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 inhibitors have significantly reshaped the treatment landscape of advanced non-small cell lung cancer (NSCLC) in the second-line and, more recently, in the first-line setting. However, only a subset of patients achieves a durable response on immunotherapy, and it is not clear whether prior immunotherapy treatment impacts response to salvage chemotherapy.
“A recent retrospective study evaluated responses to salvage chemotherapy in 73 patients with advanced NSCLC who had progressed on prior PD-1/PD-L1 inhibitors. Ten of the 73 patients had received immunotherapy as first-line treatment, while the remaining 63 patients had received immunotherapy as second-line treatment following first-line chemotherapy. Response to salvage chemotherapy was compared to response to the last chemotherapy administered before immunotherapy (LCBI).”
“In a first-of-its-kind study, University of California San Diego School of Medicine researchers report that a blood sample, or liquid biopsy, can reveal which patients will respond to checkpoint inhibitor-based immunotherapies.
” ‘We can help predict response to immunotherapy by measuring the number of mutations in circulating tumor DNA using a simple blood test,’ said Yulian Khagi, MD, UC San Diego Moores Cancer Center fellow and first author. ‘Immunotherapy can result in serious side effects, and therefore being able to predict who will respond is important to mitigating potential risk to each patient.’ ”
“The combination of stereotactic ablative radiotherapy plus anti-PD-1 therapy improved survival among patients with advanced lung cancer, according to a retrospective analysis presented at the International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.
“Immune checkpoint inhibitors have improved outcomes in non-small cell lung cancer. However, the absolute improvement over docetaxel is only 3 to 5 months for median OS and 15% to 20% for overall response rate.”
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…
“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.’ ”
There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…
“Seasonal influenza vaccination resulted in increased risk of immune-related adverse events (AEs) in lung cancer patients treated with PD-1/PD-L1 checkpoint inhibitors in a small study. However, the risks of the flu itself may still outweigh the risks associated with vaccination.
” ‘Use of immune checkpoint inhibitors is now standard clinical practice for many oncology patients, and these same patients—particularly those with lung cancer—also face increased risk for complications from influenza,’ said Sacha Rothschild, MD, PhD, of University Hospital Basel in Switzerland, in a press release. ‘Although routine influenza vaccination has long been recommended for cancer patients, there are concerns that it might trigger an exaggerated immune response in this subgroup receiving checkpoint inhibitors.’ ”
“White blood cell counts can predict whether or not lung cancer patients will benefit from immunotherapy, according to research presented at the European Lung Cancer Conference (ELCC).
” ‘Immune checkpoint inhibitors such as nivolumab and pembrolizumab significantly improve overall survival in some – but not all – patients with non-small cell lung cancer (NSCLC),’ said lead author Dr Marcello Tiseo, Coordinator of DMT Thoracic Oncology, University Hospital of Parma, Italy. ‘Researchers are looking for a predictive biomarker to select patients that will benefit from this treatment to avoid unnecessary toxicity and a waste of resources in patients who will not respond.’ ”