Last month, the annual American Society of Clinical Oncology (ASCO) meeting took place in Chicago. Thousands of oncologists, patients, and journalists gathered to learn about the most recent developments in cancer research and treatment. Here are some breast cancer highlights from the meeting:
Triple negative breast cancer (TNBC) is considered more responsive to treatment with immune checkpoint drugs than any other type of breast cancer. So far, these drugs have primarily been explored in metastatic TNBC, in combination with chemotherapy. The combination of “anti-PD-L1” and “anti-PD-1” immune checkpoint drugs with chemotherapy has now been examined in early-stage TNBC, in which a breast tumor can be surgically removed after neoadjuvant chemotherapy.
The clinical trial results show that addition of the immune checkpoint drug durvalumab (anti-PD-L1) to chemotherapy (weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide, or “ddAC”) increases the rate of pathologic compete responses (pCR; when a tumor is no longer detectable). Preliminary results of a tiny trial with only seven women reported 71% pCR; i.e., pCR in five of the seven women, which compares favorably to the historical rate of 35–40% pCR with chemotherapy alone.
Results from the I-SPY2 trial showed that addition of the anti-PD-1 drug pembrolizumab (brand name Keytruda) to standard chemotherapy increased the pCR rate to 60% in patients with TNBC. These data are important, as the rates of TNBC recurrence after surgery are high, and attaining pCR bodes well for prognosis. As always, more studies are needed.
Cancers with BRCA1/2 mutations: These mutations are found in about 3% of breast cancers, mostly in TNBC. PARP-1 inhibitor drugs are candidates for treating BRCA-mutant cancers of all types, but promising results in breast cancer have not been forthcoming. In a phase III randomized clinical trial, olaparib, a PARP inhibitor already approved by the U.S. Food and Drug Administration (FDA) to treat ovarian cancer with BRCA mutations, showed a higher overall response rate (ORR) than chemotherapy (60% vs. 29%), a longer time to progression (7 months vs. 4.2 months) and fewer side effects. Unfortunately, this trial used chemotherapy without platinum-based drugs as a comparator treatment (platinum drugs are more effective against tumors with BRCA mutations than the chemotherapy drugs used in this trial). These results were presented at the ASCO meeting and simultaneously published in a prestigious medical journal.
Another PARP inhibitor, talazoparib, also showed somewhat promising activity in a phase II trial that enrolled heavily pretreated patients. The ORR in patients who had previously received a platinum drug was 21%, and in patients who had received at least three previous treatments (without a platinum drug), the ORR was 37%. Talazoparib is now moving to a phase III trial.
HER2-positive breast cancer: A setback for pertuzumab (brand name Perjeta) was notable at ASCO 2017, even though the reporting was not negative. Pertuzumab is an anti-HER2 antibody drug that is FDA-approved together with trastuzumab (Herceptin) and chemotherapy (in the “THP” regimen) for neoadjuvant (pre-surgery) treatment of HER2+ breast cancer and for treatment of metastatic disease. A large study called APHINITY explored whether THP after surgery (adjuvant treatment) for early HER2+ breast cancer can lower the risk of recurrence. This was an obvious effort by Perjeta manufacturer Roche to expand the indications for the drug. The three-year rates of disease-free survival were 94.1% in the group of patients receiving pertuzumab and 93.2% in the placebo group—not exactly an exciting difference by any count. Still, the study was presented with a positive spin and published in a prestigious journal. It has also attracted a lot of criticism citing the really tiny effect of pertuzumab in reducing the risk of recurrence and an increase in potentially serious side effects.
Another trial, MARIANNE, explored whether the drug T-DM1, alone or with pertuzumab, works better than the older, standard treatment in metastatic cancer; trastuzumab with taxane chemotherapy (the current guidelines recommend taxane, trastuzumab, and pertuzumab—THP—as the first line of treatment). T-DM1 is currently FDA-approved for patients in whom THP has stopped working; i.e., as a second-line treatment. The answer from this large trial with over 1,000 patients was a qualified “NO” to the use of T-DM-1 in first-line metastatic cancer treatment. The overall response rates were pretty close in the three treatment groups, and so were the progression-free survival rates. The only criterion by which T-DM1 was superior was the median duration of response to TDM-1 (or TDM-1 with pertuzumab), which was around 20–21 months versus 12.5 months in the trastuzumab group. This is not enough to change the current treatment guidelines.
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