Introduction

Kaplan-Meier survival analysis, the cornerstone of evaluating efficacy of oncology drugs in randomised controlled trials (RCTs), assumes censored patients are neither healthier nor sicker than those followed. We sought to examine whether censoring patterns differ between the control and experimental arms in one oncology journal that mandates the reporting of the number of patients censored.

Methods

In this retrospective review, proportion of censoring and study design data were gathered from RCTs published in The Lancet Oncology that reported Kaplan-Meier curves between May 2018 and August 2019. Differential censoring rates were analysed at the 1st, 3rd, 6th, and overall time points in each study. Analysis was stratified by curves reporting progression-free survival (PFS) or overall survival (OS) end-points.

Results

Of the 160 articles reviewed, 29 studies with 51 Kaplan-Meier curves were eligible. In both OS (N = 25) and PFS curves (N = 26), the absolute weighted difference in censoring between the control and experimental arms was initially positive, indicating more censoring in the control arm (first time point OS: 0.32%; PFS: 2.00%). The absolute difference then became negative, indicating more censoring in the experimental arm as time progressed (end-of-study OS: -7.54%; PFS: -9.09%).

Conclusion

Differences in censoring between control and experimental arms of cancer RCTs suggest that there could be systematic bias present at various study time points that may influence key results. Further investigation is needed, as possible reasons include study assignment disappointment, inappropriate follow-up length, lack of efficacy, or intolerable toxicity, each predominant at specific time points after randomisation.

This retrospective review assesses the frequency of surrogate measures used for the first time vs subsequent times in a cancer setting and the surrogate’s strength of correlation with patient-centered outcomes.

Background

Financial costs from cancer treatment are increasingly recognized, but what has historically been underrecognized is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BSC), with the assumption that without this drug, a patient could have been treated with observation, home palliative care or hospice services, with minimal time seeking medical care.

Methods

We searched all FDA approvals (2009 - March 2022) for randomized trials that used BSC as a treatment option for an anti-tumor drug in the metastatic setting and abstracted data on treatment related activities. We then estimated time spent on these activities using previously calculated times.

Results

Of the 13 drugs tested against BSC, nine studies demonstrated an improvement in median OS (median 2.1 months). The median monthly time spent for patients in the intervention arm of BSC trials was 15.8 h.

Conclusion

Time is a valuable resource for people who have cancer, but especially for patients who may have few to no remaining treatment options, and yet, we found that patients can spend up to 16 h in anti-cancer drug related activities per month.

Policy summary

Because survival outcomes are variable for patients being treated in later lines of therapy, time resources are a valuable consideration in the treatment plan.

Abstract: Background: Financial costs from cancer treatment are increasingly recognized, but what has historically been underrecognized is the time cost of therapy. We sought to estimate the time burden of anti-cancer drugs approved based on comparisons to best supportive care (BCS), with the assumption that without this drug, a patient could have been treated with observation, home palliative care or hospice services, with minimal time seeking medical care. Methods: We searched all FDA approvals (2009 - March 2022) for randomized trials that used BCS as a treatment option for an anti-tumor drug in the metastatic setting and abstracted data on treatment related activities. We then estimated time spent on these activities using previously calculated times. Results: Of the 13 drugs tested against BSC, nine studies demonstrated an improvement in median OS (median 2.1 months). The median monthly time spent for patients in the intervention arm of BSC trials was 15.8 hours. Conclusion: Time is a valuable resource for people who have cancer, but especially for patients who may have few to no remaining treatment options, and yet, we found that patients can spend up to 16 hours in anti-cancer drug related activities per month.

Aims patients & methods

In this retrospective review, we sought to estimate the proportion of patients in the USA with advanced or metastatic cancer who are eligible for and may respond to recommended first-line cytotoxic chemotherapy based on National Comprehensive Cancer Network treatment guidelines.

Results

Among 609,640 patients, we estimate 479,823 (78.7%, 95% CI: 78.6-78.8%) may be eligible for cytotoxic chemotherapy while 189,159 out of 609,640 patients (31.0%, 95% CI: 30.9-31.1%) may have achieved treatment response. The average objective response rate from these regimens was 48.6% (range 9.2 to 90.6%).

Conclusion

Given the large role of cytotoxic agents in cancer, drug development in this space may remain of interest in specific cancer types, and regulatory approval of novel oncology drugs may justify head-to-head comparisons against cytotoxic regimens.

Background

As progress continues in oncology drug development, this study aimed to examine whether the previously established association between drug dose and efficacy in the era of cytotoxic therapies remains true in today's phase I dose-escalation oncology trials.

Methods

A systematic review of early-phase dose-finding trials of single-agent oncology drugs from 2015 to 2018 was conducted to examine the relationship between drug dose and objective responses. Cancer-specific trials were included if they determined maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Data related to the study drug, study design, treatment response, cancer type, dose levels, MTD, and RP2D were all collected. Dose level was categorized into 4 categories (≤40%, 41%-80%, 81%-120%, and >120% of the RP2D) and was further analyzed by class of drug.

