Recent Cancer Advances from a Student Perspective

Charolette Walmsley

Prior to medical school, my first foray into patient care occurred at the Massachusetts General Hospital Cancer Center, working one-on-one with cancer patients receiving first-in-human clinical trial drugs. The patients came in hopes of extending their lives or even finding the silver bullet at the cost of a host of side effects — anything from mouth sores to deadly immune reactions. Despite the high stakes and abundant side effects, the Henri and Belinda Termeer Center for Targeted Therapies was a hopeful and exciting place. Everyone, patients and caretakers alike, knew the field of oncology was moving at light speed. Each year, groundbreaking treatments were shooting through the clinical trials pipeline, settling into clinical practice and saving lives. Observing this combination of bravery, hope, heartbreak and triumph inspired me to pursue my dream of becoming an oncologist. I would like to walk you through the recent advances in cancer treatments and hopefully instill you with some of my excitement for the field. The possibilities in oncology are truly endless.

Prior to the 2000s, first-line cancer therapy followed a similar formula: surgery, when possible, followed by chemotherapy. To the benefit of innumerable patients, this paradigm was upended following the arrival of immunotherapy and targeted therapy. Targeted therapy came on the scene slightly earlier than immunotherapy with the landmark approval of Herceptin as a treatment for early-stage breast cancer in 2006 (1). Herceptin, like other targeted therapies, is engineered to attack a specific protein on the surface of cancer cells providing a more targeted approach. In contrast, immunotherapy is a strategy centered around using the body’s natural defenses, the immune response, to target and kill cancer cells. Designated as the cancer advance of the year in 2016, the American Society of Clinical Oncology wrote: “clinical trials of promising approaches followed one after another (2).” Later that year, the U.S. Food and Drug Administration approved a wave of immunotherapies for the treatment of bladder cancer, Hodgkin lymphoma, and head, neck, and lung cancers.

However promising, a major shortcoming of immunotherapies — and a surprising turn of events for many oncologists — was the unpredictability of which patients would benefit from immunotherapy. A handful of patients would experience a major response, where others would see little to no benefit. Fortunately, the unprecedented success of immunotherapy continued in 2017 as new technologies were developed to detect which patients would benefit from immunotherapy based on the presence of genetic mutations (3).

In 2018, a new, groundbreaking type of immunotherapy known as chimeric antigen receptor T-cell therapy, or CAR-T, took the oncology world by storm. CAR-T is a technique that genetically reprograms patients’ immune cells to fight cancer. In this type of treatment, a patient’s T-cells are removed and genetically altered to find and kill cancer cells. Not only is it extremely efficacious in a number of patients, but CAR-T is also living therapy that continues to work over time (4).

There is no better demonstration of the power of CAR-T than its impact on pediatric acute lymphoblastic leukemia, or AL. For kids with ALL who do not respond to the first-line treatments, approximately 10%, survival is often measured in weeks. However, Kymriah, a type of CAR-T, sent 52 of 63 patients into remission in the ENSIGN clinical trial (National Clinical Trial number NCT02228096), prompting the FDA to approve Kymriah to treat pediatric ALL patients (5). This same treatment was also used on patients with recurrent non-Hodgkin lymphoma and multiple myeloma sending a large portion of those patients into lasting remission — a truly remarkable success (6). Despite the wondrous effects of CAR-T, a major drawback is the many serious and often unpredictable side effects of treatment which include inflammatory reactions and neurologic problems. Clearly no major breakthrough is without drawbacks, especially in the field of oncology.

Let’s continue. In 2019, the major advances occurred in the realm of targeted therapies, a type of treatment engineered to target a patient’s specific cancer genes or proteins. In the recent past, these therapies have been particularly efficacious for rare cancers, making up approximately 20% of all cancer cases. One notable example is anaplastic thyroid cancer. Known as one of the most insatiable and destructive cancers, anaplastic thyroid cancer had a median overall survival of 35% at four months, according to the Surveillance, Epidemiology and End Results database analysis (1986-2015) (7). A combination treatment of two targeted therapies, a BRAF inhibitor and an MEK inhibitor, led to durable responses in 69% of patients with recurrent anaplastic-thyroid cancer (8). That is a significant amount given the devastating prognosis of anaplastic thyroid cancer. Similar advances occurred in the treatment of soft-tissue sarcoma.

Back to our initial paradigm, we can’t leave out surgery. Given the array of new efficacious medical therapies, the role of surgery has adapted to better fit the needs of patients. Starting in 2019, clinical trials in advanced melanoma, kidney cancer and pancreatic cancer showed that treating patients with systemic therapies prior to surgery can improve outcomes and lead to more effective, less-invasive surgeries9. A win-win.

I hope, at the very least, I’ve expressed the exponential rise in cancer discoveries in the recent past. I also hope that my excitement for the field is evident in my words as I find enthusiasm is often contagious. Ultimately, I hope to live in a world where cancer is a chronic disease instead of a fatal one. It is truly a remarkable time to be embarking on a career in cancer medicine.

Charlotte Walmsley is a fourth-year medical student at the The University of Massachusetts Chan Medical School.

References:

1. Bartsch, Rupert et al. “Trastuzumab in the management of early and advanced stage breast cancer.” Biologics : targets & therapy vol. 1,1 (2007): 19-31.

2. Dizon, Don S et al. “Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 34,9 (2016): 987-1011. doi:10.1200/ JCO.2015.65.8427

3. Burstein, Harold J et al. “Clinical Cancer Advances 2017: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 35,12 (2017): 1341-1367. doi:10.1200/ JCO.2016.71.5292

4. Heymach, John et al. “Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 36,10 (2018): 1020-1044. doi:10.1200/ JCO.2017.77.0446

5. Mueller, Karen Thudium et al. “Tisagenlecleucel Immunogenicity in Relapsed/Refractory Acute Lymphoblastic Leukemia and Diffuse Large B-Cell Lymphoma.” Blood advances, bloodadvances.2020003844. 25 Aug. 2021, doi:10.1182/bloodadvances.2020003844

6. Pal, Sumanta K et al. “Clinical Cancer Advances 2019: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 37,10 (2019): 834-849. doi:10.1200/ JCO.18.02037

7. Lin B, Ma H, Ma M, et al. . The incidence and survival analysis for anaplastic thyroid carcinoma: a SEER database analysis. Am J Transl Res. 2019;11(9):5888-5896.

8. Subbiah, Vivek et al. “Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 36,1 (2018): 7-13. doi:10.1200/JCO.2017.73.6785

Markham, Merry Jennifer et al. “Clinical Cancer Advances 2020: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 38,10 (2020): 1081. doi:10.1200/ JCO.19.03141