Category: Statistics

JMIR Res Protoc. 2023 Jan 5;12:e38603. doi: 10.2196/38603.

ABSTRACT

BACKGROUND: Mobile health apps have the potential to motivate people to adopt healthier behavior, but many fail to maintain this behavior over time. However, it has been suggested that long-term adherence can be improved by personalizing the proposed interventions. Based on the literature, we created a conceptual framework for selecting appropriate functionalities according to the user’s profile.

OBJECTIVE: This cross-sectional study aims to investigate if the relationships linking functionalities and profiles proposed in our conceptual framework are confirmed by user preferences.

METHODS: A web-based questionnaire comprising several sections was developed to determine the mobile app functionalities most likely to promote healthier behavior. First, participants completed questionnaires to define the user profile (Big Five Inventory-10, Hexad Scale, and perception of the social norm using dimensions of the Theory of Planned Behavior). Second, participants were asked to select the 5 functionalities they considered to be the most relevant to motivate healthier behavior and to evaluate them on a score ranging from 0 to 100. We will perform logistic regressions with the selected functionalities as dependent variables and with the 3 profile scales as predictors to allow us to understand the effect of the participants’ scores on each of the 3 profile scales on the 5 selected functionalities. In addition, we will perform logistic ordinal regressions with the motivation score of the functionalities chosen as dependent variables and with scores of the 3 profile scales as predictors to determine whether the scores on the different profile scales predict the functionality score.

RESULTS: Data collection was conducted between July and December 2021. Analysis of responses began in January 2022, with the publication of results expected by the end of 2022.

CONCLUSIONS: This study will allow us to validate our conceptual model by defining the preferred functionalities according to user profiles.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/38603.

PMID:36602850 | DOI:10.2196/38603

Am J Respir Crit Care Med. 2023 Jan 5. doi: 10.1164/rccm.202207-1331OC. Online ahead of print.

ABSTRACT

RATIONALE: Idiopathic pulmonary fibrosis is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to non-genetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants genome-wide may contribute to the risk of IPF remains unknown.

OBJECTIVES: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk.

METHODS: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ≤0.01) within genes or regions. We also identified individual variants that are influential within genes and estimated the heritability of IPF based on rare and common variants.

MEASUREMENTS AND MAIN RESULTS: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP-heritability of IPF was estimated to be 32% (s.e. 3%).

CONCLUSIONS: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

PMID:36602845 | DOI:10.1164/rccm.202207-1331OC

J Med Internet Res. 2023 Jan 5;25:e43601. doi: 10.2196/43601.

ABSTRACT

BACKGROUND: Telemedicine has a long history; however, its efficacy has been reported with mixed reviews. Studies have reported a wide range of quality implications when using the telemedicine modality of care.

OBJECTIVE: This study aimed to analyze the effectiveness of telemedicine through 6 domains of quality through an analysis of randomized controlled trials (RCTs) published in the literature published, to date, in 2022.

METHODS: A total of 4 databases were searched using a standard Boolean string. The 882,420 results were reduced to 33 for analysis through filtering and randomization. The systematic literature review was conducted in accordance with the Kruse Protocol and reported in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses; 2020).

RESULTS: The Cohen κ statistic was calculated to show agreement between the reviewers (Cohen κ=0.90, strong). Medical outcomes associated with the telemedicine modality were 100% effective with a weighted average effect size of 0.21 (small effect). Many medical outcomes were positive but not statistically better than treatment as usual. RCTs have reported positive outcomes for physical and mental health, medical engagement, behavior change, increased quality of life, increased self-efficacy, increased social support, and reduced costs. All 6 domains of quality were identified in the RCTs and 4 were identified in 100% of the studies. Telemedicine is highly patient-centered because it meets digital preferences, is convenient, avoids stigma, and enables education at one’s own pace. A few barriers exist to its wide adoption, such as staff training and cost, and it may not be the preferred modality for all.

CONCLUSIONS: The effectiveness of telemedicine is equal to or greater than that of traditional care across a wide spectrum of services studied in this systematic literature review. Providers should feel comfortable offering this modality of care as a standard option to patients where it makes sense to do so. Although barriers exist for wide adoption, the facilitators are all patient facing.

