Toripalimab shows promise in advanced triple-negative breast cancer | ASCO 2023

Background

Triple-negative breast cancer, or TNBC, does not grow in the presence of estrogen, progesterone, or HER2, and so medicines that target those receptors don't work for it. For many years chemotherapy was the best treatment option for this type of breast cancer.  The past few years have brought new FDA approvals and hope for people living with TNBC. The current standard treatment often involves chemotherapy, immunotherapy, and sometimes targeted therapy.

The immunotherapy drug toripalimab is a monoclonal antibody that targets the protein PD-1 found in immune cells. It is an immune checkpoint inhibitor that works in a similar way to another medicine approved for TNBC.

Toripalimab is the first drug of this kind developed in China, where it is approved to treat melanoma, nasopharyngeal cancer, and urothelial cancer. The drug has FDA fast track and orphan designations for specific cancers in the U.S. but has faced delays in receiving full approval due to the COVID-19 pandemic. In order to approve a drug developed outside of the U.S., the FDA must inspect the manufacturing facilities.

Results

The TORCHLIGHT clinical trial compares toripalimab combined with chemotherapy to chemotherapy alone in metastatic or recurrent TNBC. Early results show significant improvement in progression-free survival in a subgroup of participants who test positive for the PD-L1 immune marker (a combined positive score–CPS–of one or more).

This phase III randomized, double-blind study included 531 people randomized to two groups (or arms)–one that received toripalimab plus nab-paclitaxel (Abraxane) and a second that received placebo, an inactive substance, plus nab-paclitaxel. Participants included people diagnosed with breast cancer at stage IV (de novo) as well as people with recurrent or metastatic breast cancer. Most participants (95%) had not received drug therapy prior to this trial. People remained in the trial until their disease did not respond to treatment or they were unable to tolerate the side effects.

The authors reported results for the entire study group and for the PD-L1+ subgroup. In the entire study group, toripalimab showed a positive trend, but the findings were not statistically significant. In the PD-L1+ group, participants in the toripalimab plus chemotherapy arm went an average of 8.4 months without cancer growth or spread compared to 5.6 months in the chemotherapy-only arm of the trial.

Early data suggest that toripalimab may improve overall survival. Among PD-L1+ participants, people with advanced breast cancer who received toripalimab plus chemotherapy lived for 32.8 months compared to 19.5 months for participants in the chemotherapy-only arm. These numbers were 33.1 months compared to 23.5 months for all participants in the trial. These trends are not statistically significant at this time, meaning they could have happened by chance.

Side effects reported in the trial showed toripalimab to be well tolerated. As expected, participants receiving toripalimab had more immune-related side effects such as changes in blood counts and an increased risk of infection. Other common side effects reported by participants in both arms of the clinical trial included hair loss, nausea, rash, decreased appetite, and constipation.

What does this mean for you?

These results are promising but still early. Toripalimab is being developed and studied in China so it is not yet available, even on clinical trial, in the U.S. If you are interested in immunotherapy for TNBC, ask your doctor about drugs that are approved or being studied in clinical trials.

Notably, toripalimab worked best against advanced breast cancers that test positive for PD-L1 based on a CPS of one or more. This score is lower than the score of 10 required for pembrolizumab (Keytruda), which is already approved by the FDA to treat TNBC. This difference is worth watching and, if these early results hold out, could ultimately result in a broader approval for the new drug.