Immunotherapy Should Not Be Withheld Because of Sex, Age, or PS

Pam Harrison

August 27, 2020

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient's sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), a new meta-analysis concludes.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors conclude.

Asked whether there have been such instances, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: "We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

"And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful," he added.

The study was published online August 7 in JAMA Network Open.

"The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies," the authors comment.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. "Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22)," the authors explain.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of type of cancer, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were programmed death receptor 1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients' sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients' age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients' ECOG PS.

Table. Pooled HRs for ICIs vs Control Therapies

  Men Women
Overall 0.75 0.79
Line of Rx    
First 0.75 0.72
Subsequent 0.75 0.83
Agent of immunoRx    
CTLA-4 inhibitor 0.80 0.86
PD-1/PD-L1 inhibitor 0.74 0.76
Intervention strategy    
ICI alone 0.75 0.83
ICI combined with non-ICI 0.76 0.69


No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators point out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with ECOG PS O and ECOG PS 1 or greater. The overall survival benefit was 0.81 for those with ECOG 0 PS and 0.79 for those with ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

JAMA Netw Open. Published online August 7, 2020. Full text

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