TRIAL REGISTRATION: PROSPERO CRD42022343478; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=343478.

PMID:36602844 | DOI:10.2196/43601

Radiat Res. 2023 Jan 5. doi: 10.1667/RADE-22-00154.1. Online ahead of print.

ABSTRACT

The frequency of stable chromosome aberrations (sCA) in lymphocytes is a recognized radiation biological dosimeter. Its analysis can provide insights into factors that affect individual susceptibility as well as into the adequacy of radiation dose estimates used in studies of atomic bomb survivors. We analyzed the relationship between atomic bomb radiation exposure using the most recent DS02R1 dose estimates and the frequency of sCA as determined by FISH in 1,868 atomic bomb survivors. We investigated factors that may affect the background sCA rate and the shape and magnitude of the dose response. As in previous analyses of sCA in atomic bomb survivors that were based on Giemsa staining methods and used older DS86 dose estimates, the relationship between radiation dose and sCA rate was significant (P < 0.0001) with a linear-quadratic relationship at lower doses that did not persist at higher doses. As before, age at the time of the bombing and type of radiation shielding were significant dose-effect modifiers (P < 0.0001), but in contrast the difference in dose response by city was not so pronounced (P = 0.026) with a city effect not evident at doses below 1.25Gy. Background sCA rate increased with age at the time of examination (P < 0.0001), but neither sex, city, nor smoking was significantly associated with background rate. Based on FISH methods and recent dosimetry, the relationship between radiation dose and sCA frequency is largely consistent with previous findings, although the lesser importance of city as an effect modifier may reflect better dosimetry as well as more reproducible scoring of sCA. The persisting difference in sCA dose response by shielding category points to remaining problems with the accuracy or precision of radiation dose estimates in some A-bomb survivors.

PMID:36602819 | DOI:10.1667/RADE-22-00154.1

JAMA Oncol. 2023 Jan 5. doi: 10.1001/jamaoncol.2022.6278. Online ahead of print.

ABSTRACT

IMPORTANCE: Changes in postsurgical opioid prescribing practices may help reduce chronic opioid use in surgical patients.

OBJECTIVE: To investigate whether postsurgical acute pain across different surgical subspecialties can be managed effectively after hospital discharge with an opioid supply of 3 or fewer days and whether this reduction in prescribed opioids is associated with reduced new, persistent opioid use.

DESIGN, SETTING, AND PARTICIPANTS: In this prospective cohort study with a case-control design, a restrictive opioid prescription protocol (ROPP) specifying an opioid supply of 3 or fewer days after discharge from surgery along with standardized patient education was implemented across all surgical services at a tertiary-care comprehensive cancer center. Participants were all patients who underwent surgery from August 1, 2018, to July 31, 2019.

MAIN OUTCOMES AND MEASURES: Main outcomes were the rate of compliance with the ROPP in each surgical service, the mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use determined via a state-run opioid prescription program. Postsurgical complications were also measured.

RESULTS: A total of 4068 patients (mean [SD] age, 61.0 [13.8] years; 2528 women [62.1%]) were included, with 2017 in the pre-ROPP group (August 1, 2018, to January 31, 2019) and 2051 in the post-ROPP group (February 1, 2019, to July 31, 2019). The rate of compliance with the protocol was 95%. After implementation of the ROPP, mean opioid prescription days decreased from a mean (SD) of 3.9 (4.5) days in the pre-ROPP group to 1.9 (3.6) days in the post-ROPP group (P < .001). The ROPP implementation led to a 45% decrease in prescribed opioids after surgery (mean [SD], 157.22 [338.06] mean morphine milligram equivalents [MME] before ROPP vs 83.54 [395.70] MME after ROPP; P < .001). Patients in the post-ROPP cohort requested fewer refills (367 of 2051 [17.9%] vs 422 of 2017 [20.9%] in the pre-ROPP cohort; P = .02). There was no statistically significant difference in surgical complications. The conversion rate to chronic opioid use decreased following ROPP implementation among both opioid-naive patients with cancer (11.3% [143 of 1267] to 4.5% [118 of 2645]; P < .001) and those without cancer (6.1% [19 of 310] to 2.7% [16 of 600]; P = .02).

