|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Results of the phase 2 crossover component of a phase 2/3 study designed to evaluate the safety and efficacy of an oral formulation of a tetrahydrocannabinol (THC)/cannabidiol (CBD) cannabis extract in the secondary prevention of patients experiencing chemotherapy-induced nausea and vomiting (CINV) revealed that most patients preferred this treatment compared with placebo. These findings were accepted for presentation at the ASCO2 Virtual Scientific Program and released on May 29, 2020.
Despite the use of guideline-concordant prophylaxis for CINV, many patients treated with moderately or highly emetogenic chemotherapy experience these often dreaded adverse effects of chemotherapy, even following the administration of secondary/rescue antiemetic therapy.
The design of this multicenter, placebo-controlled, double-blinded, crossover, phase 2 clinical trial (ACTRN12616001036404), which has been previously described,2 involved enrollment of adult patients with cancer of any type or stage undergoing treatment with moderately or highly emetogenic chemotherapy who reported significant vomiting and/or nausea in the previous cycle of chemotherapy despite receiving guideline-concordant antiemetic therapy. All enrolled patients were scheduled to have at least 2 additional chemotherapy cycles.
Starting on 1 day prior to the first day of the first chemotherapy cycle following study enrollment (A), and continuing through day 5 following initiation of that cycle of chemotherapy, oral THC 2.5 mg/CBD 2.5 mg capsules were administered 3 times daily to study patients and could be titrated to 1 to 4 times daily based on patient response. All study patients then crossed over to receive oral placebo capsules on the same schedule for the second chemotherapy cycle (B). Hence, each patient essentially served as their own control. Guideline-recommended CINV prophylactic therapy was also administered to all patients prior to initiation of each chemotherapy cycle.
The primary endpoint of the phase 2 study involved determination of the percentages of patients reporting a complete response (ie, CR, defined as no nausea or use of rescue medications) between 0 and 120 hours following chemotherapy initiation.
Key secondary study end points included safety preference for cycle A or B study intervention, as well as the percentage of patients experiencing no emesis, no significant nausea, and no use of rescue medication up to 120 hours following initiation of chemotherapy.
Of the 72 patients included in the efficacy analysis who completed at least 2 chemotherapy cycles following study enrollment, the median age was 55 years, approximately three-quarters were female, 58% reported previous use of cannabis (although use of other sources of cannabis were not permitted during the study), and 55% received potentially curative therapy. The most commonly received chemotherapy regimen was a doxorubicin plus cyclophosphamide-based regimen, which was administered to 26% of patients.
Significantly higher rates of CR (25% vs 14%; P =.04), no significant nausea (21% vs 10%; P =.03), and use of rescue medication (28% vs 15%; P =.03) were reported during cycle A compared with cycle B, respectively. The study endpoint of no emesis was reported by 69% and 57% of patients for cycle A and cycle B, respectively (P =.05).
Notably, 83% of patients reported a preference for the study intervention administered in cycle A over that given to them during cycle B.
For the 78 patients included in the safety analysis, no serious adverse events were attributed to THC/CBD, although reported frequencies of sedation (19% vs 4%), dizziness (10% vs 1%), and disorientation (3% vs 0%) were higher during administration of THC/CBD compared with placebo, respectively.
Some of the study limitations identified by the study presenter Peter Grimison, MBBS, MPH, PhD, FRACP, clinical associate professor at the Chris O’Brien Lifehouse, Sydney Cancer Center in New South Wales, included concomitant use of olanzapine in only 4% of patients, and nonparticipation of a high percentage of those initially identified as being eligible for the study (due to current cannabis use, refusal to stop driving during study duration, psychiatric comorbidities, and because of the crossover design of the study, as well as other reasons).
“Based on these positive results, the definitive parallel phase 3 trial component continues to accrue,” Dr Grimison noted in his concluding remarks.
Disclosure: Research funding for this study of a proprietary formulation of a cannabis extract developed by Tilray was provided by the New South Wales Ministry of Health. For a full list of disclosures, please refer to the study abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
- Grimison PS, Stockler MR, Kirby A, et al. Results of crossover phase II component of randomized placebo-controlled trial evaluating oral THC/cannabis extract for refractory chemotherapy-induced nausea and vomiting (CINV). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 12008.
- Mersiades A, Tognela A, Haber PS, et al. Pilot and definitive randomised double-blind placebo-controlled trials evaluating an oral cannabinoid-rich THC/CBD cannabis extract for secondary prevention of chemotherapy-induced nausea and vomiting. Ann Oncol. 2018;29(suppl 8):VII640.