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In September 2010, the Cancer and Aging Research Group, in collaboration with the National Cancer Institute and the National Institute on Aging, conducted the first of three planned conferences to discuss research methodology to generate the highest quality research in older adults with cancer and then disseminate these findings among those working in the fields of cancer and aging. Conference speakers discussed the current level of research evidence in geriatric oncology, outlined the current knowledge gaps, and put forth principles for research designs and strategies that would address these gaps within the next 10 years. It was agreed that future oncology research trials that enroll older adults should include: (1) improved standardized geriatric assessment of older oncology patients, (2) substantially enhanced biological assessment of older oncology patients, (3) specific trials for the most vulnerable and/or those older than 75 years, and (4) research infrastructure that specifically targets older adults and substantially strengthened geriatrics and oncology research collaborations. This initial conference laid the foundation for the next two meetings, which will address the research designs and collaborations needed to enhance therapeutic and intervention trials in older adults with cancer. [ABSTRACT FROM AUTHOR]

Randomized phase III trials have established new standards of care for advanced biliary cancer, HER2-positive advanced gastric or gastro-esophageal junction cancer, and preliminarily, for metastatic pancreatic cancer. There is now a validated predictive biomarker to guide use of adjuvant chemotherapy in patients with stage II colon cancer. [ABSTRACT FROM AUTHOR]

To inform clinical trial design and real-world precision pediatric oncology practice, we classified diagnoses, assessed the landscape of mutations, and identified genomic variants matching trials in a large unselected institutional cohort of solid tumors patients sequenced at Dana-Farber / Boston Children's Cancer and Blood Disorders Center. Tumors were sequenced with OncoPanel, a targeted next-generation DNA sequencing panel. Diagnoses were classified according to the International Classification of Diseases for Oncology (ICD-O-3.2). Over 6.5 years, 888 pediatric cancer patients with 95 distinct diagnoses had successful tumor sequencing. Overall, 33% (n = 289/888) of patients had at least 1 variant matching a precision oncology trial protocol, and 14% (41/289) were treated with molecularly targeted therapy. This study highlights opportunities to use genomic data from hospital-based sequencing performed either for research or clinical care to inform ongoing and future precision oncology clinical trials. Furthermore, the study results emphasize the importance of data sharing to define the genomic landscape and targeted treatment opportunities for the large group of rare pediatric cancers we encounter in clinical practice., (© 2024. The Author(s).)

Purpose: Targeted Agent and Profiling Utilization Registry (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. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 ( CDK4 ) amplification treated with palbociclib are reported., Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety., Results: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported., Conclusion: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.

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.

Purpose: Targeted Agent and Profiling Utilization Registry 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 biliary tract cancer (BTC) with ERBB2/3 amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab are reported., Methods: Eligible patients had advanced BTC, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with ERBB2/3 alterations, and a lack of standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16+ weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety., Results: Twenty-nine patients were enrolled from February 2017 to January 2022, and all had advanced BTC with an ERBB2/3 alteration. One patient was not evaluable for efficacy. One complete response, eight partial responses, and two SD16+ were observed for DC and OR rates of 40% (90% CI, 27 to 100) and 32% (95% CI, 16 to 52), respectively. The null hypothesis of 15% DC rate was rejected ( P = .0015). Four patients had at least one grade 3 adverse event (AE) or serious AE at least possibly related to treatment: anemia, diarrhea, infusion-related reaction, and fatigue., Conclusion: Pertuzumab plus trastuzumab met prespecified criteria to declare a signal of activity in patients with BTC and ERBB2/3 amplification, overexpression, or mutation.

The global pharmaceutical industry portfolio is skewed towards cancer and rare diseases due to more predictable development pathways and financial incentives. In contrast, drug development for major chronic health conditions that are responsible for a large part of mortality and disability worldwide is stalled. To examine the processes of novel drug development for common chronic health conditions, a multistakeholder Think Tank meeting, including thought leaders from academia, clinical practice, non-profit healthcare organizations, the pharmaceutical industry, the Food and Drug Administration (FDA), payors as well as investors, was convened in July 2022. Herein, we summarize the proceedings of this meeting, including an overview of the current state of drug development for chronic health conditions and key barriers that were identified. Six major action items were formulated to accelerate drug development for chronic diseases, with a focus on improving the efficiency of clinical trials and rapid implementation of evidence into clinical practice., Competing Interests: Conflict of interest Konstantin A. Krychtiuk: advisory boards Novartis, Sanofi, Amgen; speaker fees Amgen, Daichii Sankyo, Zoll Medical Tomas LG Andersson: employed by AstraZeneca, owns stock in AstraZeneca, travel support by AstraZeneca Ulrike Bodesheim employed by Bayer AG; Javed Butler: Consulting fees: 3ivelabs, Abbott, Amgen, American Regent, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element, Faraday, G3 Pharmaceutical, Imbria, Impulse Dynamics, Innolife, Inventiva, Ionis, Janssen, LivaNova, Lexicon, Medtronic, Merck, Novartis, Novo Nordisk, Otsuka, Occlutech, PharmaCosmos, Roche, Sanofi, Secretome, Sequana, Tricog, Vifor; Speaker Fees: Novartis, Boehringer Ingelheim-Lilly, Astra Zeneca, Impulse Dynamics; Lesley H Curtis: Fees Boehringer Ingleheim, NIH, and Regeneron Pharmaceuticals Mitchell Elkind: Grants: Roche; Lecture Fees: Atria Academy of Science and Medicine; Travel Support: American Heart Association; Adrian F. Hernandez: Consulting fees Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, CSL Behring, Cytokinetics, Eli Lilly, Intellia Therapeutics, Merck, Novartis, Novo Nordisk, Prolaio; Grants/Contracts: American Regent, AstraZeneca, Bayer, Boehringer Ingelheim, Intellia Therapeutics, Merck, Novartis, Novo Nordisk, Verily; Christoph Hornik: None declared; Gary H Lyman: Consulting Fees: Sandoz, Astra Zeneca, Beyond Spring, G1 Therapeutics, Merck, Partners Healthcare, ER Squibb, Samsung, Fresenius Kabi; Pooja Khatri: grants from Cerenovus; serving on the scientific advisory boards of Lumosa; Shionogi, Bayer, and Basking Biosciences; andreceiving online publication royalties from UpToDate; Michael Mbagwu: Stocks in Verana Health as employee Masahiro Murakami: employed by Eli Lilly; Gwen Nichols: None declared; Lothar Roessig: employed by Bayer; Anne Quinn Young: None declared; Richard L. Schilsky Consulting Fees: Cellworks, EQRx, Zephyr AI, Clarified Precision Medicine, Illumina, Member, DSMB, Baseline Study sponsored by Verily Chairman, Scientific Advisory Board, Ontario Institute for Cancer Research Member, Strategic External Advisory Committee for Canadian Cancer Trials Group Chairman, Board of Directors, Reagan-Udall Foundation for the FDA, Member, Board of Directors, Friends of Cancer Research, Member, Board of Directors, Leap Therapeutics; Neha Pagidipati: Research support from Alnylam, Amgen, Boehringer Ingelheim, Eggland's Best, Eli Lilly, Novartis, Novo Nordisk, Verily Life Sciences; Consultation/Advisory Panels for Bayer, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Esperion, AstraZeneca, Merck, Novartis, and Novo Nordisk; Executive Committee member for trials sponsored by Novo Nordisk and by Amgen; DSMB for trials sponsored by J+J and Novartis; Medical advisory board for Miga Health., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Targeted Agent and Profiling Utilization Registry is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with BRAF alterations treated with regorafenib are reported., Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-1, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as investigator assessment of patients with complete or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low accruing histology-specific cohorts with BRAF alterations treated with regorafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, 0.84; α, .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety., Results: Twenty-eight patients with 12 tumor types with BRAF alterations were enrolled from June 2016 to June 2021. All patients were evaluable for efficacy. Two patients with PR and four with SD16+ were observed for DC and OR rates of 21% (90% CI, 12 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected ( P = .24). Eight patients had at least one grade 3 adverse event or serious adverse event at least possibly related to regorafenib., Conclusion: Regorafenib did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with BRAF alterations.

