ASCO GU 2017: Some Patients Experience Long-Term Tumor Control Even After Stopping Immunotherapy Early

ALEXANDRIA, Va. – ( Early findings from a new study appear to challenge the current standard practice for immune checkpoint inhibitor therapy – continuing treatment until cancer worsens. Among patients with advanced kidney cancer who stopped PD1/PD-L1 immunotherapy early due to side effects, 42% had a durable response, meaning they were able to remain off additional systemic therapy for 6 months or more. More broadly, this insight may help alleviate some patients’ concerns about the impact of discontinuing immunotherapy. The study will be presented at the upcoming 2017 Genitourinary Cancers Symposium in Orlando.

Although there have been prior anecdotal data, this is the first systematic study evaluating the outcomes of patients with metastatic renal cell carcinoma (RCC) who stop PD-1/PD-L1 immune checkpoint inhibitor therapy due to immune-related side effects, according to the authors.

“In medicine, we are constantly balancing the benefits and risks of any given treatment,” said lead study author Rana R. McKay, MD, an Assistant Professor of Medicine at University of California San Diego School of Medicine. “This is a small study, and while our findings need to be validated in a larger group of patients, it underscores that in some cases, immunotherapy can have lasting benefits even after treatment discontinuation.”

The Study:
The analysis included a Harvard-led international cohort of 19 patients with advanced kidney cancer (metastatic renal cell carcinoma) that responded to immune checkpoint inhibitor therapy. The majority (63%) received PD-1/PD-L1therapy as a standalone treatment; 37% received PD-1/PD-L1 inhibitors in combination with other systemic treatments.
The median time on immunotherapy was 5.5 months. All patients stopped immunotherapy early due to immune-related adverse effects, such as joint pain; eye problems; pituitary gland, muscle, heart, liver, pancreas, kidney, or lung inflammation; and diarrhea.

Key Findings and Next Steps:
While in four patients, cancer worsened immediately after the treatment was stopped, eight (42%) patients had a durable response and remained off any additional therapy for at least six months from the time of treatment discontinuation. While these findings are novel and compelling, the study population was small, so the researchers hope to include more patients in the analysis in the future. This may provide clues as to what clinical characteristics are associated with a durable response to immunotherapy.
Meanwhile, the researchers are developing a prospective clinical trial that will further explore the efficacy of immunotherapy treatment discontinuation in patients responding to treatment.

About Kidney Cancer
An estimated 64,000 people will be diagnosed with kidney cancer in 2017 in the United States, and more than 14,400 will die of the disease.1 The rates of kidney cancer have been steadily rising over the last decade. Renal cell carcinoma is the most common type of adult kidney cancer, making up about 85% of diagnoses.
This study was funded by the Dana-Farber/Harvard Cancer Center Kidney SPORE, and the Trust Family, Michael Brigham, and Loker Pin.
1Cancer Facts & Figures 2017, American Cancer Society, 2017.

2017 Genitourinary Cancers Symposium: Presentation Information
Poster Session C
Saturday, February 18, 2017: 7:00 AM – 7:55 AM EST
Saturday, February 18, 2017: 11:30 AM – 1:00 PM EST
Rosen, Gatlin Ballroom B, Level 1
Rana McKay, MD
Dana-Farber Cancer Institute
Boston, Massachusetts

Abstract 467: Outcomes of PD-1/PD-L1 responders who discontinue therapy for immune-related adverse events (irAEs): Results of a cohort of patients (pts) with metastatic renal cell carcinoma (mRCC).

Authors: Rana R. McKay, Dylan Martini, Raphael Brandao Moreira, Lana Hamieh, Craig Norton, Stephanie Anne Mullane, Meghara K. Walsh, Dror Michaelson, David F. McDermott, Eliezer VanAllen, Lauren Christine Harshman, Toni K. Choueiri; Dana-Farber Cancer Institute, Boston, MA; Brigham and Women's Hospital, Boston, MA; Broad Institute, Dana-Farber Cancer Institute, Boston, MA; Massachusetts General Hospital Cancer Center, Boston, MA; Beth Israel Deaconess Medical Center, Boston, MA; Stanford University School of Medicine, Stanford, CA; Dana-Farber/Harvard Cancer Center, Boston, MA

Background: Nivolumab, a monoclonal antibody against PD-1, has been shown to improve survival for pts with mRCC. The current standard of care is to administer treatment on a continuous basis until progression or toxicity. Outcomes of pts who experience a response to treatment and then discontinue therapy for irAEs have not been fully characterized. The purpose of this analysis was to evaluate outcomes of responders to PD-1/PD-L1 targeted therapy (TT) who discontinue treatment for irAEs.

