Search

PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with various solid tumors with germline or somatic BRCA1/2 mutations treated with talazoparib are reported. METHODS: Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Patients with germline BRCA -mutated human epidermal growth factor receptor 2–negative locally advanced or metastatic breast cancer were not eligible for this study. Primary end point was disease control (DC) determined by investigator assessment of objective response (OR) or stable disease (SD) of at least 16 weeks duration (SD16+). The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = 0.82; α =.10). Secondary end points were OR, progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS: Twenty-eight patients (20 cancer types) with BRCA1/2 mutations were enrolled from December 2019 to September 2021 and collapsed into a single histology pooled cohort for analysis. All patients were evaluable for efficacy. One complete response, nine partial response, and six SD16+ were observed for DC and OR rates of 57% (one-sided 90% CI, 43 to 100) and 36% (95% CI, 19 to 56), respectively. The null hypothesis of a 15% DC rate was rejected (P <.001). Patients with OR had the following tumor types: breast (2), nonmelanoma skin, mesothelioma, stomach, uterus, non–small cell lung cancer, ovary, hepatocellular carcinoma, and pancreas. Thirteen patients had at least one grade 3-5 adverse event (AE) or serious AE at least possibly related to talazoparib. All were consistent with the drug label except bilirubin increase and hyponatremia (both grade 3 AEs). CONCLUSION: Talazoparib demonstrated antitumor activity in patients with advanced solid tumors and BRCA1/2 mutations, including cancer types for which poly ADP-ribose polymerase inhibitors are not yet US Food and Drug Administration–approved. Talazoparib showed activity in patients with BRCA-mutated tumors for which PARP inhibitors are not yet FDA-approved. @ASCO #TAPUR [ABSTRACT FROM AUTHOR]

PURPOSE: TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with BRAF mutations treated with cobimetinib (C) plus vemurafenib (V) are reported. METHODS: Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with BRAF V600E/D/K/R mutations, and no MAP2K1/2 , MEK1/2 , or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven days off, and V was taken 960 mg orally twice daily. Simon's two-stage design was used with a primary study end point of objective response or stable disease of at least 16 weeks duration. Secondary end points were progression-free survival, overall survival, and safety. RESULTS: Thirty patients were enrolled from August 2016 to August 2018; all had CRC with a BRAF V600E mutation except one patient with a BRAF K601E mutation. Three patients were not evaluable for efficacy. Eight patients with partial responses and six patients with stable disease of at least 16 weeks duration were observed for disease control and objective response rates of 52% (95% CI, 35 to 65) and 30% (95% CI, 14 to 50), respectively. The null hypothesis of 15% disease control rate was rejected (P <.0001). Thirteen patients had at least one grade 3 adverse event or serious adverse event at least possibly related to C + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, and upper gastrointestinal hemorrhage. CONCLUSION: The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations. Cobimetinib + vemurafenib showed a positive signal of activity in patients with colorectal cancer with BRAF mutations @ASCO #TAPUR. [ABSTRACT FROM AUTHOR]

PURPOSE This study assessed the long-term quality of life (QOL) of patients with aggressive lymphoma subtypes treated with autologous hematopoietic cell transplant (autoHCT) compared with those without history of transplant. METHODS Patient-reported QOL measures were prospectively gathered from patients enrolled in the Iowa/Mayo Specialized Program of Research Excellence Molecular Epidemiology Resource cohort with aggressive lymphoma subtypes. QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy-Fatigue Scale, State-Trait Anxiety Inventory (STAI), and Profile of Mood States instruments and with a numeric rating scale for overall QOL and spiritual QOL. The autoHCT group and no HCT groups were compared at 3 years (FU3) and 6 years (FU6) after lymphoma diagnosis. RESULTS In total, 980 patients with lymphoma (106 autoHCT and 874 no HCT) diagnosed between 2002 and 2013 were included for analysis. The mean FACT-G total score was similar in the autoHCT and no HCT groups at FU3 (89.9 v 90.1, P5 .64) and also at FU6 (91.5 v 89.6, P <.44). No differences between the autoHCT and no HCT groups were identified in the FACT subscales. The STAI identified lower anxiety in the autoHCT group by mean STAI1 (state) at FU3 (30.1 v 33.4, P<.01) and by mean STAI2 (trait) at FU6 (30.1 v 33.5, P < .02). No other clinically meaningful differences were identified between the two groups using the other QOL instruments. CONCLUSION Patients remaining in remission at 3 and 6 years after diagnosis had a high level of QOL with no significant differences associated with history of treatment with autoHCT. [ABSTRACT FROM AUTHOR]