Purpose: With the advent of precision medicine, molecular tumor boards (MTBs) were established to interpret genomic results and guide decision making for targeted therapy in oncology patients. There are currently no universal guidelines for how MTBs should operate and thus variance can be seen depending on which MTB is reviewing the case. This study assesses the concordance of MTB recommendations when a participant case is reviewed by two different MTBs, establishes potential reasons for discordance, and advocates for the establishment of standard MTB operating guidelines., Patients and Methods: Participants with advanced cancer, who had exhausted all standard treatment options were screened for the Targeted Agent and Profiling Utilization Registry (TAPUR) Study. Cases were submitted for MTB review if the treatment proposal was outside the protocol genomic matching rules, or if multiple treatment options were identified. Of the 306 cases submitted for review by the TAPUR MTB from 2016 to 2018, 107 were randomly selected for secondary review by a different MTB group. Recommendations from the original review were not disclosed. Concordance between MTB group recommendations was assessed. Concordance was defined as agreement between MTB reviews on the genomic alteration and study drug match proposed by the clinical site. Thematic qualitative analysis was conducted for the discordant cases to assess reasons for discordance., Results: Complete or partial concordance was observed in 79% of cases (95% CI, 70 to 86; one-sided P = .25). Most discordant analyses were due to disagreements on the strength of evidence regarding efficacy of the proposed treatment (32%)., Conclusion: When presented with identical participant cases, different MTB review groups make the same or similar treatment recommendations approximately 80% of the time.

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 from cohorts of patients with metastatic breast cancer (BC) with FGFR1 and FGFR2 alterations treated with sunitinib are reported., Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease of at least 16 weeks duration (SD16+) according to RECIST v1.1. Secondary end points included OR, progression-free survival, overall survival, duration of response, duration of stable disease, and safety., Results: Forty patients with BC with FGFR1 (N = 30; amplification only n = 26, mutation only n = 1, both n = 3) or FGFR2 (N = 10; amplification only n = 2, mutation only n = 6, both n = 2) alterations were enrolled. Three patients in the FGFR1 cohort were not evaluable for efficacy; all patients in the FGFR2 cohort were evaluable. For the FGFR1 cohort, two patients with partial response and four with SD16+ were observed for DC and OR rates of 27% (90% CI, 13 to 100) and 7% (95% CI, 1 to 24), respectively. The null hypothesis of 15% DC rate was not rejected ( P = .169). No patients achieved DC in the FGFR2 cohort ( P = 1.00). Thirteen of the 40 total patients across both cohorts had at least one grade 3-4 adverse event or serious adverse event at least possibly related to sunitinib., Conclusion: Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either FGFR1 or FGFR2 alterations. Other treatments and clinical trials should be considered for these patient populations.

The conceptual framework of pragmatism in clinical trials is explored using the American Society of Clinical Oncology's pragmatic, non-randomized, phase II, multi-center basket clinical trial, the Targeted Agent and Profiling Utilization Registry Study (NCT02693535) as a model. The Targeted Agent and Profiling Utilization Registry Study aims to identify signals of drug activity when Food and Drug Administration approved drugs are matched to pre-specified genomic targets in patients with advanced cancer outside of their approved indication(s). The objectives of the study are to generate evidence of potential signals of activity in targeted therapies prescribed in an off-label setting as well as to expose and educate community cancer centers to genomic testing and precision medicine through the study protocol. The principles of pragmatic trial design can be applied across a broad spectrum of evidence-generation strategies, from explanatory trials to real-world evidence studies, and are briefly discussed. American Society of Clinical Oncology's Targeted Agent and Profiling Utilization Registry Study falls closer to the pragmatic end of this spectrum as it seeks to assess the efficacy of Food and Drug Administration approved drugs used outside their approved indications under usual care conditions, yielding results generalizable to the population that would likely receive the intervention in practice, while still adhering to rigorous data quality standards. The Targeted Agent and Profiling Utilization Registry Study's pragmatic objectives, characteristics, strengths, and limitations in its implementation are discussed and demonstrate that a large, multi-center, precision medicine basket trial can be mounted in the context of community practice and can generate clinically useful information with minimal burden to patients and clinical trial sites., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: P.K.M., E.G-M., and J.K.P. have nothing to disclose. R.L.S. has received institutional support (ASCO) from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Genentech/Roche, Eli Lilly and Company, Merck & Co., Inc., Pfizer, and Seagen for support of the TAPUR Study; R.L.S. has received consulting fees from Cellworks, Scandion Oncology, Bryologyx, Illumina, EQRx, Syapse, and Zephyr AI; R.L.S. has a leadership of fiduciary role for Clarified Precision Medicine and Leap Therapeutics; and R.L.S. has stock or stock options in EQRx, Clarified Precision Medicine and Leap Therapeutics.

Purpose: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as ≥9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported., Methods: Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD., Results: Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% ( P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths., Conclusion: Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB.

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with ATM mutations treated with nivolumab plus ipilimumab are reported., Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Primary end point was disease control (DC), defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16 weeks duration (SD16+). Low-accruing histology-specific cohorts with ATM mutations treated with nivolumab plus ipilimumab were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated based on a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = .84; α = .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of SD, and safety., Results: Twenty-nine patients with 10 tumor types with ATM mutations were enrolled from January 2018 to May 2020. One patient was not evaluable for efficacy. One CR, three PR, and three SD16+ were observed for DC and OR rates of 24% ( P = .13; one-sided 90% CI: 14 to 100) and 14% (95% CI: 4 to 32), respectively. The null hypothesis of 15% DC rate was not rejected. Eleven patients had one treatment-related grade 3 adverse event (AE) or serious AE. There were two treatment-related patient deaths including immune-related encephalitis and respiratory failure., Conclusion: Nivolumab plus ipilimumab did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with ATM mutations.

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported., Methods: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low-accruing histology-specific cohorts with BRAF mutations treated with cobimetinib plus vemurafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, .82; α, .10). The secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety., Results: Thirty-one patients with solid tumors with BRAF mutations were enrolled. Twenty-eight patients were evaluable for efficacy. Patients had tumors with BRAF V600E (n = 26), K601E (n = 2), or other (n = 3) mutations. Two patients with CR (breast and ovarian cancers; V600E), 14 with PR (13 V600E, one N581I), and three with SD16+ (two V600E, one T599&#95;V600insT) were observed with a DC rate of 68% ( P < .0001; one-sided 90% CI, 54 to 100) and an OR rate of 57% (95% CI, 37 to 76). Nineteen patients experienced ≥one drug-related grade 3-5 adverse event or serious adverse event including one death attributed to treatment-related kidney injury., Conclusion: Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations.

