While there are currently no approved active immunotherapies for the breast, ovarian, and gynecological cancers that predominantly affect women, several approaches highlighted at ASCO 2016 provide hope that these might soon become available. In addition, several talks focused on smarter strategies aimed at improving outcomes in women with these cancers.
Atezolizumab, an anti-PD-L1 checkpoint antibody that has already been approved for bladder cancer, may be one way to better treat patients with the hard-to-treat triple-negative breast cancer (TNBC). As Sylvia Adams, M.D., of the NYU Langone Medical Center showed, when combined with chemotherapy, atezolizumab therapy led to responses in 38% of TNBC patients, while another 44% experienced stabilization of their disease.
Another option could be the combination of durvalumab, another anti-PD-L1 checkpoint antibody, and olaparib, which inhibits the PARP pathway that many cancer cells depend on. Jung Min Lee, M.D., of the National Cancer Institute’s Center for Cancer Research, revealed that this combination is safe and also appears to promote clinical activity in patients with TNBC as well as ovarian cancer (OC). Ongoing efficacy analysis will hopefully highlight positive responses in these patients.
In addition to checkpoint immunotherapy, the CAR T cell technology responsible for amazing breakthroughs in blood cancer patients may also be able to help patients with OC. Janos Laszlo Tanyi, M.D., of the University of Pennsylvania revealed that CAR T cells engineered to attack cancer cells expressing mesothelin were able to engraft and expand within patients. Importantly, these anti-mesothelin CAR T cells also infiltrated into multiple tumor sites. While only six patients have been treated thus far, all six have experienced disease stabilization at least 28 days after treatment. Further monitoring will be necessary to determine this approach’s long-term durability.
Even in patients that receive non-immunotherapy treatments, immune cells appear to play an important role in survival. Anosheh Afghahi, M.D., of Stanford Medicine, showed that TNBC patients with higher numbers of immune cells in their peripheral blood had higher 5-year overall survival, and furthermore, that this correlation increased over time.
Several talks also discussed smarter strategies to ensure that patients are treated with the appropriate therapies, including immunotherapy, and this is especially important for patients with rare gynecological cancers. Although no one type represents a significant fraction of gynecological malignancies, collectively, the more than 30 subtypes make up over half of all cases. To improve doctors’ ability to treat this wide diversity, Victor Rodriguez Freixinos, M.D., of the Vall d'Hebron University Hospital spoke of the advantages of analyzing these tumors to identify actionable alterations, and added that a better understanding of tumor biology may suggest the most potentially effective treatments for specific patients. Already, trials that have incorporated this type of analysis to select patients increased the amount of time patients go without progression after treatment, compared to trials that don’t take individual tumor properties into account.
Finally, Allison Kurian, M.D., M.Sc., of Stanford Medicine spoke about how genetic mutations contribute to ovarian cancer risk. Specifically, she highlighted 11 genes that have been shown to increase—between 2-fold and 40-fold—a person’s risk of developing ovarian cancer. However, she also noted that these mutations offer opportunities to develop tumor-specific treatments that target these abnormalities.