Spontaneous regression of solid tumours in the absence of anti-cancer treatment has been known to occur, but it is extremely rare, a recent study has confirmed, with the study team saying the chances are “almost zero”.
After pooling placebo response rates from 45 cancer drug trials in advanced solid tumours, the researchers found a complete response of 0% and a partial response of 1%.
“Now we can answer our patients,” tweeted lead investigator Dr Bishal Gyawali of Queen’s University, Canada. Without treatment, “the chance of complete response is almost zero and should not be relied upon. It’s next to a miracle.
“Hopefully, these data will convince our patients to not abandon cancer therapy.”
The study was published in The Lancet eClinicalMedicine.
A recent national survey by the American Society of Clinical Oncology (ASCO) had found that 40% of Americans believed their cancer could be completely cured with alternative treatments alone.
This belief may be fuelled by anecdotal reports shared among people with cancer, Gyawali noted in his tweet.
Concerned that such anecdotes might dissuade some patients from seeking treatment, he and colleagues sought to better understand the frequency with which advanced solid tumours undergo spontaneous regression.
The team analysed placebo response rates in 45 randomised controlled trials in which cancer drugs were used to treat advanced solid tumours.
The authors note that the “best estimate for the chances of spontaneous regression can be inferred through the placebo response rates in randomised trials since placebo, by definition, are inert substances that do not have any anti-tumour effects of their own”.
The trials, published between 2015 and 2021, involved a total of 5 684 patients. The authors clarified that placebo consisted of a monotherapy or best supportive care and was not used in combination therapy, such as chemotherapy or immunotherapy plus placebo.
Of the 4 760 patients evaluable for an objective response rate in the placebo arm, 94 (1.97%) achieved an objective response. A pooled analysis revealed an objective response rate of 1%.
Of 3 808 patients who could be evaluated for partial or complete responses, only four (0.1%) achieved a complete response. The pooled complete response rate was 0%. In addition, just more than 2% of patients who received placebo (83 of 3 808) achieved a partial response, with a pooled partial response rate of 1% across trials.
Gyawali and colleagues found it “reassuring” that their pooled placebo response rates were in line with those in two other studies, which showed an objective response rate of 2% with placebo or no active treatment among patients with advanced solid tumours.
“Thus, we can safely tell our patients that the chances of response without treatment are probably 1%, and not more than 2% even in the most optimistic scenario,” the authors write.
They note, however, that subgroup analyses based on tumour types revealed slightly higher objective response rates in the placebo arm for prostate cancer (7%) and sarcoma (4%).
The higher objective response rate in prostate cancer might be explained by the therapeutic effect of prednisone or by the ongoing use of androgen blockade outside the study.
“However, a 4% response rate in sarcoma patients is intriguing, and lacks clear explanation,” the team writes.
Potential limitations of the study include possible publication bias and heterogeneity of studies evaluated.
Despite these limitations, Gyawali and colleagues conclude that patients “should not expect complete regression of cancers without treatment”.
Dr Bhavana Pothuri, who was not involved in the research, was not surprised by the “very low rate” of partial and complete responses among patients who receive placebos.
This study provides “important information as we speak to patients” in trials and shows them the “substantial benefit” cancer treatments can provide, Pothuri, gynaecologic oncologist at NYU Langone Perlmutter Cancer Centre, New York City, told Medscape Medical News.
Study details
Objective response rate of placebo in randomized controlled trials of anticancer medicines
Arushi Sachdev, Isobel Sharpe, Meghan Bowman, Christopher Booth, Bishal Gyawali.
Published in The Lancet eClinicalMedicine on 24 November 2022
Summary
Background
Spontaneous regression of advanced solid tumours is infrequent but may occur. Quantifying response rates from placebo in cancer drug trials may provide important information for physicians, patients, and regulators. We aimed to provide a pooled placebo response rate from drug trials in advanced solid tumours.
Methods
We pooled the overall response rate (ORR), complete response rate (CR) and partial response rates (PR) in the placebo arm of placebo-controlled randomised controlled trials (RCTs) of cancer drugs for advanced solid tumours published during 2015–2021 using random-effects model.
Findings
45 phase 3 RCTs including 5684 patients on placebo met our inclusion criteria and formed the study cohort. The pooled overall ORR, CR and PR rates in the placebo arm were 1% (95% CI, 0%–2%), 0% (95% CI, 0%–0%), and 1% (95% CI, 0%–2%) respectively. Higher placebo responses were observed in prostate cancer and sarcoma trials.
Interpretation
Overall, 1% patients with advanced solid tumours can expect to achieve some response even in absence of treatment. However, complete regression without treatment is extremely rare, almost zero percent. This information will be helpful to patients in their decisions, as well as regulators in evaluating cancer drugs’ efficacy based on response rates alone.
Medscape article – Spontaneous Cancer Regression Extremely Rare (Open access)
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