PURPOSE: The Consumer Assessment of Healthcare Providers and Systems (CAHPS) Cancer Care Survey is a systematic assessment of health care experiences of patients with cancer. It supports comparisons among all cancer treatment settings and modalities. METHODS: Formative research included 16 focus groups with patients receiving treatment and family members; advice from a panel of oncology and quality improvement experts; and interviews with stakeholders representing oncology associations, accredited cancer centers, and community oncology practices. We conducted cognitive tests of the instrument and field tests at six cancer centers and four community oncology practices, after which the survey was finalized and obtained the CAHPS trademark. RESULTS: The survey includes 56 questions that form six core composite measures (Getting Timely Care; Supporting Patient Self-Management; Available to Provide Care and Information; Provider Communication; Care Coordination; and Courteous Office Staff); two single-item measures of family participation in care and interpreter services; and two global ratings of cancer care and the treatment team. Sixteen additional items form three supplemental composite measures: Shared Decision-Making, Keeping Patients Informed, and Access to Care. CONCLUSION: Mail-only, mail-telephone mixed-mode, and Web-mail mixed-mode data collection methods are recommended. The questionnaires and instructions for use are free and available in English and Spanish on the CAHPS Website (www.ahrq.gov/cahps). [ABSTRACT FROM AUTHOR]

PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study identifies signals of antitumor activity of commercially available targeted agents in patients with advanced cancers that harbor genomic alterations known as drug targets. In this article, data from two cohorts of patients with pancreatic and biliary cancers with CDKN2A loss or mutation treated with palbociclib are reported. METHODS: Eligible patients age 12 years and older with advanced measurable or evaluable solid tumors are provided treatment according to protocol-specified genomic matching rules. The primary study end point is objective response or stable disease of at least 16 weeks duration. For each cohort, a Simon two-stage design was used with a futility evaluation after 10 patients. Secondary end points include safety, progression-free survival (PFS), and overall survival (OS). RESULTS: Between July 2016 and November 2017, 12 and 10 patients with pancreatic and biliary cancer, respectively, with CDKN2A loss or mutation were treated with palbociclib. Twenty evaluable patients (10 per cohort) were included in the analysis. No patients had objective response or stable disease at 16 weeks, and both cohorts were closed. Two patients, neither with response, were determined to be ineligible. All patients were evaluated for safety, PFS, and OS. A median PFS of 7.2 weeks (90% CI, 4.0 to 8.0 weeks) and median OS of 12.4 weeks (90% CI, 4.7 to 23.1 weeks) were observed in the pancreatic cohort. A median PFS of 7.3 weeks (90% CI, 3.9 to 7.9 weeks) and median OS of 11.1 weeks (90% CI, 5.1 to 14.0 weeks) were observed in the biliary cohort. No unexpected toxicities were observed. CONCLUSION: Palbociclib monotherapy does not have clinical activity in patients with advanced pancreatic or biliary cancers with CDKN2A loss or mutation. Toxicity is similar to reported experience with palbociclib in other tumor types. [ABSTRACT FROM AUTHOR]

Purpose: Case reports and small prospective trials suggest that administering targeted therapies to patients with advanced cancer and an identified genomic target may be associated with clinical benefit. The Targeted Agent and Profiling Utilization Registry (TAPUR) study, a phase II prospective, nonrandomized, multibasket pragmatic clinical trial, aims to identify signals of drug activity when US Food and Drug Administration–approved drugs are matched to prespecified genomic targets in patients with advanced cancer, outside of approved indications. Methods: Patients eligible to participate in TAPUR are age ≥ 12 years and have advanced measurable or evaluable solid tumors, multiple myeloma, or B-cell non-Hodgkin lymphoma. Eligible participants are matched to any of the 16 US Food and Drug Administration–approved study drugs based on protocol-specified genomic inclusion and exclusion criteria. Genomic profiling from any Clinical Laboratory Improvement Amendments–certified, College of American Pathologists–accredited laboratory is acceptable. The treating physician selects the treatment from the available study therapies or consults with the TAPUR Molecular Tumor Board. Participants are placed into multiple parallel cohorts defined by tumor type, genomic alteration, and drug. The primary study end point within each cohort is objective response or stable disease of at least 16 weeks duration. Secondary end points include safety, progression-free survival, and overall survival. Results: More than 1,000 participants have thus far been registered, and more than 800 have been treated with a TAPUR study drug. Two study cohorts have permanently closed to enrollment because of lack of antitumor activity, and 12 have expanded to the second stage of enrollment after promising preliminary activity. Conclusion: The TAPUR study will describe the efficacy and toxicity of the targeted drugs used outside of their approved indications when matched to a somatic genomic variant. [ABSTRACT FROM AUTHOR]