Purpose: CancerLinQ seeks to use data sharing technology to improve quality of care, improve health outcomes, and advance evidence-based research. Understanding the experiences and concerns of patients is vital to ensure its trustworthiness and success., Methods: In a survey of 1,200 patients receiving care in four CancerLinQ-participating practices, we evaluated awareness and attitudes regarding participation in data sharing., Results: Of 684 surveys received (response rate 57%), 678 confirmed cancer diagnosis and constituted the analytic sample; 54% were female, and 70% were 60 years and older; 84% were White. Half (52%) were aware of the existence of nationwide databases focused on patients with cancer before the survey. A minority (27%) indicated that their doctors or staff had informed them about such databases, 61% of whom indicated that doctors or staff had explained how to opt out of data sharing. Members of racial/ethnic minority groups were less likely to be comfortable with research (88% v 95%; P = .002) or quality improvement uses (91% v 95%; P = .03) of shared data. Most respondents desired to know how their health information was used (70%), especially those of minority race/ethnicity (78% v 67% of non-Hispanic White respondents; P = .01). Under half (45%) felt that electronic health information was sufficiently protected by current law, and most (74%) favored an official body for data governance and oversight with representation of patients (72%) and physicians (94%). Minority race/ethnicity was associated with increased concern about data sharing (odds ratio [OR], 2.92; P < .001). Women were less concerned about data sharing than men (OR, 0.61; P = .001), and higher trust in oncologist was negatively associated with concern (OR, 0.75; P = .03)., Conclusion: Engaging patients and respecting their perspectives is essential as systems like CancerLinQ evolve.

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with lung cancer and ERBB2 mutation or amplification treated with pertuzumab plus trastuzumab (P + T) are reported., Methods: Eligible patients had advanced lung cancer of any histology, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2 mutation or amplification. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) per RECIST v. 1.1 or stable disease (SD) of at least 16 weeks duration (SD16+). Secondary end points included safety, duration of response, duration of SD, progression-free survival, and overall survival., Results: Twenty-eight patients with lung cancer (27 non-small-cell, 1 small-cell) and ERBB2 mutation (n = 15), ERBB2 amplification (n = 12), or both (n = 1) were enrolled from November 2016 to July 2020. All patients were evaluable for efficacy and toxicity. Three patients with partial response (two ERBB2 mutation; one both mutation and amplification) and seven patients with SD16+ (five ERBB2 mutation; two amplification) were observed for a DC rate of 37% (95% CI, 21 to 50; P = .005) and OR rate of 11% (95% CI, 2 to 28). Five patients had one or more grade 3 or 4 adverse or serious adverse events at least possibly related to P + T., Conclusion: Combination P + T showed evidence of antitumor activity in heavily pretreated patients with non-small-cell lung cancer and ERBB2 mutation or amplification, particularly those with ERBB2 exon 20 insertion mutations.

Purpose: The TAPUR Study is a pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from a cohort of patients with endometrial cancer (EC) with ERBB2 or ERBB3 (ERBB2/3) amplification, overexpression, or mutation treated with pertuzumab plus trastuzumab (P + T) are reported., Methods: Eligible patients had advanced EC, no standard treatment options, measurable disease (RECIST v1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and tumors with ERBB2/3 amplification, overexpression, or mutation. Simon's two-stage design was used with a primary end point of disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks (SD16+) duration. Secondary end points include safety, duration of response, duration of SD, progression-free survival (PFS), and overall survival (OS)., Results: Twenty-eight patients were enrolled from March 2017 to November 2019; all patients were evaluable for efficacy and toxicity. Seventeen patients had tumors with ERBB2/3 amplification and/or overexpression, eight with both ERBB2 amplification and ERBB2/3 mutations, and three with only ERBB2 mutations. Ten patients had DC (two partial response and eight SD16+); all 10 had ERBB2 amplification, and 6 of the 10 patients with DC had >1 ERBB2/3 alteration. DC and OR rates were 37% (95% CI, 21 to 50) and 7% (95% CI, 1 to 24), respectively; the median PFS and median OS were 16 weeks (95% CI, 10-28) and 61 weeks (95% CI, 24-105), respectively. One patient experienced a grade 3 serious adverse event (muscle weakness) at least possibly related to P + T., Conclusion: P + T has antitumor activity in heavily pretreated patients with EC with ERBB2 amplification and warrants additional study.

Background: The current model of clinical drug development in oncology displays major limitations due to a high attrition rate in patient enrollment in early phase trials and a high failure rate of drugs in phase III studies., Objective: Integrating transcriptomics for selection of patients has the potential to achieve enhanced speed and efficacy of precision oncology trials for any targeted therapies or immunotherapies., Methods: Relative gene expression level in the metastasis and normal organ-matched tissues from the WINTHER database was used to estimate in silico the potential clinical benefit of specific treatments in a variety of metastatic solid tumors., Results: As example, high mRNA expression in tumor tissue compared to analogous normal tissue of c-MET and its ligand HGF correlated in silico with shorter overall survival (OS; p  < 0.0001) and may constitute an independent prognostic marker for outcome of patients with metastatic solid tumors, suggesting a strategy to identify patients most likely to benefit from MET-targeted treatments. The prognostic value of gene expression of several immune therapy targets (PD-L1, CTLA4, TIM3, TIGIT, LAG3, TLR4) was investigated in non-small-cell lung cancers and colorectal cancers (CRCs) and may be useful to optimize the development of their inhibitors, and opening new avenues such as use of anti-TLR4 in treatment of patients with metastatic CRC., Conclusion: This in silico approach is expected to dramatically decrease the attrition of patient enrollment and to simultaneously increase the speed and detection of early signs of efficacy. The model may significantly contribute to lower toxicities. Altogether, our model aims to overcome the limits of current approaches., Competing Interests: − Dr. Vladimir Lazar, Catherine Bresson, and Fanny Wunder are full-time employees of Worldwide Innovative Network (WIN) Association – WIN Consortium. − Shai Magidi receives consultancy fees from Worldwide Innovative Network (WIN) Association – WIN Consortium. − Worldwide Innovative Network (WIN) Association – WIN Consortium is the owner of the patent family entitled Digital Display. The inventors are Dr. Vladimir Lazar and Shai Magidi. − Dr. Baolin Zhang disclaimer: The views expressed in this manuscript are those of the author and do not represent the views or policies of the U.S. FDA. − Pr. Christophe Le Tourneau has participated in advisory boards from Celgene, AstraZeneca, MSD, BMS, Merck Serono, Nanobiotix, Rakuten, Seatlle Genetics, and Roche. − Pr. Eric Raymond : SCOR Health Science – consulting and shareholder; GenoScience Pharma – consulting and shareholder, Axoltis – shareholder, Stromacare – consulting and shareholderInstitut des Vaisseaux et du Sang (IVS) – Scientific Director, Institut National du Cancer (INCa France) – Member of the Board of Directors. − Pr. Michel Ducreux reports consulting or advisory role: Amgen, AstraZeneca, Bayer, Daiichi Sankyo, Merck Serono, MSD, Pierre Fabre, Roche, Servier. Speakers’ bureau: AstraZeneca, Bayer, Roche, Terumo Amir Onn receives consulting fees from: Roche Israel, MSD Israel, Boehringer Ingelheim, and AstraZeneca. − Enriqueta Felip reports consulting or advisory role: Abbvie, Amgen, AstraZeneca, Bayer, Blue Print Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, Merck, MSD, Novartis, Pfizer, Puma Biotechnology, Roche, Sanofi Genzyme, Takeda; Speakers’ bureau or expert testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Medscape, MSD, Novartis, Peervoice, Pfizer, Prime Oncology, Roche, Springer, Takeda, Touchime, CME Outfitters; Research grant or funding: Grant for Oncology Innovation (GOI), Fundación Merck Salud; Other: Grífols (independent member of the board). − Dr. Josep Tabernero declares scientific consultancy role for Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Partners, Novartis, Peptomyc, Pfizer, Pharmacyclics, ProteoDesign SL, Rafael Pharmaceuticals, F. Hoffmann-La Roche Ltd, Sanofi, SeaGen, Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. − Gerald Batist collaborates in formal clinical trial contracts, IITs and in joint grants funded by Canadian and Quebec governments with Roche, Merck, Novartis, AstraZeneca, Bayer, Esperas, Aurka, Caprion, MRM. − Razelle Kurzrock is Chief Medical Officer of the Worldwide Innovative Network (WIN) Association – WIN Consortium. She has received research funding from Genentech, Merck Serono, Pfizer, Boehringer Ingelheim, TopAlliance, Takeda, Incyte, Debiopharm, Medimmune, Sequenom, Foundation Medicine, Konica Minolta, Grifols, Omniseq, and Guardant, as well as consultant and/or speaker fees and/or advisory board for X-Biotech, Neomed, Pfizer, Actuate Therapeutics, Roche, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics, Inc., has an equity interest in IDbyDNA and CureMatch Inc, serves on the Board of CureMatch and CureMetrix, and is a co-founder of CureMatch. − Richard L. Schilsky is the Chairman of Worldwide Innovative Network (WIN) Association – WIN Consortium. He declares Research Support: continues to serve as the PI of the ASCO TAPUR trial. ASCO receives research grants from the following companies in support of this trial: AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Genentech, Lilly, Merck, Pfizer, Seagen. He does not personally receive any compensation from these companies; receives Consulting: he is consultant to the following companies: Brylogyx, Cellworks*, Clarified Precision Medicine*, EQRx*, Illumina*, Scandion Oncology* and receive compensation from those designated (*). − Dr. Baolin Zhang, Dr. Jacques Raynaud and Pr. Eitan Rubin, declare no potential conflicts of interest., (© The Author(s), 2023.)

