“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.”
“Half of patients with melanoma who progressed on anti–PD-1/PD-L1 therapy benefited from the combination of nivolumab (Opdivo) and the LAG-3 inhibitor relatlimab (BMS-986016), data from a dose-expansion study showed.
“The combination led to objective responses in 7 of 61 evaluable patients, increasing to 18% in a subgroup of patients LAG-3–positive tumors. Half of all patients treated and two-thirds of those patients with LAG-3–positive tumors derived clinical benefit, as reported at the 2017 ESMO Congress.”
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.’ ”
“Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco researchers joined by physicians from UCSF Health. The findings provide a novel predictive biomarker to identify patients who are most likely to respond well to a combination of immunotherapy drugs known as checkpoint inhibitors—and to protect those who won’t respond from potentially adverse side effects of combination treatment.
” ‘Combination immunotherapy is super-expensive and very toxic,’ said Adil Daud, MD, director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center and senior author of the new study. ‘You’re putting patients at a lot of extra risk if they don’t need it, and you can adjust for that risk by knowing in advance who can benefit.’ ”
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…
“Patients with melanoma continued to experience tumor response to nivolumab monotherapy when treated beyond progression, according to a pooled analysis of data from the CheckMate 066 and CheckMate 067 studies.
” ‘The results of this analysis suggest that continued treatment with nivolumab [Opdivo, Bristol-Myers Squibb] may be an option to achieve further apparent clinical benefit in some patients with advanced melanoma,’ Georgina V. Long, PhD, BSc, MBBS, FRACP, chair of melanoma medical oncology and translational research at Melanoma Institute Australia and Royal North Shore Hospital of The University of Sydney in Sydney, Australia, and colleagues wrote.”
“Immunotherapy may represent an effective new treatment approach for relapsed mesothelioma patients, according to a new study.
“Anti–programmed death-1 (PD-1) immunotherapy may have activity as second- or third-line therapy in malignant pleural mesothelioma (MPM), an aggressive, rare cancer associated with asbestos exposure that has no curative treatment. All MPM patients relapse despite initial chemotherapy, and median overall survival (OS) is 9 months at most, said lead author Arnaud Scherpereel, MD, PhD, head of the pulmonary and thoracic oncology department at the University Hospital (CHU) of Lille in Lille, France, at a press briefing at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract LBA8507).”
“Nivolumab plus ipilimumab demonstrated an intracranial response (ICR) rate of 42% in asymptomatic patients with melanoma brain metastases who had not received prior local therapy to the brain.
“In the phase II Anti-PD1 Brain Collaboration (ABC) trial, the 6-month intracranial PFS rate was 46% with the anti–PD-1/CTLA-4 combination.
” ‘The combination of nivolumab and ipilimumab has high activity in melanoma brain metastases and may be considered for upfront therapy in such patients,’ said lead author Georgina V. Long, BSc, PhD, MBBS, clinical researcher at the Melanoma Institute Australia and Westmead Hospital in Sydney.”