Methods: We identified pts with mRCC having experienced a response to PD-1/PD-L1 TT, which was subsequently discontinued for an irAE. Clinical characteristics, response, and survival data were collected.

Results: We identified 9 mRCC pts who were treated with a PD-1/PD-L1 inhibitor, experienced a response to therapy, and subsequently discontinued treatment for an irAE. 8 had clear cell histology and 1 had translocation RCC. 7 pts were treatment naive. 2 pts had International mRCC Database Consortium favorable risk, 4 intermediate risk, and 3 poor risk disease. 44% (n = 4) of pts received PD-1/PD-L1 monotherapy and the overall median duration of therapy was 5 months (mos) (range 4-15). There was 1 complete response, 7 partial responses, and 1 stable disease (17% shrinkage). Treatment was discontinued for the following irAEs: arthritis, uveitis, arthropathy, hypophysitis, myositis, blepharitis, hepatitis, rash, pericarditis, and amylase and lipase elevations. After PD-1/PD-L1 treatment discontinuation, 4 (44%) pts remained progression free with a median time off therapy of 20 mos (range 10-44) and median time on therapy of 9 mos (range 4-15). 5 (56%) pts progressed within 6 mos (range 2-6) of treatment discontinuation and median time on therapy was 4 mos (range 3-10).

Conclusions: We demonstrate that some pts can have persistent clinical benefit after discontinuation of PD-1/PD-L1 TT for irAEs. Larger studies are warranted to evaluate the need for continuous drug dosing in all pts, identify pts in which continuous dosing is not required, and evaluate long-term outcomes in this population.

2017 GU Cancers Symposium News Planning Team Sumanta K. Pal, MD, American Society of Clinical Oncology (ASCO); Daniel A. Hamstra, MD, PhD, American Society for Radiation Oncology (ASTRO); and Marc Dall’Era, MD, Society of Surgical Oncology (SSO)

About the American Society for Radiation Oncology: The American Society for Radiation Oncology (ASTRO) is the premier radiation oncology society in the world, with more than 10,000 members who are physicians, nurses, biologist, physicists, radiation therapists, dosimetrists and other health care professionals that specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, the Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology, Biology, Physics, Practical Radiation Oncology, and Advances in Radiation Oncology, developed and maintains an extensive patient website; and created the Radiation Oncology Institute, a non-profit foundation to support research and education efforts around the world that enhance and confirm the critical role of radiation therapy in improving cancer treatment. Learn more about ASTRO.

About the American Society of Clinical Oncology:
Founded in 1964, the American Society of Clinical Oncology, Inc. (ASCO®) is committed to making a world of difference in cancer care. As the world’s leading organization of its kind, ASCO represents more than 40,000 oncology professionals who care for people living with cancer. Through research, education, and promotion of the highest-quality patient care, ASCO works to conquer cancer and create a world where cancer is prevented or cured, and every survivor is healthy. ASCO is supported by its affiliate organization, the Conquer Cancer Foundation. Learn more at, explore patient education resources at www.Cancer.Net, and follow us on Facebook, Twitter, LinkedIn, and YouTube.

About the Society of Urologic Oncology: The Society of Urologic Oncology (SUO) was created in 1984 to enable qualified members primarily interested in the care of patients with malignant genitourinary diseases to meet for the purpose of discussion, development, and implementation of ideas to improve care. The Society and its bylaws conform to the guidelines and bylaws of the American Urological Association (AUA).

The purpose of the SUO is to develop educational and research initiatives and to study issues in urologic oncology and provide physician statements that represent a state of the art assessment of these issues to other organizations.

The Society also provides a forum for identifying the urologic oncologist as a physician with specific expertise in the study and treatment of genitourinary malignancies. In recognition of the multidisciplinary efforts involved in the study and treatment of genitourinary malignancies, the Society seeks to incorporate multiple disciplines in achieving these goals. The Society supports the activities of multiple disciplines in the common objectives of seeking an increased understanding and successful treatment of genitourinary malignancies.

The SUO seeks to improve the care of patients with malignant urologic disease and to provide a forum for the discussion of problems relating to malignant urologic disease. Our objectives include: 1) Stimulating research in and the teaching of urologic oncology, 2) Disseminating the principles of urologic oncology to the medical profession at large, 3) Bringing urologists into a Society whose work is entirely, or principally with malignant disease, 4) Being identified as the most qualified organization on matters relating to urologic oncology, and 5) Standardize fellowship training in urologic oncology.