Purpose: The TAPUR Study is a phase II basket trial that aims to evaluate activity of approved targeted agents in patients with advanced cancers with potentially actionable genomic variants. Data from a cohort of patients with metastatic castrate-resistant prostate cancer (mCRPC) and BRCA1 / 2 mutations treated with olaparib are reported., Methods: Eligible patients with measurable mCRPC were matched to treatment according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary end point of disease control, defined as objective response or stable disease of at least 16-week duration. Secondary end points include radiographic progression-free survival, overall survival, duration of response, duration of stable disease, and safety., Results: Thirty patients with mCRPC with BRCA1 / 2 mutations were treated with olaparib. The disease control rate was 69% (95% CI, 51 to 81), and the objective response rate was 58% (95% CI, 37 to 77). The median radiographic progression-free survival and the median overall survival were 38.4 (95% CI, 16.3 to 52.1) weeks and 76.4 (95% CI, 49.3 to 106.0) weeks, respectively. Six of 30 (20%) patients experienced grade 3-4 adverse or serious adverse events including anemia, aspiration, decreased WBC count, and fatigue., Conclusion: Olaparib has antitumor activity in patients with mCRPC with BRCA1 / 2 mutations and warrants further study to determine how to best integrate it into the standard treatment of patients with BRCA1 / 2 -mutated prostate cancer.

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.

Background: SARS-CoV-2 (COVID-19) elicits a T-cell antigen-mediated immune response of variable efficacy. To understand this variability, we explored transcriptomic expression of angiotensin-converting enzyme 2 ( ACE2 , the SARS-CoV-2 receptor) and of immunoregulatory genes in normal lung tissues from patients with non-small cell lung cancer (NSCLC)., Methods: This study used the transcriptomic and the clinical data for NSCLC patients generated during the CHEMORES study [ n  = 123 primary resected (early-stage) NSCLC] and the WINTHER clinical trial ( n  = 32 metastatic NSCLC)., Results: We identified patient subgroups with high and low ACE2 expression ( p  = 1.55 × 10 -19 ) in normal lung tissue, presumed to be at higher and lower risk, respectively, of developing severe COVID-19 should they become infected. ACE2 transcript expression in normal lung tissues (but not in tumor tissue) of patients with NSCLC was higher in individuals with more advanced disease. High- ACE2 expressors had significantly higher levels of CD8+ cytotoxic T lymphocytes and natural killer cells but with presumably impaired function by high Thymocyte Selection-Associated High Mobility Group Box Protein TOX ( TOX ) expression. In addition, immune checkpoint-related molecules - PD-L1, CTLA-4, PD-1 , and TIGIT - are more highly expressed in normal (but not tumor) lung tissues; these molecules might dampen immune response to either viruses or cancer. Importantly, however, high inducible T-cell co-stimulator ( ICOS ), which can amplify immune and cytokine reactivity, significantly correlated with high ACE2 expression in univariable analysis of normal lung (but not lung tumor tissue)., Conclusions: We report a normal lung immune-tolerant state that may explain a potential comorbidity risk between two diseases - NSCLC and susceptibility to COVID-19 pneumonia. Further, a NSCLC patient subgroup has normal lung tissue expressing high ACE2 and high ICOS transcripts, the latter potentially promoting a hyperimmune response, and possibly leading to severe COVID-19 pulmonary compromise., (© The Author(s), 2022.)

Purpose: The TAPUR Study is a pragmatic phase II basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from two cohorts of patients with colorectal cancer (CRC) with either ERBB2 amplifications or ERBB2 or ERBB3 (ERBB2/3) mutations treated with pertuzumab plus trastuzumab (P + T) are reported., Methods: Eligible patients with measurable CRC were selected for treatment with P + T according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary study end point of disease control (DC; objective response [OR] or stable disease of at least 16 weeks duration [SD16+]). Secondary end points include safety, response duration, progression-free survival (PFS), and overall survival (OS)., Results: Thirty-eight patients with CRC with ERBB2 amplification (N = 28) or ERBB2 / 3 mutations (N = 10) were treated with P + T. For the ERBB2 amplification cohort, DC and OR were observed in 54% and 25% of patients, respectively; the median PFS and median OS (95% CIs) were 17.2 (11.1 to 27.4) weeks and 60.0 (32.1 to 102.3) weeks, respectively. For the ERBB2 / 3 mutation cohort, DC and OR were observed in 10% and 0% of patients, respectively; the median PFS and median OS were 9.6 (5.1 to 16.0) weeks and 28.8 (7.6 to 146.3) weeks, respectively. Four of 38 patients experienced grade 3 adverse events or serious adverse events including anemia, infusion reaction, diarrhea, left ventricular systolic dysfunction, and decreased lymphocyte count., Conclusion: Although P + T treatment does not appear to have antitumor activity in CRC with ERBB2/3 mutations, this combination has antitumor activity in patients with CRC with ERBB2 amplification and warrants further study.

