Checkpoint Inhibitor Drugs Targeting Pd
Programmed cell-death 1 is a glycoprotein normally expressed by macrophages and T-cells. The binding of PD-1 to its ligands inhibits cytotoxic T-cell immune response and leads to an immune escape of the cells that express these ligands. These may be constitutively present on tumor cells, in particular it was found in up to 6590% of ATC cells . Preclinical studies demonstrated that PD-1/PD-L1 blockade was effective in reducing tumor growth and, when anti-PD-1/PD-L1 antibody was administered in combination with a BRAF-inhibitor, it reduced tumor volume and prolonged survival in murine models . Furthermore, in vivo study showed that inhibition of PD-1/PD-L1 pathway enhances Lenvatinib anti-tumor activity, through modification of ATC microenvironment . A phase II clinical trial evaluated efficacy and tolerability of Spartalizumab in 42 ATC patients. Spartalizumab was administered at a dosage of 400 mg intravenous every 4 weeks. ORR and DCR were 19% and 31% median PFS and OS were 1.7 and 5.9 months, respectively. In the subgroup of patients with PD-L1 expression, ORR was 29%, and it was even higher when only patients with strong intensity PD-L1 expression were analyzed. These results were independent from the BRAF mutational status. AEs occurred in almost all patients, the most frequent being diarrhea, pruritus, fatigue, and pyrexia . In conclusion, Spartalizumab proved to be a valid therapeutic option in patients with PD-L1-positive advanced ATC.
Rectal Cancer Disappears After Experimental Use Of Immunotherapy
A small but historic trial led by MSK medical oncologist Andrea Cercek, MD, and medical oncologist Luis Diaz, Jr., MD, found that for patients with certain gene mutations, immunotherapy completely eliminated their rectal cancer, enabling them to avoid debilitating side effects from the standard treatment of radiation, surgery, and chemotherapy. After more than two years, all 14 patients in the trial remained cancer free. The checkpoint inhibitor drug dostarlimab was given to patients with stage 2 or 3 rectal cancer whose tumors were classified as mismatch repair-deficient or microsatellite instability . Results from the trial were presented at the American Society of Clinical Oncology meeting on June 5, 2022, and published in The New England Journal of Medicine the same day.
Risk Stratification Molecular Testing Among Recent Advances In Thyroid Cancer Treatment
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During the past 2 decades, Endocrine Today has reported on the latest developments in treating thyroid cancer. For its 20thyear, the publication is taking a look back.
Twenty years ago, the options for treating differentiated thyroid cancer were much more limited than they are today.
When differentiated thyroid cancer was diagnosed 2 decades ago, most patients underwent a total thyroidectomy followed by radioactive iodine, regardless of the characteristics of the thyroid tumor or the patient.
Elizabeth H. Holt
In the past, pretty routinely once we had a biopsy that came back indicative of cancer or looking like it could be a cancer, very often those patients would get the entire thyroid taken out,Elizabeth H. Holt, MD, PhD, associate professor of endocrinology at Yale School of Medicine, told Healio.
Today, the treatment of thyroid cancer has been significantly altered. Advances in ultrasound neck mapping and molecular testing, in addition to updated risk stratification guidelines published by the American Thyroid Association in 2015, allow providers to take a more individual approach to managing thyroid cancer. This has led to less aggressive treatment for people with low-risk cancers.
Having access to a high-volume, experienced thyroid surgeon is critically important for the care of thyroid cancer patients, Pearce told Healio.
Arti Bhan
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Medullary Thyroid Cancer Treatment
A rare type of thyroid cancer called medullary thyroid cancer begins in the thyroid cells that produce a hormone called calcitonin. Radioactive iodine is not effective for these cancers. Targeted therapies such as vandetanib and cabozantinib may be used if the disease recurs after surgery or if it has spread elsewhere in the body . Researchers are looking for better drugs for the treatment of medullary thyroid cancer:
A Collaborative Approach And An Emphasis On The Surgical Safety Profile
A multidisciplinary endocrine clinic has been established with the support of Dr. Patrick Byrne, Chair of the Head & Neck Institute, Cleveland Clinic Foundation along with Christian Nasr, MD, and . This affords us the opportunity to have direct interactions beyond both our standard head and neck tumor board and our separate multidisciplinary thyroid cancer tumor board to treat complex patients. Although guideline development can be difficult for these more uncommon tumors,2 we have been instrumental in contributing to an American Head and Neck Society Consensus Statement.3 Our multidisciplinary approach has utilized advanced surgical techniques 4-6 complemented when appropriate with radiation and targeted therapies to achieve locoregional control in the settings of airway invasion and threat of organ preservation .
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Thyroid Vs Parathyroid: Whats The Difference
The names sound the same, but the thyroid and parathyroid glands are actually completely separate organs, with completely different functions in the body.
The thyroid gland plays a large role in regulating your metabolism. It affects things like body temperature, appetite and energy levels.
The parathyroid glands are actually a set of four glands, and their job is to control the amount of calcium in your blood. Having the proper calcium levels is important for maintaining proper bone density and nerve conduction.
