A Notable Year
When considering the key advances in oncology this past year, the candidates are numerous. Oncology, by necessity, evolves at an ever more rapid pace. In 2018, the US Food and Drug Administration (FDA) approved a record 59 new drugs across all medical specialties; of these, 17 (29%) approvals were relevant to oncology/hematology specifically. This represents an increase from 2017, in which the FDA approved 12 new oncology/hematology agents. Of note, 8 of the 17 oncology/hematology approvals in 2018 are indicated for the treatment of various blood cancers, illustrating that particularly significant progress was made in this cancer subtype.
In addition to noting newly approved oncology/hematology agents, it is important that oncology clinicians also familiarize themselves with the most impactful research in order to continue to improve safety, survival, and quality of life in cancer patients. Here, members of ONCOLOGY’s Editorial Board, as well as the wider oncology community, provide feedback on the most significant advances of 2018.
When it comes to breast cancer, one study in 2018 stands out, according to I. Craig Henderson, MD, an adjunct professor in the Department of Medicine (Hematology/Oncology) at the University of California San Francisco’s Helen Diller Family Comprehensive Cancer Center and a member of ONCOLOGY’s Editorial Board. The research, published in the New England Journal of Medicine, found that the risk of invasive recurrence of human epidermal growth factor receptor 2–positive, early-stage breast cancer was 50% lower in patients treated with ado-trastuzumab emtansine compared with those who received trastuzumab alone. This finding supports the use of ado-trastuzumab emtansine as a new standard of care in these patients, said Henderson.
“I believe these results will be practice-changing,” wrote study author Charles E. Geyer, Jr, MD, a professor of medicine at Virginia Commonwealth University School of Medicine and the associate director for clinical research at Massey Cancer Center in Richmond, Virginia, in a statement. “The results should form the foundation of a new standard of care in patients with residual invasive breast cancer following neoadjuvant therapy.”
For more top breast cancer news from SABCS 2018, see our Oncology Conference Highlights, Q4 on pages 8–10 of this issue.
“Probably the most significant [studies of 2018] were the two CLL [chronic lymphocytic leukemia] studies that establish ibrutinib as the standard of care for front-line treatment of CLL in the younger and older populations, respectively,” according to John Sweetenham, MD, executive medical director and senior director of clinical affairs at Huntsman Cancer Institute in Salt Lake City, Utah, and a member of the ONCOLOGY Editorial Board. The results of both studies were presented at the 2018 ASH Annual Meeting and Exposition, held in December in San Diego.
One of these studies—a phase III trial conducted by Shanafelt et al (LBA-4)—found that a combination of ibrutinib and rituximab enhanced progression-free survival (PFS) and overall survival (OS) compared with fludarabine, cyclophosphamide, and rituximab (FCR) in patients aged 70 years or younger with treatment-naive CLL. According to the researchers, these findings establish ibrutinib-based therapy as the most effective first-line therapy for patients with CLL.
The other study—a phase III trial conducted by Woyach et al—concluded that ibrutinib produces superior PFS compared with standard chemoimmunotherapy in patients aged 65 years or older with treatment-naive CLL. However, the addition of rituximab to ibrutinib failed to lengthen PFS. These results support ibrutinib as a standard-of-care treatment in elderly patients. Looking forward, the researchers hope to reduce continuous therapy of ibrutinib in light of its high cost and associated toxicities.
One particularly noteworthy highlight in the field of immunotherapy occurred in October of this year, when the Nobel Prize in Physiology or Medicine was awarded to James P. Allison of the United States and Tasuku Honjo of Japan for their work on cancer immunotherapy. Their findings on checkpoint inhibitors “brought immunotherapy out from decades of skepticism,” Dr. Jedd Wolchok, a cancer specialist at Memorial Sloan Kettering Cancer Center in New York, wrote in a New York Times article announcing the award.
Mario M. Leitao, Jr, MD, a gynecologic oncologist and director of the Minimal Access and Robotic Surgery Program at Memorial Sloan Kettering Cancer Center, pointed to the clinical impact of several Poly(ADP-ribose) polymerase (PARP) inhibitors: niraparib, olaparib, and rucaparib. These agents, which received FDA approval in short order starting in 2014, fundamentally change the management of BRCA-associated ovarian cancer.[7-9] Of interest, niraparib is also effective at treating ovarian tumors without alterations in BRCA 1/2. Nevertheless, it remains to be elucidated how to best integrate PARP inhibitors into combination treatment strategies.