Purpose: The prognosis of patients with non-small-cell lung cancer (NSCLC), traditionally determined by anatomic histology and TNM staging, neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying patients with NSCLC at increased risk of recurrence after curative-intent surgery remains an important unmet need so that known effective adjuvant treatments can be offered to those at highest risk of recurrence., Methods: Relative gene expression level in the primary tumor and normal bronchial tissues was used to retrospectively assess their association with disease-free survival (DFS) in a cohort of 120 patients with NSCLC who underwent curative-intent surgery., Results: Low versus high Digital Display Precision Predictor (DDPP) score (a measure of relative gene expression) was significantly associated with shorter DFS (highest recurrence risk; P = .006) in all patients and in patients with TNM stages 1-2 ( P = .00051; n = 83). For patients with stages 1-2 and low DDPP score (n = 29), adjuvant chemotherapy was associated with improved DFS ( P = .0041). High co-overexpression of CTLA-4 , PD-L1 , and ICOS in normal lung (28 of 120 patients) was also significantly associated with decreased DFS ( P = .0013), suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS ( P = 2.12E-11)., Conclusion: TNM stage, DDPP score, and immune competence status of normal lung are independent prognostic factors in multivariate analysis. Our findings open new avenues for prospective prognostic assessment and treatment assignment on the basis of transcriptomic profiling of tumor and normal lung tissue in patients with NSCLC., Competing Interests: Vladimir LazarPatents, Royalties, Other Intellectual Property: I am inventor on patentes filed by WIN Consortium I do not receive money Nicolas GirardEmployment: AstraZeneca (I)Consulting or Advisory Role: Roche, Lilly, AstraZeneca, Novartis, Pfizer, Bristol Myers Squibb, MSD, Takeda, Janssen, Sanofi, AmgenResearch Funding: Roche (Inst), AstraZeneca (Inst), BMS (Inst)Travel, Accommodations, Expenses: Roche Eric RaymondEmployment: Genoscience Pharma, SCOR, StromaCare, Onward TherapeuticsLeadership: AFR-OncologyStock and Other Ownership Interests: Neuronax, Oncoethix, Genoscience Pharma, SCORConsulting or Advisory Role: Lilly, Pfizer, Merck Serono, PharmaEngine, Novartis/lpsen, Celgene Jean-François MartiniEmployment: PfizerStock and Other Ownership Interests: Pfizer Susan GalbraithEmployment: AstraZenecaLeadership: BB Biotech VenturesStock and Other Ownership Interests: AstraZeneca Benjamin SolomonConsulting or Advisory Role: BayerResearch Funding: AstraZeneca/Merck (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/358846 Hovav NechushtanResearch Funding: AstraZeneca (Inst), Spectrum Pharmaceuticals (Inst), Lilly (Inst), Merck KGaA (Inst)Uncompensated Relationships: MSD Amir OnnHonoraria: Boehringer Ingelheim, Roche, MSD, AmgenConsulting or Advisory Role: Boehringer Ingelheim, MSDSpeakers' Bureau: AstraZeneca Raanan BergerStock and Other Ownership Interests: BelongHonoraria: Bristol Myers Squibb, Roche Israel, AstraZeneca, Pfizer, MSDConsulting or Advisory Role: Belong, MSD Oncology, BMSSpeakers' Bureau: Mitra Biotech, BMS, MSD OncologyTravel, Accommodations, Expenses: Mitra Biotech, Bristol Myers Squibb, MSD, AstraZeneca Sadakatsu IkedaHonoraria: Chugai Pharma, Novartis, AstraZeneca, Taiho Pharmaceutical, Guardant Health, Bristol Myers Squibb-Ono Pharmaceutical, MSD, ACT Genomics, Roche, Canon Medical System, ACT MedConsulting or Advisory Role: Genodive Pharma (Inst)Research Funding: ACT Genomics (Inst), Hitachi (Inst), Canon Medical System (Inst) Ulrik LassenHonoraria: Bayer, Pfizer, NovartisConsulting or Advisory Role: Bayer, PfizerResearch Funding: BMS (Inst), Roche (Inst), Pfizer (Inst), GlaxoSmithKline (Inst), Incyte (Inst), Lilly (Inst) Enriqueta FelipConsulting or Advisory Role: Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Lilly, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Pfizer, Sanofi, Takeda, Peptomyc, Daiichi Sankyo Europe GmbH, F. Hoffmann La Roche, Merck Sharp & DohmeSpeakers’ Bureau: AstraZeneca, Bristol Myers Squibb, Lilly, Medscape, Merck Sharp & Dohme, PeerVoice, Pfizer, Takeda, Amgen, F. Hoffmann La Roche, Janssen, Medical Trends, Merck Serono, Sanofi, TouchONCOLOGYResearch Funding: Merck (Inst), Merck KGaA (Inst)Other Relationship: GRiFOLS Josep TaberneroStock and Other Ownership Interests: Oniria TherapeuticsConsulting or Advisory Role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Sanofi, Taiho Pharmaceutical, Peptomyc, Chugai Pharma, Pfizer, Seattle Genetics, Array BioPharma, AstraZeneca, Genentech, Menarini, Servier, HalioDx, F. Hoffmann La Roche, Mirati Therapeutics, Pierre Fabre, Tessa Therapeutics, TheraMyc, Daiichi Sankyo, Samsung Bioepis, IQvia, Ikena Oncology, Merus, Neophore, Orion Biotechnology, Hutchison MediPharma, Scandion Oncology, Ona Therapeutics, Sotio, Inspirna, Scorpion TherapeuticsOther Relationship: Imedex, Medscape, MJH Life Sciences, Peerview, Physicans' Education Resource Alan SpatzConsulting or Advisory Role: Janssen, Bristol Myers Squibb, Pfizer/EMD Serono, Merck, Roche, AstraZeneca, Novartis, Bayer, AbbVieResearch Funding: Merck (Inst), Bristol Myers Squibb (Inst) C.S. PrameshStock and Other Ownership Interests: Aurobindo Philippe GirardHonoraria: Bayer, LEO Pharma, BMS/PfizerConsulting or Advisory Role: LEO Pharma, Bayer, BMS/PfizerTravel, Accommodations, Expenses: Bayer, LEO Pharma, BMS/Pfizer Jean-Yves BlayLeadership: Innate PharmaHonoraria: Roche, AstraZeneca, PharmaMar, MSD, BMS, Bayer, Ignyta, DecipheraConsulting or Advisory Role: Roche, Pharmamar, Deciphera, Blueprint Medicines, Bayer, Karyopharm TherapeuticsResearch Funding: GlaxoSmithKline (Inst), Pharmamar (Inst), Novartis (Inst), Bayer (Inst), Roche (Inst), BMS (Inst), MSD (Inst), Deciphera (Inst), AstraZeneca (Inst), OSE Pharma (Inst)Travel, Accommodations, Expenses: Roche Angel PorgadorStock and Other Ownership Interests: PooldiConsulting or Advisory Role: PiNKPatents, Royalties, Other Intellectual Property: Ben-Gurion University, Israel, several patents Eitan RubinStock and Other Ownership Interests: Pfizer Razelle KurzrockLeadership: CureMatch, CureMetrixStock and Other Ownership Interests: CureMatch, IDbyDNA, CureMetrixHonoraria: Roche, EUSA Pharma, NeoGenomics Laboratories, Biocom, NeoMed, Advanced Therapeutics, LEK, AACR, Chugai Pharma USA, Wiley, Merck, Pfizer, Meyer Consulting, Foundation Medicine, Turning Point Therapeutics, Bicara TherapeuticsConsulting or Advisory Role: Actuate Therapeutics, Loxo, XBiotech, NeoMed, Roche, Gaido, Soluventis, Pfizer, Merck, Turning Point Therapeutics, TD2/Volastra, Bicara Therapeutics, AstraZeneca, Biological Dynamics, Daiichi Sankyo, Eisai, EOM Pharmaceuticals, lylon, ProsperdtxSpeakers' Bureau: RocheResearch Funding: Guardant Health (Inst), Sequenom (Inst), Merck Serono (Inst), Genentech (Inst), Pfizer (Inst), Foundation Medicine (Inst), Incyte (Inst), Konica Minolta (Inst), Grifols (Inst), OmniSeq (Inst), Debiopharm Group (Inst), Boehringer Ingelheim (Inst), Top Alliance BioScience (Inst), Takeda (Isnt), Medlmmune (Inst), Biological Dynamics (Inst)Travel, Accommodations, Expenses: Roche, EUSA Pharma, NeoGenomics Laboratories, Biocom, NeoMed, Advanced Therapeutics, LEK, AACR, Chugai Pharma USA, Wiley Richard L. SchilskyLeadership: Clarified Precision MedicineStock and Other Ownership Interests: EQRxConsulting or Advisory Role: Cellworks, Scandion Oncology, Bryologyx, IIIumina, EQRx, Syapse, ZephyrAIResearch Funding: AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Lilly (Inst), Merck (Inst), Pfizer (Inst), Boehringer Ingelheim (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/I138818/summaryNo other potential conflicts of interest were reported.

