2021 in Review: 10 Important Clinical Advances in Cancer at MSK

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In 2021, MSK physician-scientists made important advances in patient care for cancers of the lung, breast, prostate, and more.

In 2021, Memorial Sloan Kettering Cancer Center doctors and scientists continued to make major discoveries that will improve the treatment of cancer. Philanthropic donations provided critical support for much of this research, allowing clinical researchers to pursue innovative ideas and take necessary risks to make breakthrough discoveries.

1. Excellent Outcomes for New Leukemia and Lymphoma Drug

The first-ever clinical trial of a new kind of drug for blood cancer showed promising results. The drug, called pirtobrutinib or LOXO-305, was tested in people with one of several kinds of leukemia and lymphoma, including chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma, as well as other types of non-Hodgkin lymphoma.

“This drug appears to be effective in patients who have stopped responding to all other standard treatments,” says MSK hematologic oncologist Anthony Mato, the lead author of a paper about the study, which was published March 4, 2021, in The Lancet. “In addition, the rate of mild or severe side effects was very low. It’s a great combination of being very active even in the sickest patients and being very well tolerated.”

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2. Immunotherapy Drug Lowers Risk of Bladder Cancer Returning after Surgery

People whose bladder cancer has spread into the muscle wall may soon have a new treatment option that will help keep the cancer from returning after surgery. A large, international clinical trial showed that the immunotherapy drug nivolumab (Opdivo®) is effective at reducing bladder cancer recurrence. About 25% of bladder cancers fall into this high-risk category, in which the disease is much more likely to spread and is harder to treat.

“It’s a major advance,” says MSK medical oncologist and Frederick R. Adler Senior Faculty Chair Dean Bajorin, who played a major role in the clinical trial and presented results at the annual Genitourinary Symposium of the American Society of Clinical Oncology in February 2021. “The absence of good treatment options has been frustrating for both patients and doctors — to know someone has high-risk disease and yet not be able to offer them a treatment to reduce recurrence. Now, for the first time, a new immunotherapy accomplishes exactly that.”

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3. First-Ever KRAS Inhibitor Approved for ’Undruggable’ Lung Cancer Target

On May 28, 2021, the US Food and Drug Administration announced the approval of sotorasib (LumakrasTM) for the treatment of certain advanced non-small cell lung cancers in patients who have already received at least one other treatment. The approval was based on clinical trials co-led by MSK medical oncologist Bob Li.

“This approval marks a major milestone in targeted therapies and changes the treatment paradigm for patients with KRAS-G12C-mutated non-small cell lung cancer,” Dr. Li explains. “Researchers and physicians at Memorial Sloan Kettering have had their sights set on this target for nearly 40 years, and with this first-of-its-kind approval, we have taken an important first step in cracking KRAS and providing a new treatment option for patients.”

Research continues at MSK to make this therapy work for even more people with lung cancer. On November 10, 2021, physician-scientist Piro Lito and Dr. Li reported why some patients develop resistance to sotorasib. The findings have implications for developing new drugs to counteract this resistance, as well as for identifying drugs that may work for patients who don’t ever respond to sotorasib.

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4. Better Ways to Detect and Treat Advanced Prostate Cancer

Prostate cancer treatment stands on the brink of a major advance with the development of a new therapy that zeros in on metastatic cancer cells to destroy them. The therapy, called 177Lu-PSMA-617, uses a molecule that selectively seeks out and attaches to a specific protein on the cancer cell surface. The technology then delivers radiation that damages DNA and destroys the cancer cell. This treatment can find and demolish cancer cells that are resistant to other therapies.

“Effective treatments are limited for metastatic prostate cancer that has progressed despite treatments that target the androgen receptor and chemotherapy, so this could be a game changer,” says MSK medical oncologist Michael Morris.

On May 27, 2021, the US Food and Drug Administration approved a new prostate cancer imaging test based on similar technology. On a PET scan, the test lights up the cancerous cells that would otherwise be hidden, enabling doctors to precisely target treatment.

“The benefits these advances will bring to men with this common disease cannot be overstated,” Dr. Morris says.

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Philanthropic support for this research was provided by the Magnier family.

A Promising New Therapy for Advanced Prostate Cancer
A new treatment that selectively seeks out prostate cancer cells shows great promise for treating advanced forms of the disease.
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5. A Breakthrough for People Facing Gastric and Esophageal Cancer

The US Food and Drug Administration (FDA) approved new treatment options for people with advanced esophageal cancer or stomach cancer (gastric cancer) thanks to clinical trials at MSK. The new treatments involve combining the immunotherapy drug pembrolizumab (Keytruda®) with standard treatments for patients with HER2-positive tumors of the esophagus or stomach. About 1 out of 5 people with esophageal or stomach cancer have HER2-positive tumors, and the gene can also play a role in many other cancers, including breast cancer.

The trials were led by Yelena Janjigian, a physician-scientist and Chief of the Gastrointestinal Oncology Service. The FDA gave accelerated approval to the therapy in May 2021, adding gastric and gastroesophageal cancers to the growing list of malignancies for which immunotherapy can help.

“Being able to tell people with stage 4 cancer that I now can’t see any signs of cancer is probably one of the most satisfying moments in my career,” she says.