CONCLUSIONS AND RELEVANCE: In this cohort study, prescribing an opioid supply of 3 or fewer days to surgical patients after hospital discharge was feasible for most patients, led to a significant decrease in the number of opioids prescribed after surgery, and was associated with a significantly decreased conversion to long-term opioid use without concomitant increases in refill requests or significant compromises in surgical recovery.

PMID:36602807 | DOI:10.1001/jamaoncol.2022.6278

JAMA Netw Open. 2023 Jan 3;6(1):e2244975. doi: 10.1001/jamanetworkopen.2022.44975.

ABSTRACT

IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) causes severe inflammation of multiple organ systems after SARS-CoV-2 infection. During the pandemic, surveillance reporting of MIS-C was voluntary, with likely underreporting. For a rare syndrome like MIS-C, numerous data are needed to explore the disease in greater detail.

OBJECTIVE: To use large all-payer billing data and the new International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Clinical Modification (ICD-10-CM) code for MIS-C to compare outcomes across MIS-C and COVID-19 over all 4057 hospitals in 31 states.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cross-sectional study of all COVID-19 and MIS-C hospitalizations in individuals younger than 21 years from 31 states was conducted, using Agency for Healthcare Research and Quality 2021 Healthcare Cost and Utilization Project data. Analyses were conducted from February 1 to October 20, 2022.

MAIN OUTCOMES AND MEASURES: Fifty complications, adverse medication events, costs, and the Social Vulnerability Index.

RESULTS: There were 4107 individuals with MIS-C (median age, 9 [IQR, 5-13] years; 2443 [59.5%] male; 1384 [38.1%] White) and 23 686 individuals with COVID-19 without MIS-C (median age, 15 [IQR, 5-18] years; 12 878 [54.4%] female; 4605 [44.1%] White), with 1.48 (95% CI, 1.35-1.62) MIS-C hospitalizations per 100 000 children per month, ranging from 0.97 hospitalizations per 100 children for White and 1.99 hospitalizations per 100 children for Black children. Outcomes worsened as the number of organ system dysfunctions increased from 2 to 8 organs. Deaths associated with MIS-C increased from less than 1% to 5.8% (95% CI, 3.3%-8.4%) and from less than 1% to 17.2% (95% CI, 11.7%-22.7%) for COVID-19 (P = .001). Adverse medication events associated with MIS-C increased from 4.9% (95% CI, 3.8%-6.0%) to 17.8% (95% CI, 13.7%-22.0%) and from 1.2% (95% CI, 1.0%-1.3%) to 13.4% (95% CI, 8.4%-18.3%) for COVID-19. The median length of stay for MIS-C increased from 4 (IQR, 2-5) to 8 (IQR, 5-12) days and from 3 (IQR, 2-5) to 16 (IQR, 7-23) days for COVID-19. Median costs for MIS-C increased from $16 225 (IQR, $9244-$26 822) to $53 359 (IQR, $35 920-$86 882) and from $6474 (IQR, $3741-$12 103) to $98 643 (IQR, $30 675-$204 956) for COVID-19. The percentage of MIS-C cases that were in Black children doubled from 16.2% to 31.7% (P = .001) as organ dysfunction increased, remaining unchanged with COVID-19. Hospital stays for MIS-C increased by 1 day (P = .01) for Black patients compared with White patients, with Black patients moving from the bottom to top quartile of socioeconomic vulnerability, with no disparity with COVID-19.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, MIS-C was more common and severe than previously reported, with more racial disparities in outcomes than were seen in patients with COVID-19. The findings of this study suggest that relying on mean outcomes for MIS-C from past studies can be misleading, since outcomes and disparities varied widely with the number of multiorgan dysfunctions.

PMID:36602804 | DOI:10.1001/jamanetworkopen.2022.44975

JAMA Netw Open. 2023 Jan 3;6(1):e2249422. doi: 10.1001/jamanetworkopen.2022.49422.

ABSTRACT

IMPORTANCE: Improved, efficient, and acceptable treatments are needed for combat-related posttraumatic stress disorder (PTSD).

OBJECTIVE: To determine the efficacy of 2 compressed prolonged exposure (PE) therapy outpatient treatments for combat-related PTSD.

