Key Advances in Oncology, 2018

Oncology (Williston Park). 33(1):6-8.

According to the American Cancer Society, there are more than 3.5 million breast cancer survivors in the United States. (image courtesy of Axel Kock/Adobe Stock)

T-cell lymphocyte with receptors for cancer cell immunotherapy research (image courtesy of catalin/Adobe Stock)

PC-3 human prostate cancer cells (image courtesy of Heitipaves/Adobe Stock)

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.[1] This represents an increase from 2017, in which the FDA approved 12 new oncology/hematology agents.[2] 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.[1]

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.

Breast Cancer

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.[3] 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.

Hematologic Cancer

“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.[4]

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.[5] Looking forward, the researchers hope to reduce continuous therapy of ibrutinib in light of its high cost and associated toxicities.

Immunotherapy

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.[6]

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.

Integrative Oncology

Santosh Rao, MD, the medical director of integrative medicine at Banner MD Anderson Cancer Center in Gilbert, Arizona, told ONCOLOGY he is excited about the advances made in integrative oncology. He and his colleagues foresee the inclusion of integrative medicine approaches in cancer management guidelines in the near future.

“Every year, there’s an increase in interest in integrative medicine. In 1996, integrative medicine was not well accepted,” he said. “We have come a long way in the last 20 years. More and more, positions are looking [to be filled by] clinicians and researchers who practice integrative oncology, and there will be more and more need as evidence grows. It’s definitely becoming more popular.”

Among many notable integrative oncology studies in 2018, Rao noted one that evaluated the effects of yoga on cognitive function in breast and ovarian cancer survivors as a standout. Lapen et al found that restorative yoga was better for the learning and processing of new information, whereas vigorous yoga was better at enhancing functions with regard to past memories.[10]

Rao also highlighted a study by Chen et al that examined the effects of Quxie capsules, a type of traditional Chinese medicine used in antiquity to treat various tumor types, on colorectal cancer. The researchers found that, in mouse models, Quxie capsules suppressed the growth of colorectal cancer, in part mediated by alterations in the gut microbiome. Moreover, possibly secondary to changes in the gut microbiome, Quxie capsules also upregulated the expression of myosin 11, which might play a role in tumor inhibition.[11]

Donald Abrams, MD, an integrative oncologist and professor of medicine at the University of California San Francisco’s Osher Center for Integrative Medicine, noted research published in JAMAOncology in October of this year that made waves in the field-but in a much more negative light. Conducted by Johnson et al of Yale School of Medicine, researchers found that cancer patients who utilized complementary medicine were more likely to refuse conventional treatment, and therefore had a higher risk of death compared with those who did not use complementary medicine.[12] According to Abrams, the study was unbalanced in that it compared a significantly smaller cohort of patients utilizing complementary therapies (258) compared with control (1,901,557), and the results thus “suggested that it [complementary medicine] was detrimental.”

Lung Cancer

The combination of either pembrolizumab or atezolizumab with chemotherapy made waves in the treatment of lung cancer in 2018, according to Apar K. Ganti, MD, an associate professor in the Department of Internal Medicine, Division of Oncology/Hematology, at the University of Nebraska Medical Center in Omaha.

With respect to metastatic non-squamous non–small-cell lung cancer (NSCLC), a global randomized controlled trial conducted by Paz-Ares et al found that adding pembrolizumab to chemotherapy (pemetrexed and carboplatin) nearly doubled the objective response rate (ORR) in patients. They also concluded that this combination proffers a tolerable safety profile.[13]

In the Hoffman-La Roche phase III IMpower132 study, researchers showed that the combination of atezolizumab plus chemotherapy (cisplatin or carboplatin plus pemetrexed) reduced the chances of disease progression or death vs sole chemotherapy in first-line treatment of advanced NSCLC.[14]

Prostate Cancer

Tomasz M. Beer, MD, deputy director, Grover C. Bagby Endowed Chair for Prostate Cancer Research, and professor of medicine at OSHU Knight Cancer Institute in Portland, Oregon, told ONCOLOGY that the introduction of two new agents for the treatment of high-risk, non-metastatic, castration-resistant prostate cancer was particularly important. Apalutamide and enzalutamide were approved by the FDA based on the findings of the SPARTAN[15] and PROSPER[16] trials, respectively.

In the SPARTAN trial, apalutamide decreased the risk of developing metastasis and death by 72% vs placebo.[15] In the PROSPER trial, enzalutamide lowered the chances of metastasis or death by 71% vs placebo.[16] In both studies, men were treated with ongoing androgen deprivation therapy.[15,16] On a historical note, the FDA approval of apalutamide was a first for patients with non-metastatic, castration-resistant prostate cancer.

Radiation Oncology

“For me, the big story in radiation [in 2018] was the emerging use of radiotherapy-most often SBRT [stereotactic body radiation therapy] for the treatment of oligometastatic disease,” James Yu, MD, MHS, director of Yale Medicine’s Prostate & Genitourinary Cancer Radiotherapy Program, told ONCOLOGY. “Several major studies presented at [the] ASTRO [American Society for Radiation Oncology meeting] or ESMO [the European Society for Medical Oncology meeting] are starting to validate the idea that aggressive treatment of disease with radiation and other local therapy such as surgery-even when [the cancer is] metastatic-may potentially improve outcomes.”

Yu specifically cited a phase II randomized controlled study in which Gomez et al found that local consolidative therapy plus or minus maintenance therapy for patients with three or fewer metastases from NSCLC that did not progress following initial systemic therapy enhanced PFS vs maintenance therapy alone. These findings indicate that aggressive local therapy has the potential to become a standard treatment alternative for these patients.[17]

Financial Disclosure:The authors have no significant financial interest in or other relationship with the manufacturer of any product or provider of any service mentioned in this article.

References:

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.