Purpose Several studies have demonstrated that patients have a poor understanding of prognosis, survival and effectiveness of chemotherapy, particularly in the setting of advanced cancer. This study examines oncology patient's understanding of their illness based on accurate reporting of stage at diagnosis and knowledge of cancer status (ie, free of cancer or in remission v active disease). Materials and Methods Two hundred eight patients with cancer previously treated at our large community-based cancer institute participated in the Consumer-Based Cancer Care Value Index field survey. Electronic medical record documentation of stage at diagnosis and cancer status was compared with patient's self-reported responses. Concordance of responses and variables influencing discordance were evaluated. Results In 51.0% of patients, self-reported cancer stage matched the abstracted stage, with the highest concordance in patients with advanced cancer (72%) versus patients with stage I to III disease (36.4% to 61.5%). Unexpectedly, discordance was lower among patients with advanced cancer compared with patients with stage I to III cancer (P=.0528). Patients who were concordant for cancer stage at diagnosis were significantly more likely to be female (P=.001), be younger than age 65 years (P=.01), have an income.$60,000 (P=.03) and have more education (P=.02). In 64.4% of patients, self-reported cancer status (ie, free of cancer or in remission v active disease) matched the abstracted status. Nearly 30% of patients were not sure about their status, even when they were free of cancer or in remission. Conclusion Our findings confirm that more than one quarter of patients with advanced cancer have poor illness understanding and highlight that an even greater number of patients with early stage I to III cancer have poor illness understanding. These observations highlight the need to improve illness understanding for patients across the entire cancer continuum. [ABSTRACT FROM AUTHOR]

Purpose: Case reports and small prospective trials suggest that administering targeted therapies to patients with advanced cancer and an identified genomic target may be associated with clinical benefit. The TAPUR Study, a phase II, prospective, non-randomized, multi-basket, pragmatic clinical trial aims to identify signals of drug activity when Food and Drug Administration (FDA) approved drugs are matched to pre-specified genomic targets in patients with advanced cancer, outside of approved indications., Methods: Patients eligible to participate in TAPUR are ages 12 years and older, with advanced, measurable or evaluable solid tumors, multiple myeloma or B cell non-Hodgkin lymphoma. Eligible participants are matched to any of the sixteen FDA approved study drugs based on protocol specified genomic inclusion and exclusion criteria. Genomic profiling from any Clinical Laboratory Improvement Amendments certified, College of American Pathologists accredited laboratory is acceptable. The treating physician selects the treatment from the available study therapies, or consults with the TAPUR Molecular Tumor Board. Participants are placed into multiple parallel cohorts defined by tumor type, genomic alteration and drug. The primary study endpoint within each cohort is objective response or stable disease of at least 16 weeks duration. Secondary endpoints include safety, progression-free survival and overall survival., Results: More than 1000 participants have thus far been registered and more than 800 treated with a TAPUR study drug. Two study cohorts have permanently closed to enrollment due to lack of anti-tumor activity and 12 have expanded to the second stage of enrollment due to promising preliminary activity., Conclusion: The TAPUR Study will describe the efficacy and toxicity of the targeted drugs used outside of their approved indications when matched to a somatic genomic variant.

Purpose: To identify opportunities for improving care, we evaluated patients' perceptions of the quality of their cancer care by race, ethnicity, and language., Patients and Methods: We surveyed a population-based cohort of 1,067 patients with colorectal cancer in northern California approximately 9 months after diagnosis. Adjusting for clinical and demographic factors, mean problem scores were analyzed on a 100-point scale for six domains of care., Results: Mean problem scores were highest for health information (47.8), followed by treatment information (32.3), psychosocial care (31.7), coordination of care (21.3), confidence in providers (13.1), and access to cancer care (12.7). In adjusted comparisons with white patients, African American patients reported more problems with coordination of care (difference, 9.8; P < .001), psychosocial care (difference, 7.2; P = .03), access to care (difference, 6.6; P = .03), and health information (difference, 12.5; P < .001). Asian/Pacific Islander patients reported more problems than did white patients with coordination of care (difference, 13.2; P < .001), access to care (difference, 15.5; P < .001), and health information (difference, 12.6; P = .004). Hispanic patients tended to report more problems with coordination of care (difference, 4.4; P = .06), access to care (difference, 5.8; P = .08), and treatment information (difference, 7.0; P = .06). Non-English-speaking white patients reported more problems than other white patients with coordination of care (difference, 21.9; P < .001), psychosocial care (difference, 16.1; P = .009), access to care (difference, 19.8; P = .003), and treatment information (difference, 17.8; P = .002). Non-English-speaking Hispanic patients reported more problems than other Hispanic patients with confidence in providers (difference, 16.9; P = .01)., Conclusion: Efforts to improve patients' experiences with cancer care should address disparities by race, ethnicity, and language, particularly in coordination of care, access to care, and the provision of relevant information.