Background: The Worldwide Innovative Network (WIN) Consortium has developed the Simplified Interventional Mapping System (SIMS) to better define the cancer molecular milieu based on genomics/transcriptomics from tumor and analogous normal tissue biopsies. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced non-small cell lung cancer (NSCLC)., Methods: Patients with advanced NSCLC (no EGFR, ALK, or ROS1 alterations; PD-L1 unrestricted; ≤2 prior therapy lines) received avelumab, axitinib, and palbociclib (3 + 3 dose escalation design)., Results: Fifteen patients were treated (five centers, four countries): six at each of dose levels 1 (DL1) and DL2; three at DL3. The most common ≥Grade 3 adverse events were neutropenia, hypertension, and fatigue. The recommended Phase II dose (RP2D) was DL1: avelumab 10 mg/kg IV q2weeks, axitinib 3 mg po bid, and palbociclib 75 mg po daily (7 days off/21 days on). Four patients (27%) achieved a partial response (PR) (progression-free survival [PFS]: 14, 24, 25 and 144+ weeks), including two after progression on pembrolizumab. Four patients attained stable disease (SD) that lasted ≥24 weeks: 24, 27, 29, and 64 weeks. At DL1 (RP2D), four of six patients (66%) achieved stable disease (SD) ≥6 months/PR (2 each). Responders included patients with no detectable PD-L1 expression and low tumor mutational burden., Conclusions: Overall, eight of 15 patients (53%) achieved clinical benefit (SD ≥ 24 weeks/PR) on the avelumab, axitinib, and palbociclib combination. This triplet showed antitumor activity in NSCLC, including in tumors post-pembrolizumab progression, and was active at the RP2D, which was well tolerated. NCT03386929 clinicaltrial.gov., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: People with cancer are at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ASCO's COVID-19 registry promotes systematic data collection across US oncology practices., Methods: Participating practices enter data on patients with SARS-CoV-2 infection in cancer treatment. In this analysis, we focus on all patients with hematologic or regional or metastatic solid tumor malignancies. Primary outcomes are 30- and 90-day mortality rates and change over time., Results: Thirty-eight practices provided data for 453 patients from April to October 2020. Sixty-two percent had regional or metastatic solid tumors. Median age was 64 years. Forty-three percent were current or previous cigarette users. Patients with B-cell malignancies age 61-70 years had twice mortality risk (hazard ratio = 2.1 [95% CI, 1.3 to 3.3]) and those age > 70 years had 4.5 times mortality risk (95% CI, 1.8 to 11.1) compared with patients age ≤ 60 years. Association between survival and age was not significant in patients with metastatic solid tumors ( P = .12). Tobacco users had 30-day mortality estimate of 21% compared with 11% for never users (log-rank P = .005). Patients diagnosed with SARS-CoV-2 before June 2020 had 30-day mortality rate of 20% (95% CI, 14% to 25%) compared with 13% (8% to 18%) for those diagnosed in or after June 2020 ( P = .08). The 90-day mortality rate for pre-June patients was 28% (21% to 34%) compared with 21% (13% to 28%; P = .20)., Conclusion: Older patients with B-cell malignancies were at increased risk for death (unlike older patients with metastatic solid tumors), as were all patients with cancer who smoke tobacco. Diagnosis of SARS-CoV-2 later in 2020 was associated with more favorable 30- and 90-day mortality, likely related to more asymptomatic cases and improved clinical management., Competing Interests: Kathryn F. MilehamHonoraria: Bristol Myers Squibb, RegeneronConsulting or Advisory Role: AstraZeneca, Bayer, Merck Charu AggarwalConsulting or Advisory Role: Genentech, Lilly, Celgene, Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/Astra ZenecaSpeakers' Bureau: AstraZeneca (I), Roche/Genentech (I)Research Funding: Genentech/Roche (Inst), Incyte (Inst), Macrogenics (Inst), Merck Sharp & Dohme (Inst), AstraZeneca/MedImmune (Inst) Daniel J. MesenhowskiEmployment: Virginia Cancer Specialists Alexander SpiraLeadership: NEXT Oncology Virginia (Inst)Stock and Other Ownership Interest: LillyHonoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, BayerConsulting or Advisory Role: Array BioPharma (Inst), Incyte, Amgen, Novartis, AstraZeneca/MedImmune (Inst), Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Merck (Inst), Bristol Myers Squibb (Inst), Takeda, Janssen Research & DevelopmentResearch Funding: Roche (Inst), AstraZeneca (Inst), Boehringer Ingelheim (Inst), Astellas Pharma (Inst), MedImmune (Inst), Novartis (Inst), Newlink Genetics (Inst), Incyte (Inst), AbbVie (Inst), Ignyta (Inst), LAM Therapeutics (Inst), Trovagene (Inst), Takeda (Inst), Macrogenics (Inst), CytomX Therapeutics (Inst), Astex Pharmaceuticals (Inst), Bristol-Myers Squibb (Inst), Loxo (Inst), Arch Therapeutics (Inst), Gritstone Oncology (Inst), Plexxikon (Inst), Amgen (Inst), Daiichi Sankyo (Inst), ADC Therapeutics (Inst), Janssen Oncology (Inst), Mirati Therapeutics (Inst), Rubius Therapeutics (Inst) Eric J. ClaytonEmployment: US Oncology, HCA HealthcareStock and Other Ownership Interests: HCA HealthcareResearch Funding: US OncologyTravel, Accommodations, Expenses: US Oncology David WaterhouseConsulting or Advisory Role: Bristol Myers Squibb, AZTherapies, AbbVie, Amgen, McGivney Global Advisors, Janssen Oncology, Seattle Genetics, Jazz Pharmaceuticals, Exelixis, Eisai, EMD Serono, Merck, Pfizer, Mirati Therapeutics, Regeneron/SanofiSpeakers' Bureau: Bristol-Myers Squibb, Janssen Oncology, Merck, AstraZeneca, Amgen, EMD SeronoTravel, Accommodations, Expenses: Bristol Myers Squibb Abdul-Rahman JaziehStock and Other Ownership Interests: Innovative Healthcare InstituteResearch Funding: MSD Oncology, AstraZeneca, PfizerTravel, Accommodations, Expenses: Bristol Myers SquibbOther Relationship: MSD (Inst) Ronald C. ChenConsulting or Advisory Role: Medivation/Astellas, Accuray, Bayer, Blue Earth Diagnostics, AbbVie, Myovant Sciences, Genentech, PfizerResearch Funding: Accuray Julie R. GralowConsulting or Advisory Role: Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, Genomic Health Richard L. SchilskyLeadership: ClariifiConsulting or Advisory Role: Cellworks, Scandion Oncology, BryologyxResearch Funding: AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Lilly (Inst), Merck (Inst), Pfizer (Inst), Boehringer Ingelheim (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/1138818/summary Elizabeth Garrett-MayerConsulting or Advisory Role: DecipheraNo other potential conflicts of interest were reported.

