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Some benefit derived from immunotherapy for kidney cancer despite treatment discontinuation

Roshini Claire Anthony
01 Mar 2017

Patients with metastatic renal cell carcinoma (RCC) who discontinue immunotherapy due to adverse events can still derive clinical benefit, according to a small study presented at the American Society of Clinical Oncology (ASCO) 2017 Genitourinary Cancers Symposium (GU 2017) in Orlando, Florida, US.

“Responders to PD-1/PD-L1 targeted therapy can have persistent clinical benefit despite treatment discontinuation for immune-related adverse events,” said study lead author Dr Rana McKay, an Assistant Professor of Medicine at the University of California San Diego School of Medicine, California, US.

Forty-two percent of patients were considered durable responders, remaining off therapy for more than 6 months, while 16 percent were immediate progressors (<4 months off treatment). [ASCO GU 2017, abstract 467]

Among durable responders, median time on treatment prior to discontinuation was 11 months and median time off treatment was 20 months, while among immediate progressors, median time on and off treatment was 4 and 2 months, respectively. At time of analysis, 75 percent of durable responders were free from progression.

Participants in this retrospective analysis were individuals with metastatic RCC (n=19, median age 68 years, 74 percent male) treated with PD-1/PD-L1 targeted therapy who discontinued treatment due to immune-related adverse events. The patients were categorized based on their time off treatment after discontinuation – durable responders, immediate progressors, and others (4–6 months off treatment).

A majority of patients (58 percent) had received PD-1 monotherapy and median time on immunotherapy was 5.5 months. Fifty-eight percent of patients had received prior systemic therapy and 95 percent had clear cell histology.

“The current standard is to administer these treatments on a continuous basis until progression or toxicity,” said McKay. “PD-1/PD-L1 inhibitors are associated with a spectrum of side effects termed immune-related adverse events, which are thought to be due to immune system activation.”

Among the adverse events experienced by the subjects were arthritis, uveitis, myositis, blepharitis, hepatitis, pericarditis, pneumonitis, and nephritis. Eighty-four percent and 11 percent of patients required steroids and additional immunosuppressive agents, respectively, to treat their immune-related adverse events.

“One of the unintended consequences [of PD-1/PD-L1 inhibitors] is that besides eliciting an immune response against cancer, they may also potentially elicit an autoimmune response against one or multiple organs in the body,” said Dr Sumanta Pal who represented ASCO as moderator of the GU 2017 presscast.

“As [McKay] has nicely summarized, if the patient has immune-related side effects, the impact can be serious, but there is also the possibility that they could have a protracted benefit from the drug in terms of their cancer remaining dormant or shrinking for a protracted period of time. This supports the premise that those individuals who do experience immune-related side effects could have a tangible benefit from the drug, nonetheless,” said Pal.

Due to the small size of the study, larger, prospective studies are needed to “investigate approaches to customize immunotherapy based on response”, said McKay, stating that this will be carried out in the phase II OMNIVORE study.

 

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Most Read Articles
Audrey Abella, 09 Jun 2017
Maintenance therapy with olaparib significantly improved progression-free survival (PFS) and patient-centred benefits in patients with germline BRCA-mutated, platinum-sensitive relapsed serous ovarian cancer (gBRCAm PSR SOC) compared with placebo, according to the SOLO* 2 trial presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 held in Chicago, Illinois, US.
Elvira Manzano, 14 Jun 2017
The oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) in women with BRCA-positive, HER2-negative breast cancer compared with standard chemotherapy in the phase III OlympiAD* trial, ushering in a new era of hope in BRCA-mutated breast cancer.
Pearl Toh, 01 Aug 2016
Understanding biomarkers predictive of treatment outcomes or response can help inform treatment decisions and personalize care for advanced prostate cancer patients, suggested an expert at the recent Urological Association of Asia Annual Congress (UAA 2016) held in Singapore.
Audrey Abella, 13 Jun 2017
A psychological intervention, Conquer Fear, may help alleviate fear of cancer recurrence (FCR) in cancer survivors, according to a study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2017 held in Chicago, Illinois, US.