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted among military personnel and veterans at 4 sites in Texas from 2017 to 2019. Assessors were blinded to conditions. Data were analyzed from November 2020 to October 2022.

INTERVENTIONS: The interventions were massed-PE, which included 15 therapy sessions of 90 minutes each over 3 weeks, vs intensive outpatient program PE (IOP-PE), which included 15 full-day therapy sessions over 3 weeks with 8 treatment augmentations. The IOP-PE intervention was hypothesized to be superior to massed-PE.

MAIN OUTCOMES AND MEASURES: Coprimary outcomes included the Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-5) (CAPS-5) and the PTSD Checklist for DSM-5 (PCL-5) administered at baseline and posttreatment follow-ups. Measures ranged from 0 to 80, with higher scores indicating greater severity. Diagnostic remission and reliable change were secondary outcomes.

RESULTS: Among 319 military personnel and veterans screened, 234 were randomized (mean [SD] age, 39.20 [7.72] years; 182 [78%] male participants), with 117 participants randomized to IOP-PE and 117 participants randomized to massed-PE. A total of 61 participants (26%) were African American, 58 participants (25%) were Hispanic, and 102 participants (44%) were White; 151 participants (65%) were married. Linear mixed-effects models found that CAPS-5 scores decreased in both treatment groups at the 1-month follow-up (IOP-PE: mean difference, -13.85 [95% CI, -16.47 to -11.23]; P < .001; massed-PE: mean difference, -14.13 [95% CI, -16.63 to -11.62]; P < .001). CAPS-5 change scores differed from 1- to 6-month follow-ups (mean difference, 4.44 [95% CI, 0.89 to 8.01]; P = .02). PTSD symptoms increased in massed-PE participants during follow-up (mean difference, 3.21 [95% CI, 0.65 to 5.77]; P = .01), whereas IOP-PE participants maintained treatment gains (mean difference, 1.23 [95% CI, -3.72 to 1.27]; P = .33). PCL-5 scores decreased in both groups from baseline to 1-month follow-up (IOP-PE: mean difference, -21.81 [95% CI, -25.57 to -18.04]; P < .001; massed-PE: mean difference, -19.96 [95% CI, -23.56 to -16.35]; P < .001) and were maintained at 6 months (IOP-PE: mean change, -0.21 [95% CI, -3.47 to 3.06]; P = .90; massed-PE: mean change, 3.02 [95% CI, -0.36 to 6.40]; P = .08). Both groups had notable PTSD diagnostic remission at posttreatment (IOP-PE: 48% [95% CI, 36% to 61%] of participants; massed-PE: 62% [95% CI, 51% to 73%] of participants), which was maintained at 6 months (IOP-PE: 53% [95% CI, 40% to 66%] of participants; massed-PE: 52% [95% CI, 38% to 66%] of participants). Most participants demonstrated reliable change on the CAPS-5 (61% [95% CI, 52% to 69%] of participants) and the PCL-5 (74% [95% CI, 66% to 81%] of participants) at the 1-month follow-up.

CONCLUSIONS AND RELEVANCE: These findings suggest that PE can be adapted into compressed treatment formats that effectively reduce PTSD symptoms.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03529435.

PMID:36602803 | DOI:10.1001/jamanetworkopen.2022.49422

JAMA Netw Open. 2023 Jan 3;6(1):e2249591. doi: 10.1001/jamanetworkopen.2022.49591.

ABSTRACT

IMPORTANCE: The addition of consolidative durvalumab to chemoradiation has improved disease control and survival in locally advanced non-small cell lung cancer (NSCLC). However, there remains a need to identify biomarkers for response to this therapy to allow for risk adaptation and personalization.

OBJECTIVES: To evaluate whether TMB or other variants associated with radiation response are also associated with outcomes following definitive chemoradiation and adjuvant durvalumab among patients with locally advanced unresectable NSCLC.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included consecutive patients with unresectable locally advanced NSCLC treated with chemoradiation and adjuvant durvalumab between November 2013 and March 2020 who had prospective comprehensive genomic profiling. This study was completed at a multisite tertiary cancer center. The median (IQR) follow-up time was 26 (21-36) months. Statistical analysis was conducted from April to October 2022.

