Underreporting of Research Biopsies from Clinical Trials in Oncology

Parseghian, Christine M.; Raghav, Kanwal; Wolff, Robert A.; Ensor, Joe; Yao, James C.; Ellis, Lee M.; Tam, Alda L.; Overman, Michael J.

doi:10.1158/1078-0432.ccr-17-1449

Cited by 18 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Use of actual tumour biopsies in clinical trials is being recommended to improve characterization of the pharmacodynamic effects of a drug, to understand the molecular processes involved in drug response or resistance, and to identify prognostic and predictive markers (Parseghian et al 2017 ). In general, new tumour material is difficult to acquire, either because of refusal of the patient, the location is difficult to reach or because of inadequate sampling.…”

Section: Discussionmentioning

confidence: 99%

PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane

Kruger

Opdam

Noort

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Purpose Everolimus plus exemestane (EVE/EXE) is a registered treatment option for ER-positive, HER2-negative (ER +/HER2-) metastatic breast cancer (MBC), but resistance mechanisms limit efficacy. We aimed to find markers that might help select patients with a higher chance on benefit from EVE/EXE. Methods Immunohistochemistry (IHC) of PTEN, p-AKT(Thr308), p-AKT(Ser473), p-4EBP1, p-p70S6K, p-S6RP(Ser240/244), p-ERK1/2 and p-S6RP (Ser235/236) was performed on primary tumour tissue and on biopsies immediately taken from ER +/HER2- MBC patients before the start of standard EVE/EXE (Eudract 2013-004120-11). Unsupervised hierarchical clustering was executed to create heatmaps to distinguish subgroups of preferentially activated and less-activated PI3K/MAPK proteins. Uni- and multivariate Cox models were used for associations with PFS. Results Primary tumour tissue from 145 patients was retrieved. Median PFS was 5.4 months. Patients without (neo)adjuvant therapy (p = 0.03) or bone only disease (p = 0.04) had longer PFS on EVE/EXE. In primary tumours, neither single proteins nor PI3K/MAPK-associated heatmap subgroups were significantly associated with PFS. In 21 patients a non-osseous biopsy obtained before dosing was useful for continuous scoring, which demonstrated upregulation of several proteins as compared to readings in corresponding primary tumour tissues. These comparisons revealed that increased expression of p-4EBP1 was significantly associated with worse PFS (multivariate HR 3.69, p = 0.05). Conclusions IHC of single proteins or heatmap subgroups of the differentially activated PI3K/MAPK pathways was not able to discriminate patients on EVE/EXE with poor or better PFS. Upregulation of p-4EBP1 in pre-treatment biopsies as compared to levels in primary tumours pointed towards shorter PFS.

show abstract

Section: Discussionmentioning

confidence: 99%

PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane

Kruger

Opdam

Noort

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…Prior investigations have found that a high rate of clinical trials in oncology remain unpublished. [3][4][5][6][7][8] Due to these findings, recent regulations have been enacted to require clinical trial result reporting. 9 However, these efforts are limited to outcome measures that are part of a clinical trial's statistical analysis plan, and thus are unlikely to include most research biopsies.…”

Section: Discussionmentioning

confidence: 99%

Assessment of Reported Trial Characteristics, Rate of Publication, and Inclusion of Mandatory Biopsies of Research Biopsies in Clinical Trials in Oncology

