Dual Neoadjuvant Checkpoint Blockade Feasible in Melanoma

Excerpt:

“Combination neoadjuvant immune checkpoint blockade therapy yielded promising outcomes in high-risk resectable melanoma, although toxicity was an issue, according to a phase II trial.

“The combination of ipilimumab (Yervoy) and nivolumab (Opdivo) led to improved progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS) versus neoadjuvant nivolumab monotherapy in 23 patients with high-risk resectable melanoma, reported Jennifer A. Wargo, MD, of MD Anderson Cancer Center in Houston, and colleagues in Nature Medicine.”

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Predicting If an Immune Checkpoint Drug Will Work


Drugs that activate the immune system to attack cancer in a process known as immune checkpoint blockade (ICB) are a focus of intense investigation. A number of them are already approved by the U.S. Food and Drug Administration (FDA) for various cancers; namely, the anti-CTLA4 antibody ipilimumab (Yervoy), two anti-PD-1 antibodies: pembrolizumab (Keytruda) and nivolumab (Opdivo), and three anti-PD-L1 drugs: atezolizumab (Tecentriq), avelumab (Bavencio) and durvalumab (Imfinzi). These ICB drugs have the potential to induce durable cancer regressions, but the majority of cancer patients just do not respond to them at all.

Biomarkers, signature molecules in the blood or other tissue, can sometimes be used to predict a patient’s response to a given treatment. But no reliable biomarkers exist for ICB, and this is a serious concern. Patients who may really benefit from ICB could be overlooked, and patients who are not likely to respond may receive useless (and very expensive) ICB treatment.

Most potential response predictors that have already been identified are not yet useful for one or all of the following reasons: they are not extensively validated, their significance is still uncertain and may differ from one cancer (or even one patient) to another, or they are technically challenging for routine use. These markers are addressed below. Continue reading…


A Gut Feeling: Bacteria in Your Gut May Affect Cancer Treatment


The human gut contains hundreds of species bacteria, which are known to contribute to various bodily functions (such as digestion, of course!) but they also shape our immune system. Now, recent research has revealed how our microbiomes (the abundant bacteria living in our bodies) may affect the efficacy of immune checkpoint blockade (ICB) in cancer treatment.

How it started: about two years ago, an American group of scientists led by Thomas Gajewski of the University of Chicago noticed that melanoma (and some other cancers’) growth in mice was influenced heavily by the type of bacteria found in the mouse gut. They worked with mice purchased from two different vendors, and realized that mice from one vendor had consistently slower-growing tumors. Bifidobacterium bacteria present in the mouse gut were pinpointed to be the culprit, because transfer of Bifidobacterium to mice that did not have it was able to slow down melanoma growth. Treatment with an immune anti-PD-L1 drug was effective in mice that had the bacteria, but not in mice lacking it. Continue reading…


Immune Checkpoint Agents Advance in Breast Cancer

Excerpt:

“With the prospect of phase III data that could confirm their efficacy, checkpoint inhibitors against PD-1 and PD-L1 have shown promise, both as monotherapies and in combination with chemotherapy for patients with triple-negative breast cancer (TNBC), Sylvia Adams, MD, said during a presentation at the 16th Annual International Congress on the Future of Breast Cancer East.

” ‘We think there is definitely value for immune checkpoint blockade in triple-negative disease. When you look at the metastatic trials, while the response rates are relatively low, most of the responses are durable,’ said Adams, from the NYU Langone Medical Center. ‘For patient selection, it is important to consider the line of therapy. The earlier the better.’ ”

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Nab-Paclitaxel Paired With Anti-PD-L1 Immunotherapies in TNBC Studies

Excerpt:

“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.”

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If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our ASK Cancer Commons service.


Melanoma: New Drugs and New Challenges (Part 1 of 2)


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…


Putting Immune Checkpoint Blockade to the Test in Breast Cancer


About 10 months ago, we asked: Is There a Future for Immunotherapy in Breast Cancer? Now, we can answer this question with a qualified “yes.” The data show why:

Triple-negative breast cancer (TNBC)

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.

Continue reading…


To PD-L1 or Not to PD-L1: That Is the Question


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…


What Determines Whether a Melanoma Patient Will Respond to Checkpoint Blockade Drugs?


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…