So what do they have in common?
Well, since they both secrete hormones into the bloodstream, theyre both considered part of the bodys endocrine system, a broad term used to cover all of the bodys glands, including others like the adrenal glands and the pituitary gland too. Problems with glands usually manifest in one of two ways: they make too much of their hormones or too little. Like other parts of the body, glands are also vulnerable to cancer.
Theyre also both located within the neck. Typically, the parathyroid glands can be found just behind the thyroid, with both sitting in front of the wind pipe . Procedures to treat either one require a thorough understanding of the delicate anatomy of this area, which is why surgeons need special training to take care of thyroid and parathyroid disease.
New Therapies For Advanced Thyroid Cancer
- Surgical Oncology Program, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
Thyroid cancer is the most common endocrine cancer. The discovery of new biomarkers for thyroid cancer has significantly improved the understanding of the molecular pathogenesis of thyroid cancer, thus allowing more personalized treatments for patients with thyroid cancer. Most of the recently discovered targeted therapies inhibit the known oncogenic mechanisms in thyroid cancer initiation and progression such as MAPK pathway, PI3K/Akt-mTOR pathways, or VEGF. Despite the significant advances in molecular testing and the discoveries of new and promising therapeutics, effective treatments for advanced and metastatic, iodine-refractory thyroid cancer are still lacking. Here, we aim to summarize the current understanding of the genetic alterations and the dysregulated pathways in thyroid cancer and to discuss the most recent targeted therapies and immunotherapy for advanced thyroid cancer with a promising anti-tumor activity and clinical benefit.
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Targeted Therapies Attack Genetic Markers In Some Thyroid Cancers
Targeted therapies work by targeting genetic markers. Some of these new drugs target specific proteins expressed by mutated genes, such as the BRAF gene. Others disrupt new blood vessel growth to the tumor, which cuts off the cancers ability to grow. Targeted therapies are useful for cancers with specific DNA mutations. They may also be useful for cancers that stop responding to radioactive iodine.
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Drug Toxicities And Side Effects
Despite the different receptors targeted, the vast majority of TKI-related adverse events are common to different drugs. The most frequent AEs are diarrhea, anorexia, weight loss, fatigue, hypertension, hypothyroidism, hand-and-foot syndrome, and skin rash. The most frequent drug-related AEs for the different drugs investigated in the largest clinical trials are summarized in Table 5. The majority of these AEs are generally mild or moderate , and only in less than 510% of cases are they severe or life threatening , based on the common terminology criteria for adverse events . Death related to AEs is, fortunately, a very rare event.
| Sosa et al. |
MTC, medullary thyroid cancer DTC, differentiated thyroid cancer ATC, anaplastic thyroid cancer NE, not estimated.
The majority of AEs are easily prevented or managed with drug treatment, but in a nonnegligible percentage of cases, dose reduction , interruption , or withdrawal was needed in clinical trials .
International Study Shows Liquid Biopsies May Improve Lung Cancer Survival
An international study led by MSK investigators found that liquid biopsies may improve survival in people with lung cancer. Liquid biopsies are blood tests seeking to detect small amounts of cancer DNA floating in the blood, which can reveal the targeted drugs that are most likely to be effective for each patient. The study followed more than 1,000 people who were being treated for non-small cell lung cancer and had liquid biopsies. Of those who could be matched with targeted therapies based on molecular analysis, there was a 37% reduction in mortality. This research was published in Nature Medicine on November 10, 2022, and was led by Dr. Li and medical oncology fellow Justin Jee, MD, PhD.
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Anaplastic Thyroid Cancer Treatment
Anaplastic thyroid cancer is rare. But it is the most aggressive type of thyroid cancer and one of the most aggressive cancer types overall. Historically, few people with this disease are still alive one year after diagnosis. The disease had proved resistant to all tested therapies.
However in 2018, FDA approved the combination of two targeted drugs, dabrafenib mesylate and trametinib , for anaplastic thyroid cancers that have a certain mutation in the BRAF gene. About a quarter of anaplastic thyroid cancers carry this mutation.
Scientists at NCI and elsewhere are now looking for other mutations in anaplastic thyroid cancer that could be targeted with existing drugs. Through the collaboration between NCIs Surgical Oncology Program and the National Center for Advancing Translational Sciences , researchers are screening drugs approved for other conditions for the potential use of treating anaplastic thyroid cancer. Any promising drugs will eventually be tested at the NIH Clinical Center.
Treatment Planning And Monitoring
Treatment planning is an important step in thyroid cancer management. At HCG, we do preoperative imaging before surgery in order to locate the tumour precisely and plan the treatment as required.
Treatment monitoring, or response monitoring, is an important step of thyroid cancer treatment. During and after the treatment, certain tests are carried out to check if the patient is responding well to the treatment. Previously, advanced scans like MRI or CT scans were done to monitor the treatment response, and this became an unnecessary financial burden for patients. However, lately, we have identified a tumour marker called thyroglobulin. A simple blood test can help determine the levels of thyroglobulin, which can help specialists understand if the treatment is working well or needs to be altered.