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Philanthropic support for this research was provided by Cycle for Survival and Fred’s Team.

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6. MSK Collaborates with BioNTech to Test mRNA Vaccines Against Pancreatic Cancer

MSK researchers are investigating the potential of deploying messenger RNA (mRNA) vaccines against pancreatic cancer. A collaboration with BioNTech — which developed the Pfizer-BioNTech COVID-19 vaccine — has led to a clinical trial testing this new treatment. The trial is led by physician-scientist Vinod Balachandran, who discovered several years ago why some people with pancreatic cancer survive many years after diagnosis. In these patients, the immune system keeps the cancer from returning.

The new trial uses mRNA vaccines based on this concept. The vaccine is being tested in pancreatic cancer patients in combination with another type of immunotherapy. The phase 1 trial was completed in June 2021.

“This has been a great example of MSK’s forward-thinking vision in cancer care — to bring the most exciting medicines to cancer patients,” Dr. Balachandran says.

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Philanthropic support for this research was provided by the Lustgarten Foundation and Stand Up 2 Cancer.

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7. Study Identifies Biomarker That May Help Predict Benefits of Immunotherapy

Despite the excitement surrounding immune checkpoint inhibitors, a frustrating sticking point has been the inability to predict who will benefit from them and who will not. MSK researchers may have taken a step toward resolving this problem with a discovery that a specific pattern, or “signature,” of markers on immune cells in the blood is a likely biomarker of response to the drugs. Within this immune signature, a molecule called LAG-3 provides key information identifying patients with poorer outcomes. They reported the findings on August 25, 2021, in Science Translational Medicine.

“If I told you that you could have a simple blood draw and in a couple of days have information to make a decision about what therapy you get, I’d say it doesn’t get much better than that,” says Margaret Callahan, an investigator with the Parker Institute for Cancer Immunotherapy at MSK and the physician-researcher who led the study.

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Philanthropic support for this research was provided by the Parker Institute for Cancer Immunotherapy and The Society of Memorial Sloan Kettering.

Parker Institute for Cancer Immunotherapy
A unique collaboration of immunologists at MSK and five other academic medical centers that is devoted to pursuing research in cancer immunotherapy.
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8. A Targeted Drug Developed for Breast Cancer Is Helping People with Lung Cancer

Results from a phase 2 clinical trial showed that the breast cancer targeted therapy called trastuzumab deruxtecan (Enhertu®) could be effective against a type of lung cancer. The drug shrank tumors in more than half of people with advanced lung cancer driven by the HER2 protein.

“For a patient population in which standard treatments have failed, this is a significant advancement,” says MSK medical oncologist Bob Li, who led the trial and reported results at the 2021 annual meeting of the European Society for Medical Oncology in September. The study also was published in the New England Journal of Medicine.

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9. New Finding Could Predict Which People with Lung Cancer Will Benefit from Chemotherapy

People with stage 2 or 3 lung adenocarcinoma, the most common form of lung cancer, usually receive chemotherapy after surgery to try to kill any undetected tumor cells. However, only 5% to 15% of patients with lung cancer benefit from chemotherapy after surgery. This means that the vast majority endure months of chemotherapy treatment — and its side effects — without extending their survival.

Thoracic surgeon Prasad Adusumilli and his colleagues at MSK found a biomarker that could help identify patients who will respond to chemotherapy. They also found evidence suggesting that the immune system is involved in this response. By studying lung cancer tumors in the lab, they discovered that high levels of a protein called PD-L1 were associated with patients living longer after chemotherapy. They reported the findings October 8, 2021, in the Journal of Thoracic Oncology.

“This could be an important step toward finding better ways to combine chemotherapy and immunotherapy for patients with stage 2 and 3 lung cancer,” Dr. Adusumilli says.

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Philanthropic support for this research was provided by the Joanne & John Dallepezze Foundation, Batishwa Fellowship, the Comedy vs Cancer Award, the Derfner Foundation, the Esophageal Cancer Education Fund, the Geoffrey Beene Foundation, the Memorial Sloan Kettering Technology Development Fund, the Miner Fund for Mesothelioma Research, William H. Goodwin and Alice Goodwin, the Commonwealth Foundation for Cancer Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center.

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10. A Milestone for Precision Oncology: FDA Gives Green Light to MSK’s Genetic Database

In October 2021, the US Food and Drug Administration gave partial recognition to OncoKB, a genetic variant database developed at MSK to interpret the usefulness of tumor mutations for predicting drug responses. The recognition means that OncoKB is considered a scientifically valid tool for this purpose.

From the early years of targeted therapy, doctors and scientists at MSK understood that they needed a better way to keep track of which mutations were most clinically relevant for each kind of cancer. To do that, they developed a searchable database, which they named OncoKB. (The “KB” stands for “knowledge base.”)

“There are so many cancer-causing mutations that no one can memorize all of them,” says physician-scientist David Solit, Director of MSK’s Marie-Josée and Henry R. Kravis Center for Molecular Oncology, which maintains the database. “We created OncoKB as a tool to help doctors understand which mutations in a particular gene are important and may predict for sensitivity or resistance to a particular drug.” Dr. Solit is also Geoffrey Beene Chair at MSK.

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