et al. 2019

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Research biopsies are frequently incorporated within clinical trials in oncology and are often a mandatory requirement for trial enrollment. However, limited information is available regarding the extent and completeness of research biopsy reporting. OBJECTIVES To determine the rate of research biopsy reporting for clinical trials registered in ClinicalTrials.gov and determine the clinical trial factors that correlated with research biopsy reporting. DESIGN, SETTING, AND PARTICIPANTS ClinicalTrials.gov (CTG) was searched for all oncologic therapeutic clinical trials with completion dates between January 1, 2000, and January 1, 2015, with end point category terms including biopsy, biopsies, or tissue. The date of the final publication search was March 12, 2018. Trials conducting only diagnostic biopsies or trials using bone marrow biopsies or liquid biopsies were excluded. Credit for biopsy reporting was given for any mention of performing or results from tissue biopsies in publications. Clinical trials were compared with the highest level of corresponding publication or registry report. Fisher exact test was used for analysis. RESULTS A total of 301 clinical trials were identified, with a median of 37 patients (range, 1-1310 patients) enrolled per trial. After a median follow-up time of 5.8 years from trial completion, 244 of 301 trials (81.1%) reported results: publications in 195 (64.8%) and CTG registry in 49 (16.3%). Reporting of trial results was associated with later-stage trials (phase 2/3) (137 of 153 [89.5%] for phase 2/3 vs 107 of 148 [72.3%] for phase 1 or 1/2 trials; P < .001). Results from research biopsies were reported in 153 of 301 (50.8%) trials or in 153 of 244 (62.7%) trials with published results. Rates varied by type of presentation: 142 of 195 publications (72.8%) vs 11 of 49 CTG reports (22.4%) (P < .001). Conducting mandatory biopsies (82.1% [101 of 123] vs 43.0% [52 of 121]; P < .001), early-phase clinical trials (70.1% [75 of 107] vs 56.9% [78 of 137]; P = .03), and listing the biopsy as a primary objective in CTG (76.3% [45 of 59] vs 58.4% [108 of 185]; P = .01) was associated with improved biopsy reporting. Trials that met their primary end point (71.9% [115 of 160] vs 45.2% [38 of 84]; P < .001) and those published in higher-impact journals (81.1% [77 of 95] vs 65.0% [65 of 100]; P = .01) had improved biopsy reporting. Mandatory biopsies and biopsy reporting increased over time with similar slopes (P = .58). CONCLUSIONS AND RELEVANCE Despite ethical obligations to report research biopsies, only 50.8% of all trials that included a research biopsy-related end point in CTG reported on these biopsy-related results. Improved efforts are needed to report results obtained from research biopsies.

show abstract

“…Conversely, however, research biosampling often leads to translational research overload, especially when the results of such analyses are underreported or never reported. [18][19][20]…”

Section: Streamline Required Study Evaluationsmentioning

confidence: 99%

“…With regard to translational and pharmacodynamics studies, there is no doubt that research biopsies and other assays can yield critical insights and drive scientific progress. Conversely, however, research biosampling often leads to translational research overload , especially when the results of such analyses are underreported or never reported 18‐20 …”

Section: Recommendationsmentioning

confidence: 99%

A unique window of opportunity for practical reform of cancer clinical trials

Vogl

Sallée

Hendricks

et al. 2021

Cancer

View full text Add to dashboard Cite

With rapid modifications in cancer clinical trial operations necessitated by the global pandemic over the last year, there is now an unprecedented opportunity to reform clinical research permanently and solidify innovative practices that have clearly been effective. On the basis of the authors' experience and recommendations from other institutions, a set of specific proposals for clinical trial reform are identified that can be implemented immediately by sponsors, regulators, and study sites. Improvements in clinical trial processes should include increased leverage of technology to facilitate remote trial activity and electronic documents, more efficient and effective communication of adverse event information, and better study design to optimize inclusion criteria, required research procedures, and data collection. The authors suggest that such reform will preserve patient safety and study integrity, address unnecessary and inefficient pre-pandemic constraints, improve access to clinical trials for patients, and speed improvements in cancer care.

show abstract

Underreporting of Research Biopsies from Clinical Trials in Oncology

Cited by 18 publications

References 43 publications

PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane

PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane

Assessment of Reported Trial Characteristics, Rate of Publication, and Inclusion of Mandatory Biopsies of Research Biopsies in Clinical Trials in Oncology

A unique window of opportunity for practical reform of cancer clinical trials

Contact Info

Product

Resources

About