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Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.
In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.
They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).
Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.
“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.
This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.
However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.
The authors also looked at whether the studies that compared immunotherapies with nonimmunological therapies might show a different effect, but they still found a significantly higher benefit in men, compared with women.
The overall study population was two-thirds male and one-third female. The checkpoint inhibitors used were ipilimumab, tremelimumab, nivolumab, and pembrolizumab, and the trials were conducted in patients with melanoma, non–small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial tumors, gastric tumors, and mesothelioma.
Men have almost double the risk of mortality from cancer than do women, the authors said, with the greatest differences seen in melanoma, lung cancer, larynx cancer, esophagus cancer, and bladder cancer.
“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”
Despite this, sex is rarely taken into account when new therapeutic approaches are tested, the authors said.
They also commented on the fact that there was a relatively low number of women included in each trial, an issue that was recognized as far back as the 1990s as a major problem in medical trials.
“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” they wrote.
They noted that they couldn’t exclude the possibility that the effect may be the result of other variables that were distributed differently between the sexes. However, they also qualified this by saying that variables known to affect the efficacy of immune checkpoint inhibitors, such as PD-L1 expression and mutation status, were not likely to explain the results.
Given their findings, the authors said a patient’s sex should be taken into account when weighing the risks and benefits of checkpoint inhibitors given the magnitude of benefit was sex-dependent. They also called for future immunotherapy studies to include more women.
No funding or conflicts of interest were declared.
SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.
While cancer immunotherapy represents one of the most significant clinical advances in cancer treatment in the past decade, the basic but important clinical question about different effects between men and woman has not been addressed until now. The authors of this study are to be congratulated on such a comprehensive and well-conducted analysis, but the data does not completely support their final conclusion that checkpoint inhibitors benefit men more than women.
There are a large number of baseline characteristics of solid tumors that might differ between men and women and that have also been reported to impact the outcomes of patients treated with checkpoint inhibitors. Some of these may be lifestyle or behavioral characteristics – such as different smoking habits between men and women with non–small cell lung cancer – or differences in the distribution of oncogenic driver mutations between men and women.
We should therefore be cautious in jumping to conclusions and changing the current standard of care with respect to checkpoint inhibitors. In particular, we should not be denying treatment to women who are otherwise indicated for checkpoint inhibitors, based on these findings.
Omar Abdel-Rahman, MD, is from the clinical oncology department of the faculty of medicine at Ain Shams University in Cairo and from the Tom Baker Cancer Centre in Calgary. These comments are taken from an accompanying editorial (Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045[18]30270-5.) No conflicts of interest were declared.
While cancer immunotherapy represents one of the most significant clinical advances in cancer treatment in the past decade, the basic but important clinical question about different effects between men and woman has not been addressed until now. The authors of this study are to be congratulated on such a comprehensive and well-conducted analysis, but the data does not completely support their final conclusion that checkpoint inhibitors benefit men more than women.
There are a large number of baseline characteristics of solid tumors that might differ between men and women and that have also been reported to impact the outcomes of patients treated with checkpoint inhibitors. Some of these may be lifestyle or behavioral characteristics – such as different smoking habits between men and women with non–small cell lung cancer – or differences in the distribution of oncogenic driver mutations between men and women.
We should therefore be cautious in jumping to conclusions and changing the current standard of care with respect to checkpoint inhibitors. In particular, we should not be denying treatment to women who are otherwise indicated for checkpoint inhibitors, based on these findings.
Omar Abdel-Rahman, MD, is from the clinical oncology department of the faculty of medicine at Ain Shams University in Cairo and from the Tom Baker Cancer Centre in Calgary. These comments are taken from an accompanying editorial (Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045[18]30270-5.) No conflicts of interest were declared.
While cancer immunotherapy represents one of the most significant clinical advances in cancer treatment in the past decade, the basic but important clinical question about different effects between men and woman has not been addressed until now. The authors of this study are to be congratulated on such a comprehensive and well-conducted analysis, but the data does not completely support their final conclusion that checkpoint inhibitors benefit men more than women.
There are a large number of baseline characteristics of solid tumors that might differ between men and women and that have also been reported to impact the outcomes of patients treated with checkpoint inhibitors. Some of these may be lifestyle or behavioral characteristics – such as different smoking habits between men and women with non–small cell lung cancer – or differences in the distribution of oncogenic driver mutations between men and women.
We should therefore be cautious in jumping to conclusions and changing the current standard of care with respect to checkpoint inhibitors. In particular, we should not be denying treatment to women who are otherwise indicated for checkpoint inhibitors, based on these findings.
Omar Abdel-Rahman, MD, is from the clinical oncology department of the faculty of medicine at Ain Shams University in Cairo and from the Tom Baker Cancer Centre in Calgary. These comments are taken from an accompanying editorial (Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045[18]30270-5.) No conflicts of interest were declared.
Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.
In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.
They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).
Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.
“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.
This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.
However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.
The authors also looked at whether the studies that compared immunotherapies with nonimmunological therapies might show a different effect, but they still found a significantly higher benefit in men, compared with women.