EXPOSURES: Patients were grouped into TMB-high (≥10 mutations/megabase [mt/Mb]) and TMB-low (<10 mt/Mb) groups and were additionally evaluated by the presence of somatic alterations associated with radiation resistance (KEAP1/NFE2L2) or radiation sensitivity (DNA damage repair pathway).

MAIN OUTCOMES AND MEASURES: The primary outcomes were 24-month local-regional failure (LRF) and progression-free survival (PFS).

RESULTS: In this cohort study of 81 patients (46 [57%] male patients; median [range] age, 67 [45-85] years), 36 patients (44%) had TMB-high tumors (≥10 mt/Mb). Patients with TMB-high vs TMB-low tumors had markedly lower 24-month LRF (9% [95% CI, 0%-46%] vs 51% [95% CI, 36%-71%]; P = .001) and improved 24-month PFS (66% [95% CI, 54%-84%] vs 27% [95% CI, 13%-40%]; P = .003). The 24-month LRF was 52% (95% CI, 25%-84%) among patients with KEAP1/NFE2L2-altered tumors compared with 27% (95% CI, 17%-42%) among patients with KEAP1/NFE2L2-wildtype tumors (P = .05). On Cox analysis, only TMB status was associated with LRF (hazard ratio [HR], 0.17; 95% CI, 0.03-0.64; P = .02) and PFS (HR, 0.45; 95% CI, 0.21-0.90; P = .03). Histology, disease stage, Eastern Cooperative Oncology Group status, programmed cell death ligand 1 expression, and pathogenic KEAP1/NFE2L2, KRAS, and DNA damage repair pathway alterations were not significantly associated with LRF or PFS.

CONCLUSIONS AND RELEVANCE: In this cohort study, TMB-high status was associated with improved local-regional control and PFS after definitive chemoradiation and adjuvant durvalumab. TMB status may facilitate risk-adaptive radiation strategies in unresectable locally advanced NSCLC.

PMID:36602799 | DOI:10.1001/jamanetworkopen.2022.49591

JAMA Netw Open. 2023 Jan 3;6(1):e2249674. doi: 10.1001/jamanetworkopen.2022.49674.

ABSTRACT

IMPORTANCE: Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma with increasing incidence. Cytotoxic chemotherapy and checkpoint inhibitors provide treatment options in the metastatic setting; however, there are no approved or standard of care targeted therapy treatment options.

OBJECTIVE: To identify actionable alterations annotated by the OncoKB database therapeutic evidence level in association with tumor mutation burden (TMB).

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective, cross-sectional study using data from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange, a multicenter international cancer consortium database. Patients with MCC were enrolled in participating institutions between 2017 and 2022. Data from version 11.0 of the database were released in January 2022 and analyzed from April to June 2022.

MAIN OUTCOMES AND MEASURES: The main outcome was the percentage of patients with high TMB and OncoKB level 3B and 4 alterations.

RESULTS: A total of 324 tumor samples from 313 patients with MCC (107 women [34.2%]; 287 White patients [91.7%]; 7 Black patients [2.2%]) were cataloged in the database. The median (range) number of alterations was 4.0 (0.0-178.0), with a mean (SD) of 13.6 (21.2) alterations. Oncogenic alterations represented 20.2% of all alterations (862 of 4259 alterations). Tissue originated from primary tumor in 55.0% of patients (172 patients) vs metastasis in 39.6% (124 patients). TMB-high (≥10 mutations per megabase) was present in 26.2% of cases (82 patients). Next-generation sequencing identified 55 patients (17.6%) with a level 3B variation for a Food and Drug Administration-approved drug for use in a biomarker-approved indication or approved drug in another indication. An additional 8.6% of patients (27 patients) had a level 4 variation. Actionable alterations were more common among high TMB cases, with 37 of 82 patients (45.1%) harboring level 3 alterations compared with only 18 of 231 patients (7.8%) with low TMB. The most common level 3B gene variants included PIK3CA (12 patients [3.8%]), BRCA1/2 (13 patients [4.2%]), ATM (7 patients [2.2%]), HRAS (5 patients [1.6%]), and TSC1/2 (6 patients [1.9%]). The most common level 4 variants include PTEN (13 patients [4.1%]), ARID1A (9 patients [2.9%]), NF1 (7 patients [2.2%]), and CDKN2A (7 patients [2.2%]). Copy number alterations and fusions were infrequent. In 61.0% of cases (191 cases), a PanCancer pathway was altered, and 39.9% (125 cases) had alterations in multiple pathways. Commonly altered pathways were RTK-RAS (119 patients [38.0%]), TP53 (103 patients [32.9%]), cell cycle (104 patients [33.2%]), PI3K (99 patients [31.6%]), and NOTCH (93 patients [29.7%]). In addition, oncogenic DNA mismatch repair gene alterations were present in 8.0% of cases (25 patients).

