“Only 1 treatment option is currently available for treating patients with metastatic germline BRCA-mutated triple-negative breast cancer (TNBC), but research into novel therapies, including PI3K/conjugates (ADCs) could soon result in a host of new therapies for this hard-to-treat disease.
” ‘Right now, for TNBC, chemotherapy is our only option,’ said Joyce A. O’Shaughnessy, MD, co-chair of Breast Cancer Research and the chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center and for The US Oncology Network. ‘That’s about to change very soon with the likely availability of atezolizumab [Tecentriq].’ ”
“Developing predictive biomarkers will be key to treating patients with triple-negative breast cancer (TNBC), especially when choosing a targeted therapy, said Banu K. Arun, MD.
“In a presentation during the 2018 OncLive® State of the Science Summit™ on Breast Cancer, Arun said there is evidence that PARP inhibitors as well as immunotherapy in combination with various agents may be effective in women with TNBC and BRCA1-related breast cancers, but the science isn’t there yet.”
“First-line atezolizumab plus nab-paclitaxel improved PFS compared with placebo among patients with metastatic or unresectable locally advanced triple-negative breast cancer, according to interim results from the IMpassion130 trial released by the manufacturer.
“Researchers observed prolonged PFS in both the intention-to-treat population and the PD-L1-positive population.”
“Half of patients with metastatic triple-negative breast cancer (TNBC) achieved disease control when treated with the combination of a poly (ADP-ribose) polymerase (PARP) inhibitor and an anti–PD-1 agent, a preliminary prospective study showed.
“Overall, 13 of 46 evaluable patients had objective responses to treatment with niraparib (Zejula) and pembrolizumab (Keytruda). An additional 10 patients had stable disease. Clinical activity was observed in patients beyond those with germline BRCA mutations.”
“Enzalutamide (Xtandi) demonstrated early signs of efficacy in patients with androgen receptor (AR)-positive triple-negative breast cancer (TNBC), according to findings from the phase II MDV3100-11 study published in the Journal of Clinical Oncology.
“A total of 118 patients were enrolled in the single-arm, 2-stage trial, and 78 were evaluable for response. At 16 weeks, the clinical benefit rate (CBR) was 25% (95% CI, 17-33) in the intent-to-treat (ITT) population and 33% (95% CI, 23-45) in the evaluable subgroup. The median progression-free survival (PFS) was 2.9 months (95% CI, 1.9-3.7) in the ITT population and 3.3 months (95% CI, 1.9-4.1) in the evaluable subgroup. Median overall survival (OS) was 12.7 months (95% CI, 8.5 – not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 – not yet reached) in the evaluable subgroup.”
“Updated results of the phase Ib/II ENHANCE1/KEYNOTE-150 study presented at the 2017 San Antonio Breast Cancer Symposium found that the combination of pembrolizumab (Keytruda) and eribulin (Halaven) was associated with a 26.4% objective response rate (ORR) for patients with metastatic triple-negative breast cancer (TNBC).
“In the open-label study, the ORR with the combination for untreated patients with metastatic TNBC (n = 65) was 29.2% (95% CI, 18.6%-41.8%). In a cohort of patients pretreated with 1 to 2 therapies (n = 41), the ORR was 22.0% (95% CI, 10.6%-37.6%). Across all treatment arms, there were 3 complete responses to the combination (2.8%).”
“Treatment with nab-paclitaxel (Abraxane) showed promising improvements in overall survival (OS) and progression-free survival (PFS) compared with standard paclitaxel for patients with metastatic triple-negative breast cancer (TNBC), according to post-hoc findings from the CALGB 40502/NCCTG N063H trial presented at the 2017 San Antonio Breast Cancer Symposium (SABCS).
“For those with TNBC in the phase III trial (n = 201), the median OS with nab-paclitaxel was 21.0 months compared with 15.3 months with standard paclitaxel, representing a 26% reduction in the risk of death. Given the limitations of the post-hoc assessment, these findings were not powered for statistical significance, explained lead investigator Hope S. Rugo, MD. The hazard ratio for the comparison was 0.74 (95% CI, 0.51-1.07).”
“Treatment with IMMU-132 (sacituzumab govitecan) elicited an objective response rate (ORR) of 34 percent in patients with heavily pretreated metastatic triple-negative breast cancer, according to updated findings from a phase 2 study presented at the 2017 San Antonio Breast Cancer Symposium (SABCS).
“In the 110-patient single-arm trial, the ORR was accompanied by stable disease (SD) for 6 months or more in 11 percent of patients, for an overall disease control rate of 45 percent. The median progression-free survival (PFS) with IMMU-132 was 5.5 months and the median overall survival (OS) was 12.7 months.”
Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.
Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.
However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.
In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…