Results

A total of 175 phase I studies were identified, with a total of 7,330 patients showing a median response rate of 5% (range, 0%-83%) across trials. A total of 93 trials with 2,506 participants had response data corresponding to drug dose level. In this subset, the median response rate was 5% (range, 0%-83%) across trials. Across all participants in this subset, the response rate was 12% (57 of 491) among those in the dose range of ≤40% of RP2D, 17% (95 of 562) among those in 41% to 80% of RP2D, 23% (272 of 1,206) among those in 81% to 120% of RP2D, and 29% (71 of 247) among those in >120% of RP2D (P<.001). The response rate at ≤40% of RP2D for targeted antibody was 5%, 4% for cellular therapy, 19% for immunotherapy, and 21% for small-molecule targeted inhibitors.

Conclusions

Whereas our study of published phase I trials continued to show a low response rate consistent with earlier studies, the relationship between response and dose does not always peak at 81% to 120% of RP2D anymore, likely due to the use of novel immunotherapy and targeted agents with distinct efficacy and toxicity patterns.

e18228 Background: Oncology drug development has shifted away from cytotoxic agents, while they remain widely used in clinical practice. We sought to estimate the proportion of U.S. patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy alone based on National Comprehensive Cancer Network (NCCN) treatment guidelines. Methods: This retrospective review used publicly available annual mortality data from the American Cancer Society to estimate the number of patients who would have presented with advanced or metastatic disease. Published clinical trials of first-line cytotoxic-only regimens as advised by the NCCN were used to calculate overall response rates (complete plus partial response) for each cancer type. Chemotherapies in combination with immunotherapy or biologic agents were excluded. Mean response rate was used when there was more than one recommended regimen. The main outcome was to identify the proportion of patients with advanced or metastatic cancer who are eligible for and may respond to standard first-line cytotoxic chemotherapy regimens based on cancer type. Results: We identified 92 different cytotoxic chemotherapy regimens used in 25 cancer types. Among an estimated 609,640 cancer-related deaths in 2018, 479,823 (78.7%) would be eligible to receive standard first-line cytotoxic chemotherapy. We estimated 189,159 of 609,640 (31.0%) patients to achieve at least partial response. The median objective response rate was 48.6% (range 9.2%-90.6%). The following cancers had the highest response rate to cytotoxic chemotherapy: acute lymphoblastic leukemia (90.6%), acute myeloid leukemia (76.7%), and uterine cancer (75%). The following had the greatest number of patients who may respond to cytotoxic chemotherapy: lung cancer (60,234 of 609,640; 9.9%), colorectal cancer (23,138; 3.8%), and non-Hodgkin lymphoma (14,773; 2.4%). Conclusions: Given the large proportion of patients who may benefit from cytotoxic agents, drug development in this space may warrant continued interest in specific cancer types. Also, the regulatory approval of novel oncology drugs may justify head-to-head comparison against modern chemotherapy regimens.

Background

Determination of the comparative efficacy of one therapy over another for hepatocellular carcinoma (HCC) can be challenging. Application of a recognized value framework to published studies could objectively compare the potential benefit across available therapies.

Materials and methods

An umbrella review of phase III trials for HCC therapies was performed. ASCO Value Framework Net Health Benefit Score version 2 (ASCO-NHB v2) scores, the primary analysis, and European Society of Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 scores, the secondary analysis, were computed using selected drug registration trials. Both scores were compared between drugs that were Food and Drug Administration (FDA)-approved by 2020 and those that were not.

Results

Of the 22 studies identified, nine were FDA-approved and 13 were not. Across 22 trials, the median overall survival (OS) was 9.2 months (range, 1.9-16.4 months), with a median gain of 0.35 month (range, 2.3-3.3 months). HCC therapies that were FDA-approved showed longer OS (median 10.7 v 7.9 months, P < .01) and higher ASCO NHB scores (+18.4 v -5.7 scores, P < .01). The median gain in OS was 2.2 months in the approved treatments compared with -0.3 months in the unapproved group, with no difference in progression-free survival between the two groups.

Conclusion

The nine FDA-approved therapies for HCC have higher mean NHB score than those that were not FDA-approved. The application of ASCO-NHB v2 and other proposed value frameworks could examine data of future therapies for HCC through a patient-oriented approach.

Background

Identifying ineffective practices that have been used in oncology is important in reducing wasted resources and harm. We sought to examine the prevalence of practices that are being used but have been shown in RCTs to be ineffective (medical reversals) in published oncology studies.

Methods

We cross-sectionally analyzed studies published in three high-impact oncology medical journals (2009-2018). We abstracted data relating to the frequency and characterization of medical reversals.

Results

Of the 64 oncology reversals, medications (44%) represented the most common intervention type (39% were targeted). Fourteen (22%) were funded by pharmaceutical/industry only and 56% were funded by an organization other than pharmaceutical/industry. The median number of years that the practice had been in use prior to the reversal study was 9 years (range 1-50 years).

Conclusion

Here we show that oncology reversals most often involve the administration of medications, have been practiced for years, and are often identified through studies funded by non-industry organizations.