Delayed Adverse Events
Christopher G. Wood, MD, professor and deputy chairman of the Department of Urology at The University of Texas MD Anderson Cancer Center in Houston, TX, said he believes deferred systemic therapy is an appropriate way to address the adverse effects that targeted therapies have on patients.
“There is no question that while targeted therapies have improved patient outcomes, they have chronic toxicity that can be a source of great angst for our patients,” Dr. Wood said in an interview with Cancer Therapy Advisor.
“Staving targeted therapies off for a period of time avoids periods of toxicity but doesn’t alter their effectiveness when and if the disease kinetics change.”
Dr. Wood called deferred systemic therapy for mRCC “a very reasonable approach in selected patients, where the kinetics of their disease growth are slow, their metastatic burden is low, and they are enjoying a good quality of life.”
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Daniel Cho, MD, of the NYU Langone Medical Center in New York, NY, said he believes clinicians should consider deferral of systemic therapy more frequently when deciding whether to prescribe currently available molecularly targeted therapies such as vascular endothelial growth factor receptor (VEGFR) antagonists and mammalian target of rapamycin (mTOR) inhibitors.
“There are data to support that the efficacy of these agents is similar whether treatment is delayed or started immediately,” Dr. Cho told Cancer Therapy Advisor.
Patient Selection Critical
Deferral of systemic therapy, he noted, has long been used as a management option by physicians caring for patients with mRCC.
“The available data clearly suggest that there is a subset of patients who can experience prolonged periods of relative disease stability in the absence of systemic therapy,” Dr. Cho said. “The critical issue is identifying the patients for whom this strategy would be most appropriate.”
It is clear that most clinicians prefer surgical management of oligometastatic RCC, but the decision to delay systemic therapy for patients with mRCC, which is not amenable to surgical resection, is not as clear-cut.
“In the past, this approach was likely utilized mostly for patients whose age or other medical comorbidities precluded systemic therapy or those patients with low volume, slow-growing metastatic disease,” he explained.
With the acceptance that systemic therapy with currently available molecularly targeted therapies (such as VEGFR antagonists and mTOR inhibitors) does not have curative potential for most patients, deferring such therapy in appropriately selected patients is certainly reasonable clinically.
This decision, however, becomes more complicated for immunotherapies such as high-dose interleukin-2 and possibly the more novel immunotherapies such as PD-1/PD-L1 antibodies (+/- CTLA4 antibodies), as these agents have the potential for inducing durable and complete responses.
“As there is speculation that RCC becomes more immunosuppressive over time, the assumption that immunotherapy may be equally effective irrespective of timing of treatment may not be correct,” Dr. Cho said.
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