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Related: In A Wily Protein That Helps Cancer Spread Researchers See A Chance To Make Immunotherapy More Effective
This paper wont change the recommendation, but doctors and scientists accept randomized trials. So, I think it will change hearts and minds on this topic, he said. That should help doctors and patients feel more comfortable foregoing radiation after thyroid surgery, Leboulleux said. Ultimately, she thinks that will be good for patients.
Radiation is just one more worry for a patient. Once you know that you dont need it, I dont think you should receive it, Leboulleux said.
Radioactive iodine still helps for high-risk thyroid cancer, where the malignancy has already spread throughout the body. Whether follow-up radiation is beneficial for more intermediate-risk thyroid cancers is still an open question, Leboulleux added. That is something she hopes to investigate next.
Fda Approves New Immunotherapy Combination To Treat Advanced Liver Cancer
On October 24, 2022, the FDA approved a combination of the immunotherapy drugs durvalumab and tremelimumab for people with unresectable hepatocellular cancer, the most common type of liver cancer. The approval was based on results of the clinical trial HIMALAYA involving 1,117 patients, led by MSK gastrointestinal medical oncologist Ghassan Abou-Alfa, MD. The results from the study showed after three years, about 30.7% of the patients who received the new combination immunotherapy were still alive, compared with 20.2% of the people who received only the kinase inhibitor drug sorafenib . In the group given durvalumab alone, 24.7% were still alive. In other words, the combination immunotherapy lowered the risk of death by 22%.
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Clinical Trials Of Targeted Therapies In Advanced Progressive Thyroid Cancer: The Experiences Of The Last Decade
| Sosa et al. |
DTC, differentiated thyroid cancer MTC, medullary thyroid cancer ATC, anaplastic thyroid cancer PR, partial response SD, stable disease PFS, progression-free survival OS, overall survival NE, not estimated.
Soon after the AMG706 study, an international, multicentric, phase 2 study examining the effect of axitinib on MTC and DTC was started . Fifty-two cases of locally advanced, unresectable, or metastatic MTC or RAI-R DTC with disease progression demonstrated in the previous 12 months were treated with 5 mg axitinib, orally administered twice daily. At the end of the study, 35% had a PR and 35% had an SD for 16 weeks or longer. The median PFS was 16.1 months, and the median overall survival was 27.2 months . In this study, as in the previous studies, the single-arm design makes the interpretation of the results rather difficult and, although the data appeared encouraging, no further studies have been planned for this drug.
Another promising drug for the treatment of patients with advanced thyroid cancer is pazopanib. This drug, which targets VEGFR, PDGF, c-KIT, and other kinases, was investigated in 39 patients with RAI-R and rapidly progressing metastatic DTC in a phase 2 study . Among the 37 patients who were able to be evaluated for a response, a PR was observed in 18 patients , with a calculated response duration longer than 1 year in 66% .
| Active, not recruiting | NCT01496313 |
New Surgical Techniques Help Reduce Scarring
Surgery to remove part or all of the thyroid gland is a common treatment for thyroid cancer. Its also one of the most effective treatments.
Until recently, surgery for thyroid cancer resulted in a scar on the neck. This is cosmetically bothersome for some people. Surgeons have developed new techniques that reduce or eliminate scarring on the neck and shorten recovery times. This includes endoscopic surgery that leaves smaller scars. There is also a new robotic-assisted surgery that reaches the thyroid gland through an incision in the armpit. This new surgery may not be available at all cancer centers yet. And its only right for some people. Talk with your doctor about your options.
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Combination Thyroid Hormone Therapies Treat Hypothyroidism As Well As Levothyroxine
Treatment should be individualized for common thyroid condition, researchers say
About Endocrine Society
Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the worlds oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.
The Society has more than 18,000 members, including scientists, physicians, educators, nurses, and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.
Advances In Thyroid Cancer Research
Micrograph of medullary thyroid carcinoma.
NCI-funded researchers are working to advance our understanding of how to treat thyroid cancer. The four main types of thyroid cancer are papillary, follicular, medullary, and anaplastic thyroid cancer.
Most thyroid cancers are found at an early stage and can be treated successfully. Scientists are now working to understand which people with thyroid cancer can safely choose less treatment for their disease, to minimize side effects. Research is also needed to find new treatments for rarer, aggressive types of thyroid cancer.
This page highlights some of the latest research in thyroid cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.
On This Page
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Innovative Drug Targets Her2 A Common Driver In Breast Cancer And Lung Cancer
- On August 5, 2022, the FDA approved the first targeted therapy for patients with HER2-low breast cancer that has spread to other parts of the body and is unable to be surgically removed. The drug, trastuzumab deruxtecan , was approved based on an international clinical trial led by MSK breast medical oncologist Shanu Modi, MD. Dr. Modis transformational study showed that T-DXd is able to block HER2 even when levels of the protein are low the case for about 55% of people with breast cancer. Dr. Modi presented the findings at the ASCO meeting on June 5, 2022, and the results were published in NEJM on the same day.