CONCLUSIONS AND RELEVANCE: In this cross-sectional retrospective study of alterations and TMB in MCC, a minority of patients had potentially actionable alterations. These findings support the investigation of targeted therapies as single agent or in combination with immunotherapy or cytotoxic chemotherapy in selected MCC populations.

PMID:36602798 | DOI:10.1001/jamanetworkopen.2022.49674

JAMA Netw Open. 2023 Jan 3;6(1):e2249720. doi: 10.1001/jamanetworkopen.2022.49720.

ABSTRACT

IMPORTANCE: Treatment options are limited for patients with advanced pancreatic ductal adenocarcinoma (PDAC) beyond first-line 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX), with such individuals commonly being treated with gemcitabine and nab-paclitaxel.

OBJECTIVE: To determine whether NPC-1C, an antibody directed against MUC5AC, might increase the efficacy of second-line gemcitabine and nab-paclitaxel in patients with advanced PDAC.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase II clinical trial enrolled patients with advanced PDAC between April 2014 and March 2017 whose disease had progressed on first-line FOLFIRINOX. Eligible patients had tumors with at least 20 MUC5AC staining by centralized immunohistochemistry review. Statistical analysis was performed from April to May 2022.

INTERVENTIONS: Patients were randomly assigned to receive gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) administered intravenously on days 1, 8, and 15 of every 4-week cycle, with or without intravenous NPC-1C 1.5 mg/kg every 2 weeks.

MAIN OUTCOMES AND MEASURES: The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rate (ORR), and safety. Pretreatment clinical variables were explored with Cox proportional hazards analysis.

RESULTS: A total of 78 patients (median [range] age, 62 [36-78] years; 32 [41%] women; 9 [12%] Black; 66 [85%] White) received second-line treatment with gemcitabine plus nab-paclitaxel (n = 40) or gemcitabine plus nab-paclitaxel and NPC-1C (n = 38). Median OS was 6.6 months (95% CI, 4.7-8.4 months) with gemcitabine plus nab-paclitaxel vs 5.0 months (95% CI, 3.3-6.5 months; P = .22) with gemcitabine plus nab-paclitaxel and NPC-1C. Median PFS was 2.7 months (95% CI, 1.9-4.1 months) with gemcitabine plus nab-paclitaxel vs 3.4 months (95% CI, 1.9-5.3 months; P = .80) with gemcitabine plus nab-paclitaxel and NPC-1C. The ORR was 3.1% (95% CI, 0.4%-19.7%) in the gemcitabine plus nab-paclitaxel and NPC-1C group and 2.9% (95% CI, 0.4%-18.7%) in the gemcitabine plus nab-paclitaxel group. No differences in toxicity were observed between groups, except that grade 3 or greater anemia occurred more frequently in patients treated with gemcitabine plus nab-paclitaxel and NPC-1C than gemcitabine plus nab-paclitaxel (39% [15 of 38] vs 10% [4 of 40]; P = .003). The frequency of chemotherapy dose reductions was similar in both groups (65% vs 74%; P = .47). Lower performance status, hypoalbuminemia, PDAC diagnosis less than or equal to 18 months before trial enrollment, lymphocyte-to-monocyte ratio less than 2.8, and CA19-9 greater than 2000 IU/mL were independently associated with poorer survival.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of advanced PDAC, NPC-1C did not enhance the efficacy of gemcitabine/nab-paclitaxel. These data provide a benchmark for future trials investigating second-line treatment of PDAC.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01834235.

PMID:36602796 | DOI:10.1001/jamanetworkopen.2022.49720