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…
“Atezolizumab (Tecentriq) monotherapy produced substantial response rates as first-line or subsequent treatment in patients who had advanced non-small cell lung cancer (NSCLC) with confirmed programmed cell death ligand 1(PD-L1) expression, reported the phase II BIRCH trial.
“Atezolizumab therapy produced a 22% objective response rate in first-line treatment, 19% in second-line, and 18% in third-line or higher in patients with PD-L1 expression on ≥ 5% of tumor cells (TC) or tumor-infiltrating immune cells (IC), according to Enriqueta Felip, MD, PhD, of Vall d’Hebron University Hospital in Barcelona, Spain, and colleagues. Patients with the highest levels of PD-L1 expression — TC3 or IC3 — had better objective response rates: 31% in first-line, 26% in second-line, and 27% third-line or higher.”
“According to the results of a phase I study of single agent anti-PD-L1 atezolizumab (Tecentriq) in metastatic triple-negative breast cancer (mTNBC), ten percent of patients showed impressive long-term survival, although researchers said that aside from some biomarker evidence, it’s yet unclear why the drug was more effective in this subset of patients.
“Results of the study were presented this week at the AACR Annual Meeting 2017 by lead author Peter Schmid, MD, PhD, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London.”
“Among patients with metastatic triple-negative breast cancer (TNBC) who were treated with the anti-PD-L1 cancer immunotherapy atezolizumab (Tecentriq), those who responded to the medicine lived significantly longer (overall survival) compared with those who did not respond, according to data from a phase I clinical trial presented here at the AACR Annual Meeting 2017, April 1-5.
” ‘Triple-negative breast cancer is an aggressive subtype of breast cancer often affecting younger women and, unfortunately, the current treatment options for metastatic disease remain limited,’ said Peter Schmid, MD, PhD, director of the St. Bartholomew’s Breast Centre at St. Bartholomew’s Hospital and Barts Cancer Institute in London.”
By 2050, the number of deaths due to malignant melanoma in the U.S. could be three times lower than peak levels reached before 1960. Researchers presented the data behind this prediction at the 2017 European Cancer Congress in January.
It is unclear how much of this anticipated decline in deaths can be attributed to the availability of new, effective treatments. However, it is obvious that much-increased awareness of sunlight exposure as the single factor most responsible for the development of skin melanoma has contributed to lower incidence of the disease.
In any case, the armament of treatments available for metastatic melanoma is currently such that this diagnosis has transformed from being almost universally fatal (even just a few years ago) into a being largely treatable. Since 2011, the U.S. Food and Drug Administration (FDA) has approved eight new drugs for melanoma. Continue reading…
“In the phase III OAK trial reported in The Lancet by Rittmeyer et al, treatment with the anti–programmed cell death ligand 1 (PD-L1) antibody atezolizumab (Tecentriq) improved overall survival vs docetaxel in previously treated non–small cell lung cancer (NSCLC). Results of the trial supported the recent approval of atezolizumab in metastatic NSCLC in patients who have received prior platinum-containing therapy.”
“Patients with advanced non-small-cell lung cancer survive four months longer with fewer side effects on an immunotherapy drug called atezolizumab compared to chemotherapy, according to a phase 3 clinical trial published in The Lancet.
“The trial enrolled 1225 advanced non-small-cell lung cancer patients who have no more treatment options, but this study used an early analysis of the first 850 patients from the trial. Half of the group were given atezolizumab and the other half were given docetaxel chemotherapy, which is the standard treatment for advanced non-small-cell lung cancer.
“Patients given atezolizumab – a drug that blocks the programmed death ligand 1 (PD-L1) protein – survived for an average of 13.8 months, compared with 9.6 months for those on chemotherapy.”
“G1 Therapeutics, Inc., a clinical-stage oncology company, announced today a clinical trial collaboration with Genentech, a member of the Roche Group. A Phase 2 clinical trial is expected to begin in the first half of 2017 and will evaluate the combination of Genentech’s immune checkpoint, anti-PD-L1 antibody Tecentriq® (atezolizumab) with G1’s CDK4/6 inhibitor trilaciclib (G1T28) as a first-line treatment for patients with small-cell lung cancer (SCLC) receiving chemotherapy.”
“The combination of atezolizumab (Tecentriq) and cobimetinib (Cotellic) may lead to a higher overall response (ORR) and a longer progression-free survival (PFS) than either agent alone in patients with metastatic melanoma, according to findings presented at the 2016 Society for Melanoma Research (SMR) Annual Meeting.
“The findings were part of a phase Ib dose-escalation and dose-expansion study, which looked at the PD-L1 inhibitor and MEK inhibitor together in advanced solid tumors. Data on a cohort of 22 patients with ocular melanoma (n = 2) and non-ocular melanoma (n = 20) was presented at the meeting. Among patients in the non-ocular cohort, the ORR was 45% and the disease-control rate (complete response, partial response, and stable disease) was 75%. Median PFS was 12 months (95% CI, 2.8-16.7).”