Purpose: The increased number and expanded utilization of biosimilars raise important considerations for their safe and appropriate use in oncology practice. This report provides an update on currently approved oncology biosimilars and identifies current knowledge gaps in the management of patients with cancer., Methods: An Expert Panel was convened to review the medical literature and to provide a practical summary of currently approved biosimilar therapeutics for cancer treatment or supportive care in the United States., Results: A total of 17 cancer or cancer-related biosimilar products have been approved by the US Food and Drug Administration since 2015. Despite years of clinical experience with oncology biosimilars, variance in their use persists. ASCO supports that biosimilars and reference products are considered equally efficacious for the purpose of inclusion in ASCO clinical practice guideline recommendations., Conclusion: The use of biosimilars might provide competitive, lower-cost alternatives to biologics used in cancer care, and specific mention in ASCO guidelines and other evidence products is supported where appropriate., Competing Interests: Gary H. LymanConsulting or Advisory Role: G1 Therapeutics, Samsung Bioepis, BeyondSpring Pharmaceuticals, Sandoz, Jazz Pharmaceuticals, Partner Therapeutics, E.R. Squibb Sons, LLC, MSD, Seattle Genetics, Kallyope, TEVA, Spectrum Pharmaceuticals, Frensenius KabiResearch Funding: Amgen (Inst) Richard L. SchilskyLeadership: Clarified Precision MedicineConsulting or Advisory Role: Cellworks, Scandion Oncology, Bryologyx, Illumina, EQRxResearch Funding: AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Lilly (Inst), Merck (Inst), Pfizer (Inst), Boehringer Ingelheim (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/1138818/summary Douglas E. PetersonStock and Other Ownership Interests: Allergan (I), Celgene (I), Gilead Sciences (I), Procter & Gamble (I), Roche (I), Bristol Myers Squibb (I), Johnson & Johnson (I)Honoraria: PierianDxConsulting or Advisory Role: Amgen, PSI Pharma Support America, Applied Glycan-Oral Health, AEC Partners, BrainCool, Medicxi Ventures (UK) LLP, Boston MedTech Advisors Scott T. TagawaConsulting or Advisory Role: Medivation, Astellas Pharma, Dendreon, Janssen, Genentech, Endocyte, Immunomedics, Karyopharm Therapeutics, AbbVie, Tolmar, QED Therapeutics, Amgen, Sanofi, Pfizer, Clovis Oncology, Novartis, Genomic Health, POINT Biopharma, Blue Earth Diagnostics, Seattle Genetics, AIkido Pharma, 4D Pharma, Clarity Pharmaceuticals, Gilead Sciences, Telix Pharmaceuticals, Bayer, Myovant Sciences, Convergent TherapeuticsResearch Funding: Lilly (Inst), Sanofi (Inst), Janssen (Inst), Astellas Pharma (Inst), Progenics (Inst), Millennium (Inst), Amgen (Inst), Bristol Myers Squibb (Inst), Dendreon (Inst), Rexahn Pharmaceuticals (Inst), Bayer (Inst), Genentech (Inst), Newlink Genetics (Inst), Inovio Pharmaceuticals (Inst), AstraZeneca (Inst), Immunomedics (Inst), Novartis (Inst), AVEO (Inst), Boehringer Ingelheim (Inst), Merck (Inst), Stem CentRx (Inst), Karyopharm Therapeutics (Inst), AbbVie (Inst), Medivation (Inst), Endocyte (Inst), Exelixis (Inst), Clovis Oncology (Inst), POINT Biopharma (Inst)Patents, Royalties, Other Intellectual Property: Patent Royalty from Immunomedics/GileadTravel, Accommodations, Expenses: Sanofi, Immunomedics, AmgenUncompensated Relationships: ATLAB Pharma, Phosplatin Therapeutics Mariana Chavez-MacGregorEmployment: MD Anderson Physicians NetworkHonoraria: Pfizer, EisaiConsulting or Advisory Role: Roche/Genentech, AstraZeneca, Novartis, Pfizer, asofar, Genomic Health, Exact Sciences, AstraZeneca/Daiichi SankyoResearch Funding: Novartis (Inst)Expert Testimony: Abbott Laboratories, PfizerTravel, Accommodations, Expenses: PfizerOther Relationship: RocheUncompensated Relationships: Legacy Healthcare Services, The Hope FoundationNo other potential conflicts of interest were reported.

