Highlights
- •Clinical trials seldom report timing, duration and recurrence of adverse events.
- •Duration and recurrence of adverse events are crucial in clinical decision making.
- •A novel method and illustration are used to describe adverse event trajectories.
- •Methods use readily available data and could be reported in all clinical trials.
- •Methods are applicable to any new or emerging cancer treatments.
Abstract
Background
Clinical trials report adverse events (AEs) in a dense table focusing on the frequency
of ‘worst grade’ AEs experienced over the duration of treatment. There is usually
no granular information provided on the timing and trajectory of AEs or whether they
are likely to worsen, improve, or remain constant over time.
Patients and methods
Non-hematologic (NH) AE data was extracted from the CALYPSO trial comparing carboplatin
with pegylated liposomal doxorubicin (CD) to carboplatin with paclitaxel (CP) in recurrent
ovarian cancer (ROC). Generalised estimating equations (GEE) were used to assess the
risk and trajectory of combined Grade 2 or higher (G2+) AE and of each specific AE.
The risk of G2+AE was also compared between treatment arms.
Results
The study included 976 patients and AE were reported for the duration of treatment.
Most patients experienced at least one G2+NHAE (CP:CD, 96.0%:80.6%). Risk of combined
G2+AE increased with CP (4.1% per-cycle) but decreased with CD (0.8%, P <0.01). When alopecia and sensory neuropathy were excluded, risk of G2+ AE decreased
by 2.7% per-cycle, with no significant difference between treatment arms. G2+ nausea
improved (15.2% per-cycle, P <0.01). G2+ sensory neuropathy worsened (29.3% per-cycle, P <0.01). Fatigue was stable (17% per-cycle, P =0.06) whilst G2+ pain decreased over time (13.4% per-cycle, P <0.01), with no difference between treatment arms.
Conclusion
Existing trial data can be used to provide AE trajectories as illustrated here for
ROC. These trajectories have utility in guiding treatment choice and potentially optimising
AE management with novel therapies and treatment combinations.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of CancerAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Talking about toxicity - ‘what we’ve got here is a failure to communicate’.N Engl J Med. 2019; 381: 1406-1408
- Reporting harms more transparently in trials of cancer drugs.BMJ Br Med J (Clin Res Ed). 2018; 363: k4383
- The imperative for a new approach to toxicity analysis in Oncology clinical trials.Oxford University Press, 2015
- Beyond maximum grade: modernising the assessment and reporting of adverse events in haematological malignancies.The Lancet Haematology. 2018; 5: e563-e598
- The evolution and application of toxicity criteria.Semin Radiat Oncol. 2002; 12: 1-3
National Cancer Institute. Common Terminology criteria for adverse events (CTCAE) version 5. .
- Patient-reported outcomes and the evolution of adverse event reporting in oncology.J Clin Oncol. 2007; 25: 5121-5127
- The predictive value of cumulative toxicity for quality of life in patients with metastatic colorectal cancer during first-line palliative chemotherapy.Canc Manag Res. 2018; 10: 3015-3021
- Frequency of low-grade adverse events and quality of life during chemotherapy determine patients’ judgement about treatment in advanced-stage thoracic cancer.(Original Article).Support Care Canc. 2019; 27: 3563
- Patient preferences in advanced or recurrent ovarian cancer.Cancer. 2014; 120: 3651-3659
- Pegylated liposomal Doxorubicin and Carboplatin compared with Paclitaxel and Carboplatin for patients with platinum-sensitive ovarian cancer in late relapse.J Clin Oncol: official journal of the American Society of Clinical Oncology. 2010; 28: 3323
- Variations in patient preferences over side effects of treatments for ovarian cancer: baseline results of a randomized controlled clinical trial.Gynecol Oncol. 2017; 145: 26-27
- A systematic review of patient values, preferences and expectations for the treatment of recurrent ovarian cancer.Gynecol Oncol. 2017; 146: 392-398
Article info
Publication history
Published online: March 20, 2021
Accepted:
February 2,
2021
Received in revised form:
January 19,
2021
Received:
October 25,
2020
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
