Pooling data across heterogeneous cancer types and patient populations with myriad baseline characteristics might oversimplify a very complicated picture, he said. Roughly a third of the patients represented in the meta-analysis were treated for non-small-cell lung cancer (NSCLC), and female patients with this type of cancer are more likely than men to be nonsmokers. Smokers are more likely than never-smokers to benefit from immune checkpoint blockade for NSCLC in the second-line setting, Dr Abdel-Rahman noted.

“We don’t really know if some of these patients are more likely to benefit because they are men or because of smoking status,” he said.

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Particular tumor subtypes, with different sensitivities to immunotherapy, might also be more common in one sex or the other.

“We know also that a couple of common driver mutations, particularly in lung cancer, are more common in women than men, and that people whose tumors harbor these mutations are less likely to benefit from immune checkpoint inhibition,” Dr Abdel-Rahman said.

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There is some reason to suspect that prospective studies might confirm that a real difference in observed benefit exists between men and women, however.

“Sex hormones may play a role in the modulation of the PD1/PD-L1 axis, although the published literature is mainly restricted to animal studies,” Dr Duma said. Women are more likely to have autoimmune diseases than are men, and to mount stronger innate and adaptive immune responses, she noted. The more “hyperactive” immune systems seen in females could represent a selection pressure for the evolution of acquired tumor immune-evasion mechanisms, but experts say more research is needed.

“We need further studies to better understand our observations, but [our] findings bring attention to a very important issue: women are biologically different from men and may require closer monitoring while receiving treatment with anti-PD1 therapy for metastatic melanoma,” Dr Duma said.

Meanwhile, patients should be told how to recognize IRAEs. Most are familiar with the nausea, vomiting, and diarrhea that can be associated with conventional cytotoxic cancer treatments — but there is a long and growing list of newly reported adverse events associated with immune checkpoint inhibitors, Dr Duma said.

“We continue to learn every day about possible risk factors and associations for these adverse events — but a lot of research is still needed,” she concluded.


  1. Conforti F, Pala L, Bagnardi V, et al. Cancer immunotherapy efficacy and patients’ sex: a systematic review and meta-analysis. Lancet Oncol. 2018;19:737-746. doi: 10.1016/S1470-2045(18)30261-4
  2. Duma N, Paludo J, Enninga EA, et al. Sex differences in tolerability to anti-PD1 therapy: are we all equal? J Clin Oncol. 2018;36(suppl):abstr 9547.
  3. Abdel-Rahman O. Does a patient’s sex predict the efficacy of cancer immunotherapy? Lancet Oncol. 2018;19:716-717. doi: 10.1016/S1470-2045(18)30270-5