Purpose: Scholars have examined patients' attitudes toward secondary use of routinely collected clinical data for research and quality improvement. Evidence suggests that trust in health care organizations and physicians is critical. Less is known about experiences that shape trust and how they influence data sharing preferences., Materials and Methods: To explore learning health care system (LHS) ethics, democratic deliberations were hosted from June 2017 to May 2018. A total of 217 patients with cancer participated in facilitated group discussion. Transcripts were coded independently. Finalized codes were organized into themes using interpretive description and thematic analysis. Two previous analyses reported on patient preferences for consent and data use; this final analysis focuses on the influence of personal lived experiences of the health care system, including interactions with providers and insurers, on trust and preferences for data sharing., Results: Qualitative analysis identified four domains of patients' lived experiences raised in the context of the policy discussions: (1) the quality of care received, (2) the impact of health care costs, (3) the transparency and communication displayed by a provider or an insurer to the patient, and (4) the extent to which care coordination was hindered or facilitated by the interchange between a provider and an insurer. Patients discussed their trust in health care decision makers and their opinions about LHS data sharing., Conclusion: Additional resources, infrastructure, regulations, and practice innovations are needed to improve patients' experiences with and trust in the health care system. Those who seek to build LHSs may also need to consider improvement in other aspects of care delivery., Competing Interests: Angela R. BradburyConsulting or Advisory Role: MerckResearch Funding: AstraZeneca/Merck (Inst) Robin ZonStock and Other Ownership Interests: AC3, CytoSorbents, Moderna Therapeutics, Oncolytics Biotech, TG Therapeutics, Select Sector SPDR Health CareConsulting or Advisory Role: New Century Health, Xentigen Richard L. SchilskyLeadership: Clarified Precision MedicineConsulting or Advisory Role: Cellworks, Scandion Oncology, BryoLogyx, Illumina, EQRxResearch Funding: AstraZeneca (Inst), Bayer (Inst), Bristol Myers Squibb (Inst), Genentech/Roche (Inst), Lilly (Inst), Merck (Inst), Pfizer (Inst), Boehringer Ingelheim (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/1138818/summary Reshma JagsiStock and Other Ownership Interests: Equity QuotientResearch Funding: Genentech (Inst)Expert Testimony: Baptist Health/Dressman Benzinger Lavelle Law, Kleinbard LLC, Sherinian and HassoTravel, Accommodations, Expenses: AmgenOther Relationship: JAMA OncologyOpen Payments Link: https://openpaymentsdata.cms.gov/physician/373670/summaryNo other potential conflicts of interest were reported.

Purpose: The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported., Methods: Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety., Results: Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label., Conclusion: Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options., Competing Interests: Ajjai S. AlvaConsulting or Advisory Role: AstraZeneca, Merck, Pfizer, Bristol Myers SquibbResearch Funding: Genentech, Bristol-Myers Squibb, Merck Sharp & Dohme, Prometheus, Mirati Therapeutics, AstraZeneca, Roche, Bayer, Progenics, Astellas Pharma, Arcus Biosciences, Harpoon Therapeutics, Progenics, Celgene, JanssenTravel, Accommodations, Expenses: Merck, Bristol Myers Squibb Elizabeth Garrett-MayerConsulting or Advisory Role: Deciphera, TYME Susan HalabiEmployment: ASCOConsulting or Advisory Role: Eisai, Ferring Pharmaceuticals Damien HansraEmployment: Cancer Treament Centers of America, Hansra Health Corporation Eugene R. AhnEmployment: Cancer Treament Centers of AmericaLeadership: Cancer Treament Centers of America Timothy L. CannonConsulting or Advisory Role: Loxo, NavicanOther Relationship: Navican/Intermountain Healthcare Pamela CrilleyEmployment: Cancer Treament Centers of AmericaLeadership: Cancer Treament Centers of AmericaTravel, Accommodations, Expenses: Cancer Treament Centers of America Richard L. SchilskyResearch Funding: AstraZeneca, Bayer, Bristol-Myers Squibb, Genentech/Roche, Lilly, Merck, Pfizer, Boehringer IngelheimOpen Payments Link: https://openpaymentsdata.cms.gov/physician/1138818/summaryNo other potential conflicts of interest were reported.

The availability of advanced omics technologies has largely driven development of precision cancer medicine in the United States, but integration in routine cancer care has been challenging. Here, we consider some parameters that would enable a more coordinated, integrated, efficient, and equitable implementation of precision cancer medicine., (© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Globally, there has been little change in mortality rates from cardiovascular (CV) diseases or cancers over the past two decades (1997-2018). This is especially true for heart failure (HF) where 5-year mortality rates remain as high as 45-55%. In the same timeframe, the proportion of drug revenue, and regulatory drug approvals for cancer drugs, far out paces those for CV drugs. In 2018, while cancer drugs made 27% of Food and Drug Administration drug approvals, only 1% of drug approvals was for a CV drug, and over this entire 20 year span, only four drugs were approved for HF in the USA. Cardiovascular trialists need to reassess the design, execution, and purpose of CV clinical trials. In the area of oncology research, trials are much smaller, follow-up is shorter, and targeted therapies are common. Cardiovascular diseases and cancer are the two most common causes of death globally, and although they differ substantially, this review evaluates whether some elements of oncology research may be applicable in the CV arena. As one of the most underserved CV diseases, the review focuses on aspects of cancer research that may be applicable to HF research with the aim of streamlining the clinical trial process and decreasing the time and cost required to bring safe, effective, treatments to patients who need them. The paper is based on discussions among clinical trialists, industry representatives, regulatory authorities, and patients, which took place at the Cardiovascular Clinical Trialists Workshop in Washington, DC, on 8 December 2019 (https://www.globalcvctforum.com/2019 (14 September 2020))., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Purpose: Cancer clinical trials often accrue slowly or miss enrollment targets. Strict eligibility criteria are a major reason. Restrictive criteria also limit opportunities for patient participation while compromising external validity of trial results. We examined the impact of broadening select eligibility criteria on characteristics and number of patients eligible for trials, using recommendations of the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research., Experimental Design: A retrospective, observational analysis used electronic health record data from ASCO's CancerLinQ Discovery database. Study cohort included patients with advanced non-small cell lung cancer treated from 2011 to 2018. Patients were grouped by traditional criteria [no brain metastases, no other malignancies, and creatinine clearance (CrCl) ≥ 60 mL/minute] and broadened criteria (including brain metastases, other malignancies, and CrCl ≥ 30 mL/minute)., Results: The analysis cohort included 10,500 patients. Median age was 68 years, and 73% of patients were White. Most patients had stage IV disease (65%). A total of 5,005 patients (48%) would be excluded from trial participation using the traditional criteria. The broadened criteria, however, would allow 98% of patients (10,346) to be potential participants. Examination of patients included by traditional criteria (5,495) versus those added (4,851) by broadened criteria showed that the number of women, patients aged 75+ years, and those with stage IV cancer was significantly greater using broadened criteria., Conclusions: This analysis of real-world data demonstrated that broadening three common eligibility criteria has the potential to double the eligible patient population and include trial participants who are more representative of those encountered in practice. See related commentary by Giantonio, p. 2369 ., (©2021 American Association for Cancer Research.)

The expanding targeted therapy landscape requires combinatorial biomarkers for patient stratification and treatment selection. This requires simultaneous exploration of multiple genes of relevant networks to account for the complexity of mechanisms that govern drug sensitivity and predict clinical outcomes. We present the algorithm, Digital Display Precision Predictor (DDPP), aiming to identify transcriptomic predictors of treatment outcome. For example, 17 and 13 key genes were derived from the literature by their association with MTOR and angiogenesis pathways, respectively, and their expression in tumor versus normal tissues was associated with the progression-free survival (PFS) of patients treated with everolimus or axitinib (respectively) using DDPP. A specific eight-gene set best correlated with PFS in six patients treated with everolimus: AKT2, TSC1, FKB-12, TSC2, RPTOR, RHEB, PIK3CA, and PIK3CB (r = 0.99, p = 5.67E-05). A two-gene set best correlated with PFS in five patients treated with axitinib: KIT and KITLG (r = 0.99, p = 4.68E-04). Leave-one-out experiments demonstrated significant concordance between observed and DDPP-predicted PFS (r = 0.9, p = 0.015) for patients treated with everolimus. Notwithstanding the small cohort and pending further prospective validation, the prototype of DDPP offers the potential to transform patients' treatment selection with a tumor- and treatment-agnostic predictor of outcomes (duration of PFS).