A Conquer Cancer Foundation Award Helps to Launch a Pioneering Study in Liposarcoma

A Conversation With Mark A. Dickson, MD


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Mark A. Dickson, MD

Mark A. Dickson, MD

Mark A. Dickson, MD, has been fascinated by science and medicine since he was in high school. After graduating magna cum laude from Harvard University in 1999, Dr. Dickson pursued a medical degree from the College of Physicians and Surgeons at Columbia University in New York. Once he decided on a career in medicine, he knew he would specialize in oncology.

“It became clear to me that cancer was probably the biggest public-health problem we were going to face over the next century,” said Dr. Dickson. “Studying cancer appealed to me on a couple of levels: first, as a compelling intellectual problem to try and solve and second, as a way to make a significant contribution to better health outcomes for society.”

After completing his residency in internal medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and then serving as Assistant Chief Resident in Medicine there, Dr. Dickson moved to Memorial Sloan Kettering Cancer Center (MSK) in 2006 for fellowship training in hematology and medical oncology and was named Chief Fellow in Hematology/Oncology the following year. He is now Assistant Attending Physician at MSK and Assistant Professor of Medicine at Weill Cornell Medical College.

While working with his mentors Gary Schwartz, MD, then Chief of the Melanoma and Sarcoma Service at MSK, and Robert Maki, MD, PhD, a renowned researcher in soft-tissue sarcomas, Dr. Dickson decided to dedicate his research efforts to advance the treatment of this diverse and relatively rare group of malignant tumors that develop in the soft tissue and bone. These malignant tumors are diagnosed in more than 12,000 people each year in the United States and kill nearly 5,000 individuals annually.1

Early Achievements

A turning point in Dr. Dickson’s research career came in 2011, when he received the Conquer Cancer Foundation of ASCO Career Development Award, which he used to fund a small phase II clinical trial of the CDK4 inhibitor PD-0332991 (palbociclib [Ibrance]) in patients with advanced well-differentiated and dedifferentiated liposarcomas.2 The study found that the drug, which was approved by the U.S. Food and Drug Administration (FDA) in 2015 in the treatment of hormone receptor–positive HER2-negative advanced breast cancer, was associated with a favorable progression-free survival in patients with CDK4-amplified and retinoblastoma protein–expressing well-differentiated liposarcomas/dedifferentiated liposarcomas who had progressive disease despite systemic therapy. (The result from a larger clinical trial3 of palbociclib in patients with advanced well-differentiated or dedifferentiated lipsosarcomas has also found the drug to have activity in the disease.)

“We looked at two measures,” said Dr. Dickson. “One was the response rate in shrinking the tumors, but that was extremely rare. What we saw in most patients was stable disease, and in some cases, their disease was stable for many months. Some people on the trial had been in the study for several years and continued to maintain stable tumors, so that was a beneficial finding. The primary endpoint of the study was the number of patients who had stable tumors after 3 months of therapy, and about 66% of the patients achieved that endpoint, which was considered relatively favorable, given the history of liposarcoma in prior trials.”

Without the ASCO Career Development Award, said Dr. Dickson, his research would not have been possible. “Liposarcoma is an orphan disease, so there is not a lot of support from pharmaceutical companies for research in this cancer, and getting funding from the National Cancer Institute is extremely difficult for young investigators,” he explained. “Also, the Career Development Award is one of the most prestigious awards an investigator can receive and it helped to establish my credentials at MSK and allowed me protected time to do my research.” Dr. Dickson is also a past recipient of the Conquer Cancer Foundation’s Young Investigator Award.

The Complexity of Sarcomas

Dr. Dickson is now planning a new trial for liposarcoma patients with another CDK4 inhibitor called abemaciclib (previously known as LY2835219), which is a very different molecule from palbociclib and has greater selectivity for the CDK4 protein. (A new study published in Cancer Discovery has found that single-agent abemaciclib achieved durable clinical activity in several cancer types, including breast, lung, glioblastoma, and melanoma.4)

In oncology, you have to be very patient and have reasonable expectations, but it is also important to keep your nose to the grindstone and stay optimistic, because great breakthroughs can happen very quickly. I’m hoping that prime time for sarcoma is coming in the next few years.
— Mark A. Dickson, MD

To help predict which patients with liposarcoma might reap the biggest benefit from abemaciclib, Dr. Dickson plans to perform next-generation sequencing on patients’ tumors at the start of the trial and again 1 month after starting therapy to determine whether the drug is hitting its molecular target.

“What we are learning through our research is that liposarcomas are complex heterogeneous cancers with many subtypes. In addition to CDK4 amplifications, they often have MDM2 amplifications, which makes treatment challenging.”

Dr. Dickson is also eagerly awaiting the results of two clinical studies investigating the programmed cell death protein 1 (PD-1) inhibitors nivolumab (Opdivo) and pembrolizumab (Keytruda) in the treatment of liposarcoma. “It is going to be incredibly interesting to see which subtypes of sarcoma respond to immunotherapies like nivolumab and pembrolizumab and which do not. I’m hopeful that immunotherapy will prove to be another helpful strategy for liposarcoma,” declared Dr. Dickson. “2016 is shaping up to be an incredibly exciting year for the discovery of new therapies for sarcoma.”

Awaiting the Next Breakthrough

In addition to his research, Dr. ­Dickson has a busy clinical practice and sees up to 25 patients a day, many with liposarcomas. Soon, he hopes to be able to offer his patients more effective therapy than what is currently available.

“In oncology, you have to be very patient and have reasonable expectations, but it is also important to keep your nose to the grindstone and stay optimistic, because great breakthroughs can happen very quickly. For 20 years in melanoma, for example, there were hardly any new drugs for that cancer. In the past 5 years, there have been seven FDA-approved drugs. I’m hoping that prime time for sarcoma is coming in the next few years,” concluded Dr. Dickson. ■

Disclosure: Dr. Dickson has consulted for Pfizer on one occasion.

References

1. American Cancer Society: What are the key statistics about soft tissue sarcomas? Available at www.cancer.org/cancer/sarcoma-adultsofttissuecancer/detailedguide/sarcoma-adult-soft-tissue-cancer-key-statistics. Accessed June 9, 2016.

2. Dickson MA, Tap WD, Keohan ML, et al: Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma. J Clin Oncol 31:2024-2028, 2013.

3. Dickson MA, Schwartz GK, Keohan ML, et al: Progression-free survival among patients with well-differentiated or dedifferentiated liposarcoma treated with CDK4 inhibitor palbociclib: A phase 2 clinical trial. JAMA Oncol. April 28, 2016 (early release online).

4. Patnaik A, Rosen LS, Tolaney SM, et al: Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors. Cancer Discov. May 23, 2016 (early release online).



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