The overall study population was two-thirds male and one-third female. The checkpoint inhibitors used were ipilimumab, tremelimumab, nivolumab, and pembrolizumab, and the trials were conducted in patients with melanoma, non–small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial tumors, gastric tumors, and mesothelioma.
Men have almost double the risk of mortality from cancer than do women, the authors said, with the greatest differences seen in melanoma, lung cancer, larynx cancer, esophagus cancer, and bladder cancer.
“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”
Despite this, sex is rarely taken into account when new therapeutic approaches are tested, the authors said.
They also commented on the fact that there was a relatively low number of women included in each trial, an issue that was recognized as far back as the 1990s as a major problem in medical trials.
“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” they wrote.
They noted that they couldn’t exclude the possibility that the effect may be the result of other variables that were distributed differently between the sexes. However, they also qualified this by saying that variables known to affect the efficacy of immune checkpoint inhibitors, such as PD-L1 expression and mutation status, were not likely to explain the results.
Given their findings, the authors said a patient’s sex should be taken into account when weighing the risks and benefits of checkpoint inhibitors given the magnitude of benefit was sex-dependent. They also called for future immunotherapy studies to include more women.
No funding or conflicts of interest were declared.
SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.
Cancer immunotherapy using checkpoint inhibitors may achieve greater mortality reductions in men than they do in women, new research has suggested.
In a meta-analysis and systematic review published in Lancet Oncology, researchers analyzed 20 randomized, controlled trials of immune checkpoint inhibitors that included detail on overall survival and patients’ sex; altogether, these studies involved 11,351 patients with advanced or metastatic cancers.
They found that while men treated with checkpoint inhibitors had a significant 28% reduced risk of death, compared with male controls, the survival benefit in women was smaller (14% reduced risk of death, compared with female controls).
Fabio Conforti, MD, from the European Institute of Oncology, Milan, and coauthors commented that the magnitude of the difference between the effect seen men and that in women was clinically significant.
“The pooled reduction of risk of death was double the size for male patients than for female patients – a difference that is similar to the size of the difference in survival benefit observed between patients with non–small cell lung cancer with PD-L1 positive (greater than 1%) tumors versus negative tumors, who were treated with anti-PD-1,” they wrote.
This difference between the benefit seen men and that in women was evident across all the subgroups in the study, which included subgroups based on cancer histotype, line of treatment, drugs used, and type of control.
However there was greater heterogeneity in the magnitude of the effect of checkpoint inhibitors on mortality in men than there was in women. The authors suggested this could be explained by the fact that the drugs have lower efficacy in women and this may therefore reduce the variability of results when compared with those in men.
The authors also looked at whether the studies that compared immunotherapies with nonimmunological therapies might show a different effect, but they still found a significantly higher benefit in men, compared with women.
The overall study population was two-thirds male and one-third female. The checkpoint inhibitors used were ipilimumab, tremelimumab, nivolumab, and pembrolizumab, and the trials were conducted in patients with melanoma, non–small cell lung cancer, head and neck cancer, renal cell carcinoma, urothelial tumors, gastric tumors, and mesothelioma.
Men have almost double the risk of mortality from cancer than do women, the authors said, with the greatest differences seen in melanoma, lung cancer, larynx cancer, esophagus cancer, and bladder cancer.
“This male-biased mortality is hypothesized to reflect differences not only in behavioral and biological factors, including causes of cancer and hormonal regulation, but also in the immune system.”
Despite this, sex is rarely taken into account when new therapeutic approaches are tested, the authors said.
They also commented on the fact that there was a relatively low number of women included in each trial, an issue that was recognized as far back as the 1990s as a major problem in medical trials.
“Our results further highlight this problem, showing clinically relevant differences in the efficacy of two important classes of immunological drugs, namely anti–CTLA-4 and anti–PD-1 antibodies, when compared with controls in male and female patients with advanced solid tumors,” they wrote.
They noted that they couldn’t exclude the possibility that the effect may be the result of other variables that were distributed differently between the sexes. However, they also qualified this by saying that variables known to affect the efficacy of immune checkpoint inhibitors, such as PD-L1 expression and mutation status, were not likely to explain the results.
Given their findings, the authors said a patient’s sex should be taken into account when weighing the risks and benefits of checkpoint inhibitors given the magnitude of benefit was sex-dependent. They also called for future immunotherapy studies to include more women.
No funding or conflicts of interest were declared.
SOURCE: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.
FROM LANCET ONCOLOGY
Key clinical point: Checkpoint inhibitors are linked with greater mortality reductions in men than in women.
Major finding: Checkpoint inhibitors are associated with a 28% reduction in cancer mortality in men and 14% in women.
Study details: Systematic review and meta-analysis of 20 randomized, controlled trials involving 11,351 patients.
Disclosures: No funding or conflicts of interest were declared.
Source: Conforti F et al. Lancet Oncol. 2018 May 16. doi: 10.1016/S1470-2045(18)30261-4.