1. US Food & Drug Administration. Novel drug approvals for 2018. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm592464.htm. Updated January 8, 2019. Accessed January 9, 2019.
2. US Food & Drug Administration. Novel drug approvals for 2017. https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm537040.htm. Updated February 2, 2019. Accessed January 9, 2019.
3. Geyer Jr CE, Huang CS, Mano MS, et al. A study of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor in the breast or axillary lymph nodes following preoperative therapy (KATHERINE). Presented at the San Antonio Breast Cancer Symposium; December 5, 2018; San Antonio, Texas.
4. Shanafelt TD, Wang V, Kay NE, et al. A Randomized Phase III Study of Ibrutinib (PCI-32765)-Based Therapy Vs. Standard Fludarabine, Cyclophosphamide, and Rituximab (FCR) Chemoimmunotherapy in Untreated Younger Patients with Chronic Lymphocytic Leukemia (CLL): A Trial of the ECOG-ACRIN Cancer Research Group (E1912). Presented at the 2018 American Society of Hematology Annual Meeting & Exposition; December 4, 2018; San Diego, California. Abstract LBA-4.
5. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib Alone or in Combination with Rituximab Produces Superior Progression Free Survival (PFS) Compared with Bendamustine Plus Rituximab in Untreated Older Patients with Chronic Lymphocytic Leukemia (CLL): Results of Alliance North American Intergroup Study A041202. Presented at the 2018 American Society of Hematology Annual Meeting & Exposition; December 4, 2018; San Diego, California. Abstract 6.
6. Grady D. 2018 Nobel Prize in Medicine Awarded to 2 Cancer Immunotherapy Researchers. New York Times. https://www.nytimes.com/2018/10/01/health/nobel-prize-medicine.html. Published October 1, 2018. Accessed December 19, 2018.
7. US Food & Drug Administration. Approvals: Niraparib (ZEJULA). https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm548487.htm. Published March 27, 2017. Accessed December 19, 2018.
8. US Food & Drug Administration. FDA approves olaparib for germline BRCA-mutated metastatic breast cancer. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm592357.htm. Published January 12, 2018. Accessed December 19, 2018.
9. US Food & Drug Administration. FDA approves rucaparib for maintenance treatment of recurrent ovarian, fallopian tube, or primary peritoneal cancer. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm603997.htm. Published April 6, 2018. Accessed December 19, 2018.
10. Lapen K, Benusis L, Pearson S, et al. A feasibility study of restorative yoga versus vigorous yoga intervention for sedentary breast and ovarian cancer survivors. Int J Yoga Therap. 2018;28:79-85.
11. Chen D, Yang Y, Yang P. Quxie Capsule Inhibits the Colon Tumor Growth Partially Mediated by Modulating the Gut Microbiome and Myosin11; poster #2. Presented at the Gulf Coast Consortia 2nd Annual Antimicrobial Resistance and Gut Health Symposium; June 15, 2018; Houston, Texas.
12. Johnson SB, Park HS, Gross CP, et al. Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers. JAMA Oncol. 2018;4:1375-81.
13. Paz-Ares LG, Luft A, Tafreshi A, et al. Phase 3 study of carboplatin-paclitaxel/nab-paclitaxel (Chemo) with or without pembrolizumab (Pembro) for patients (Pts) with metastatic squamous (Sq) non-small cell lung cancer (NSCLC). Presented at the American Society of Clinical Oncology Annual Meeting; June 3, 2018, Chicago, Illinois. Abstract 105.
14. Papadimitrakopoulou VA, Cobo M, Bordoni R, et al. IMpower132: PFS and Safety Results with 1L Atezolizumab + Carboplatin/Cisplatin + Pemetrexed in Stage IV Non-Squamous NSCLC. Presented at the International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer; September 23-26, 2018; Toronto, Canada.
15. Small EJ, Saad F, Chowdhury S, et al: SPARTAN, a phase 3 double-blind, randomized study of apalutamide versus placebo in patients with nonmetastatic castration-resistant prostate cancer. Abstract 161. Presented at the 2018 Genitourinary Cancers Symposium; February 8, 2018; San Francisco, California.
16. Hussain M, Fizazi K, Saad F, et al: PROSPER: A phase 3 randomized, double-blind, placebo-controlled study of enzalutamide in men with nonmetastatic castration-resistant prostate cancer. Abstract 3. Presented at the 2018 Genitourinary Cancers Symposium; February 8, 2018; San Francisco, California.
17. Gomez DR, Blumenschein GR Jr, Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016;17:1672-82.