The American Society of Clinical Oncology (ASCO) meeting of 2016 is behind us, but oncologists, patients, and journalists are still analyzing the most interesting presentations made there. Below, we describe some of the more prominent results in triple negative breast cancer (TNBC), both promising and disappointing.
Researchers are testing a drug known as IMMU-132 (sacituzumab govitecan) in patients with a variety of cancers. This drug is an antibody-drug conjugate, which means that its molecules contain two parts. One is an antibody that binds to a protein called TROP-2, which is found on the surface of cancer cells, but rarely on normal cells. The antibody part of IMMU-132 is linked to the second part: an anti-cancer drug called SN-38 (the active form of the chemotherapy drug irinotecan). When IMMU-132 binds to cancer cells via TROP-2, it is absorbed by them. But normal cells that do not have TROP-2 on their surface are unlikely to bind IMMU-132 and absorb the drug. TROP-2 is found on the majority of TNBC cells, making it an attractive drug target. Because IMMU-132 does not bind to normal cells, it could potentially reduce the side effects commonly associated with chemotherapy.
At the ASCO meeting, researchers planned to present the results of a phase I/II clinical trial of IMMU-132 in 62 patients with metastatic TNBC who had already received multiple lines of treatment (five prior treatments, on average). The objective response rate (ORR) was 33%, with a median progression-free survival of 5.6 months, and a median overall survival of 14.3 months. Most patients experienced disease stabilization. The most common adverse effects, observed in more than 20% of patients, were decreased neutrophil count, diarrhea, nausea, and vomiting. Based on these results, the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation to IMMU-132 for the treatment of patients with TNBC following at least two previous treatments for metastatic disease. This designation grants IMMU-132 priority review by the FDA. A pivotal phase III trial in metastatic TNBC is expected to launch in the second half of 2016.
Ironically, the presentation of this promising IMMU-132 data at the ASCO meeting did not actually take place. It was literally “kicked out” of the meeting because Immunomedics, the company behind the drug, had previously released the data at an industry working meeting in April, and ASCO meetings prohibit “old,” previously presented data. Well, clearly, the old news still made it into the current news.
Another notable report from the ASCO meeting described the efficacy of the immunotherapy drug atezolizumab (Tecentriq) combined with paclitaxel. Atezolizumab is an immune checkpoint antibody drug that binds to the protein PD-L1, which is sometimes found on cancer cells. PD-L1 on a cancer cell can bind to another protein (PD-1) found on the immune system’s T cells, signaling the T cells not to attack the cancer cells. By binding to PD-L1, atezolizumab prevents the binding of PD-L1 with PD-1, allowing activated T cells to kill cancer cells.
A phase Ib study evaluated the safety and activity of atezolizumab with docetaxel in 32 patients with metastatic TNBC who had already been treated with three or more lines of therapy. The patients were treated with this drug combination for four weeks, followed by atezolizumab alone as a maintenance drug. Among the 24 patients that were evaluable for clinical activity, the ORR was 42%. Responses occurred in patients regardless of how much PD-L1 was found on the surface of their cancer cells; this result was intriguing because the researchers expected that cancer cells with high levels of PD-L1 would be more susceptible to the drug. The most common treatment-related adverse effect was decreased neutrophil count. Notably, patients who had not yet received treatment prior to enrollment in this trial had a 67% response rate—much better than the 25% response rate in patients who received the drugs as a second-line treatment.
Based on the high activity observed in newly diagnosed patients, a phase III, randomized, double-blind, placebo-controlled trial of atezolizumab with paclitaxel for first-line treatment of patients with metastatic TNBC is already ongoing. This trial, IMpassion130 (NCT02425891), will enroll 900 patients with previously untreated TNBC in over 270 sites around the world.
Napabucasin (BBI608) is a promising drug from the class of the so-called “cancer stemness inhibitors” that was reported at the ASCO meeting to have a good activity in gastrointestinal cancers. It inhibits a protein called STAT3, which has been shown to promote the self-renewal (proliferation) of cancer stem cells. Napabucasin was combined with paclitaxel in a phase Ib study that enrolled 35 patients with metastatic TNBC whose cancer had progressed on prior systemic therapies (an average of four prior treatments). Most of these patients had already received a taxane drug (paclitaxel or docetaxel) prior to enrollment. The napabucasin/paclitaxel combo was tolerated well. For the thirty-one patients who could be evaluated for clinical activity, the ORR was 13%. This low number is far from encouraging, which is reflected by the fact that no further clinical testing is planned for napabucasin in TNBC.
In recent years, a treatment strategy called androgen deprivation was thought to be promising in TNBC tumors that have a protein known as the androgen receptor (about 25–30% of TNBC tumors). However, so far, treatment with androgen deprivation drugs used for prostate cancer has produced modest results in TNBC, and there were no new reports on the activity of this class of drugs at the 2016 ASCO meeting. Nonetheless, a new trial was announced that combines the anti-androgen drug bicalutamide with palbociclib, a drug that is FDA-approved for estrogen receptor (ER)-positive breast cancers in combination with anti-estrogen drugs. The known efficacy of palbociclib combined with hormone suppression was no doubt the logic behind the opening of this trial (NCT02605486) for TNBC patients whose tumors have the androgen receptor.