“Combination regimens that pair nab-paclitaxel (Abraxane) with PD-L1 checkpoint blockade immunotherapy agents are emerging as a robust area of investigation in triple-negative breast cancer (TNBC), bolstered by clinical trial results that establish the chemotherapeutic agent as an effective partner for other therapies.
“Although nab-paclitaxel has been combined in some studies with other chemotherapies, the focus is shifting to regimens that include immunotherapies as the efficacy of that approach continues to grow. Nab-paclitaxel, an albumin-bound form of paclitaxel, is indicated for patients with metastatic breast cancer after prior chemotherapy.”
New targeted and immunotherapy drugs have changed the diagnosis of metastatic melanoma from a death sentence into a disease that can potentially be managed and even cured. Nevertheless, these new drugs do not work in all patients, or they may stop working after a transient response. This post (part one of two) will describe ongoing efforts to find drug combinations with higher efficacy than single drugs and decipher the mechanisms underlying drug resistance. Continue reading…
TNBC has long been considered to be more amenable to immune system-based treatments than other types of breast cancer because it is more immunogenic; that is, relatively high levels of immune cells accumulate within or adjacent to TNBC tumors. These immune cells could be triggered to attack tumors if properly activated. TNBC tumors are also likely to have a higher mutational burden (number of genetic mutations). This is one of the predictors of sensitivity to a type of treatment called immune checkpoint blockade. Drugs known as checkpoint inhibitors block the proteins PD-1 or PD-L1. In cancer, PD-L1 proteins on tumor cells bind to PD-1 proteins on immune T cells and inhibit their tumor-killing activity. Immune checkpoint drugs disable this interaction and enable activation of T cells. These drugs are actively being explored in TNBC in clinical trials.
These days, it seems that I write mostly about immune checkpoint blockade drugs, or some other new immunotherapy treatment for cancer. This post is no different—it covers PD-L1, a protein that is at the center of clinical decisions for selecting patients who are likely to benefit from treatment with an anti-PD-1 or anti-PD-L1 drug. Continue reading…
Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…
“Spreading the success of cancer immunotherapy beyond those patients currently enjoying powerful, long-term responses to treatment requires greater understanding of the immune response to tumors, two leaders in the field note in a review in the April 3 Science.
” ‘Identifying in advance who will benefit from treatment and developing combination therapies to improve and expand on current results will require us to decipher the dynamics of human immune response to tumors and their surrounding microenvironment,’ said co-author Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology at The University of Texas MD Anderson Cancer Center.
“Immune checkpoint blockade, the unleashing of immune response against cancer by blocking molecules on T cells that shut down those attacking cells, produces durable results and long-term survival in a substantial fraction of patients with some cancers. For example, 22 percent of advanced melanoma patients treated with ipilimumab (Yervoy®), the first checkpoint inhibitor, live for four years or longer. Right now there’s no way to identify those most likely to benefit.
“Lion Biotechnologies, Inc. (Nasdaq: LBIO), a biotechnology company that is developing novel cancer immunotherapies based on tumor infiltrating lymphocytes (TIL), today announced that researchers from Moffitt Cancer Center reported positive results from a pilot trial of TIL and ipilimumab in patients with metastatic melanoma. The data from the trial, which Lion partially sponsored, were presented at the Society of Surgical Oncology 2015 meeting in Houston, TX on Friday, March 27, 2015.
“The Phase 1 trial was conducted at Moffitt Cancer Center in 12 patients with metastatic melanoma, with the objective of determining the safety and feasibility of combining TIL therapy with the CTLA-4 checkpoint inhibitor, ipilimumab. Patients were treated with ipilimumab one week prior to tumor harvest for TIL expansion, a second time while their TIL were being expanded, and two more times following TIL transfer.
“Of the 12 patients enrolled in the trial, 11 went on to receive their autologous TIL, with five out of the 11 TIL-treated patients (46%) responding to treatment (one complete response and four partial responses), consistent with response rates from previous TIL studies in metastatic melanoma. Notably, the researchers observed that following a single infusion of ipilimumab, TIL grew to higher numbers than historically had been observed in previous studies, in which ipilimumab was not administered prior to tumor harvest. In addition, only one of the 12 enrolled patients (8%) was ineligible for TIL transfer, indicating relatively high patient adherence to trial protocol.
” ‘Ipilimumab has potential to enhance the effectiveness of TIL therapy by boosting the concentration of tumor-reactive T cells in the tumors of patients prior to TIL harvest, and by controlling disease before TIL transfer,’ said Sangeetha Prabhakaran, MD, the study’s presenting author. ‘Based on the results of this study, we conclude that TIL-ipilimumab combination treatment is both safe and feasible. Furthermore, this approach serves as a model for future efforts to combine TIL with PD-1/PD-L1 blockade and other emerging immune checkpoint inhibitors.’ “
Lately, immunotherapy—treatment that helps the body’s own immune system fight cancer—has made frequent appearances in news headlines. Indeed, researchers have reported remarkable clinical trial results for a new class of drugs known as ‘immune checkpoint blockade drugs‘ in the treatment of metastatic melanoma, lung, and kidney cancers. Approvals from the U.S. Food and Drug Administration (FDA) for the drugs Keytruda and Opdivo for melanoma and lung cancer have quickly followed. However, it may be that immunotherapies won’t work for all cancers, but only for those considered to be ‘immunogenic’; that is, cancers that trigger activation of the immune system. Researchers are studying different types of breast cancer to determine whether they are immunogenic, and what that might mean for their prognosis and treatments. Continue reading…
“In the summer of 2012, a year after his wife had died of lung cancer, Michael Harris scraped open an old mole on his back and it would not stop bleeding. The doctors said he had stage 4 melanoma, with a virtually inoperable tumor, and that patients in his condition typically lived about eight months. By last June, the cancer had spread to his liver and lungs.
“At that point Harris joined a clinical trial at Georgetown University, one of scores that have sprung up around the country to test a new class of cancer drugs called immune-checkpoint inhibitors. Two weeks after his first infusion, Harris’s primary tumor was fading, along with the black cancerous beads around it. A month later, his liver and lungs were clean.”