancer caregivers in this study. Although not statistically significant, the caregivers reported higher QOL and less symptom burden in multiple domains after participating in the virtual group therapy intervention.

Phase IB study of sorafenib and evofosfamide in patients with advanced hepatocellular and renal cell carcinomas (NCCTG N1135, Alliance).

Background Sorafenib (Sor) remains a first-line option for hepatocellular carcinoma (HCC) or refractory renal cell carcinomas (RCC). PLC/PRF/5 HCC model showed upregulation of hypoxia with enhanced efficacy when Sor is combined with hypoxia-activated prodrug evofosfamide (Evo). Methods This phase IB 3 + 3 design investigated 3 Evo dose levels (240, 340, 480 mg/m2 on days 8, 15, 22), combined with Sor 200 mg orally twice daily (po bid) on days 1-28 of a 28-day cycle. Primary objectives included determining maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Sor + Evo. Results Eighteen patients were enrolled (median age 62.5 years; 17 male /1 female; 12 HCC/6 RCC) across three dose levels (DL0: Sor 200 mg bid/Evo 240 mg/m2 [n = 6], DL1:Sor 200 mg bid/Evo 480 mg/m2 [n = 5], DL1a: Sor 200 mg bid/Evo 340 mg/m2 [n = 7]). Two dose-limiting toxicities (DLTs) were reported with Evo 480 mg/m2 (grade 3 mucositis, grade 4 hepatic failure). Grade 3 rash DLT was observed in one patient at Evo 240 mg/m2. No DLTs were observed at Evo 340 mg/m2. MTD and RP2D were established as Sor 200 mg/Evo 340 mg/m2 and Sor 200/Evo 240 mg/m2, respectively. The most common treatment-related adverse events included fatigue, hand-foot syndrome, hypertension, and nausea/vomiting. Two partial responses were observed, one each at DL0 and DL1a.; disease control rate was 55%. Conclusions RP2D was established as sorafenib 200 mg bid + Evo 240 mg/m2. While preliminary anti-tumor activity was observed, future development must account for advances in immunotherapy in HCC/RCC.

NCCN Guidelines® Insights: Older Adult Oncology, Version 1.2021.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.

Considerations in the management of younger patients with colorectal cancer.

The incidence of colorectal cancer in patients ages 18 to 49 years has increased by 51% throughout the past 3 decades. In the United States, recent guidelines lowered the initial screening age to 45 years. More than 75% of colorectal tumors in younger patients are diagnosed based on the onset of symptoms, such as rectal bleeding, abdominal pain, weight loss, or anemia. In most cases, these individuals do not have a family history of colorectal cancer. On average, the diagnosis of colorectal cancer in younger patients occurs from 6 months to several years after symptoms first arise. As a result, younger patients diagnosed with colorectal cancer tend to present with advanced disease. If a younger patient does not have any contraindications, it is appropriate to consider treatment with a triplet chemotherapy combined with a biologic. The impact of treatment can be greater for younger patients than for older individuals. Even mild or moderate toxicities can strongly impact their daily lives. Younger patients with colorectal cancer are likely to have a higher risk for long-term treatment-related sequelae, particularly because they tend to present with advanced disease and will receive therapy for a prolonged period.

Role of Surgery and Perioperative Therapy in Older Patients with Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: It is unclear whether results from recent trials of resectable pancreatic ductal adenocarcinoma (PDAC) are generalizable to older patients, who are underrepresented. We aimed to evaluate outcomes of surgery and of neoadjuvant and adjuvant therapy in older patients with resectable PDAC. PATIENTS AND METHODS: We included patients aged ≥65 years with upfront resectable PDAC from a prospectively maintained pancreatic cancer registry from 2007 to 2016. Patients were stratified into ages 65-75 and 75+ years. Overall survival (OS) was assessed in treatment comparisons: (A) surgery (n = 636) versus nonsurgical (n = 178), (B) neoadjuvant therapy (n = 139) versus upfront surgery (n = 497), and (C) adjuvant therapy (n = 379) versus surgery alone (n = 118). We compared neoadjuvant (n = 139) versus adjuvant therapy (n = 379) in an exploratory analysis. RESULTS: Nine hundred and three patients had a median age of 73.7 (range, 65-96.6) years. Median OS was 26.6 versus 11.9 months (adjusted hazard ratio [HRadj ], 0.4; 95% confidence interval [CI], 0.31-0.52; p < .001) in Comparison A groups, 30.7 versus 25.8 months (HRadj , 0.69; 95% CI, 0.49-0.96; p = .03) in Comparison B groups, and 26.9 versus 17.4 months (HRadj , 0.62; 95% CI, 0.44-0.88; p = .008) in Comparison C groups, respectively. OS benefit in these treatment comparisons was present in age group 75+ with HRadj 0.24 (95% CI, 0.16-0.36; p < .001) in Comparison A and HRadj 0.52 (95% CI, 0.27-1; p = .049) in Comparison B, but not in Comparison C with HRadj 0.68 (95% CI, 0.43-1.08; p = .1). Statistically comparable median OS of patients who received neoadjuvant or adjuvant therapy stratified by age groups was observed. CONCLUSION: Older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. IMPLICATIONS FOR PRACTICE: Older patients with resectable pancreatic ductal adenocarcinoma (PDAC) in general are underrepresented in large clinical trials and less well studied in terms of the role of surgery, neoadjuvant therapy, and adjuvant therapy. This study collected data on older patients with resectable PDAC from a prospectively maintained single-institutional pancreatic cancer registry of a tertiary referral center from 2007 to 2016. It was found that, with multidisciplinary evaluation, older patients with resectable PDAC who received surgery, neoadjuvant therapy, or adjuvant therapy appeared to have improved survival outcomes compared with those who did not receive such treatment. These results are of substantial importance to practitioners who treat older patients, who are traditionally underrepresented in most clinical trials.

NCCN Guidelines Insights: Rectal Cancer, Version 6.2020.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E- or HER2 amplification-positive disease.