Treatments that unleash the immune system against cancer have been a hot topic for the last few years, but they do not appear in our recent feature on breast cancer for Winship Cancer Institute’s magazine.
Partly, that’s because decent avenues for treatment exist for most types of breast cancer, with improvements in survival since the 1980s. Immunotherapy’s successes have been more dramatic for types of cancer against which progress had been otherwise meager, such as lung cancers and metastatic melanoma.
However, for “triple-negative” breast cancer (TNBC) in particular, immunotherapy could be a good match, because of the scarcity of targeted treatments and because TNBC’s genomic instability may be well-suited to immunotherapy.
Winship oncologists Jane Meisel and Keerthi Gogineni inform Lab Land that several early-phase clinical studies open to breast cancer patients, testing “checkpoint inhibitor” agents such as PD-1 inhibitors, are underway. More are pending.
Meisel’s presentation at Winship’s Sea Island retreat says that immunotherapy is “not yet ready for prime time, but a very promising experimental approach for a subset of patients for whom current therapies are not sufficient. We need to better understand which subsets of patients are most likely to benefit, and how we can use other therapies to enhance efficacy in patients who don’t initially respond.”
TNBCs, especially the BRCA-mutant/basal type, are known to have deficiencies in DNA repair. That provides openings for PARP inhibitors, an example of which, veliparib, is mentioned in the magazine article. This feature of TNBCs could also point toward immunotherapies, which tend to be more effective when there are more mutations and thus more antigens for T cells to attack.
In her presentation, Meisel reviewed the “Keynote 012” study, which tested the PD-1 inhibitor pembrolizumab against several advanced cancer types. Please note the overall response rate for TNBC of just 18.5 percent. One patient had a complete response – possibly an “exceptional responder” — and four had a partial response.
The rest of her presentation is worth a look; it discusses checkpoint inhibitors’ distinctive spectrum of immune-related side effects (skin, gastrointestinal, liver, other inflammation) and unique pattern of responses. Doctors can “consider this approach for patients with good performance status who are running out of chemo options,” Meisel concludes.
A follow-up “Keynote 086” study testing pembrolizumab for metastatic TNBC is underway at Winship now. Keynote 355, combining pembrolizumab with chemotherapy, is planned to start in December, and another study combining PARP inhibitors with a checkpoint inhibitor is also in the pipeline, Gogineni says.
In addition, studies combining checkpoint inhibitors with other agents are underway at Winship. These studies are open to patients with other types of tumors as well and are not specifically labeled for breast cancer. Examples:
CPI-444-001: Atezolizumab + CPI-444, an adenosine receptor blocker to de-repress T cell activity
CA-017-003: nivolumab + BMS-986205, an inhibitor of IDO1, also a T cell regulator
BBI608 — Stat3/”cancer stemness” inhibitor + checkpoint inhibitor