While we are still working on figuring out the mechanisms underlying differences in the lung cancers of women vs. men, the efficacy and survival paint a consistent picture that women with lung cancer live longer than men regardless of the lung cancer subtype, stage, or treatment used (summary here). Large studies have reported that women have an approximately 15-20% improvement in survival, controlling for other variables, when compared to men. Women appear to have a superior survival in surgical trials (abstract here) and also trials with chemo and radiation (abstract here). Although there are some trials in which significant differences are not seen, we don’t see trials in which do better than women with lung cancer.

Turning to sex differences in response to chemo, you can see from a few trials that women typically have a median survival that is 1-2, and in some studies 3-4 months, better than their male counterparts:

(click to enlarge)

The last trial on this slide, ECOG 4599 (abstract here), which tested avastin in combination with carboplatin/taxol, is quite interesting, In this trial, women did remarkably better than men, particularly if the men didn’t receive avastin (13.1 vs. 8.7 months: quite a difference). The women who received Avastin didn’t fare better than women who received carbo/taxol alone, but the women on both arms did remarkably well, over 13 months. We’ll cover the issue of women and avastin in a separate post very soon.

In the meantime, the studies that break down survival for women vs. men and show markedly better survival in women also shown significantly higher toxicity in women. The specific problems more commonly seen in women vs. on chemo included worse nausea, vomiting, neuropathy, and sometimes more hair loss and neuropsychiatric side effects.

I already mentioned in a prior post that the “next generation” taxane Xyotax (paclitaxel polyglumex) did not pan out as showing significant benefits overall compared to other chemo agents, but it did emerge as superior in an analysis just of women. Although the PIONEER study of marginal performance status women closed, for reasons that have not been well described but apparently did not look as favorable for the women on Xyotax, the company that makes Xyotax (Cell Therapeutics, Inc.) is launching a different phase III trial, PGT-307, that will focus on women with pre-menopausal estrogen levels only. The basis of the focus on women for Xyotax is that the biodegradable polymer to which paclitaxel is bound to make Xyotax (poly-L-glutamic acid) is broken down to its active metabolite form by an enzyme called cathepsin B, which is modulated by estrogen. So Xyotax is actually being developed as the first sex-specific lung cancer drug.

We’ll turn to EGFR-based therapies next.