Frontline Keytruda plus Lenvima for advanced renal cell carcinoma is an effective treatment with life-prolonging benefits, although patients should be monitored for side effects that can be easily managed.
Keytruda (pembrolizumab) plus Lenvima (lenvatinib) for the frontline treatment of adults with advanced renal cell carcinoma represents another strong treatment choice, although the decision should be made based on the benefits and risks posed by each option.
The Food and Drug Administration (FDA) approved this drug combination August of this year, adding another life-prolonging, first-line treatment regimen to the other guideline-recommended options: Yervoy (ipilimumab) plus Opdivo (nivolumab), Cabometyx (cabozantinib) plus Opdivo) and Keytruda plus Inlyta (axitinib).
“(Keytruda plus Lenvima) is another option,” Dr. Toni K. Choueiri, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute in Boston, told CURE®. “It did have though the longest (progression-free survival), and highest response rate and complete response rates as compared to other combinations, though not through a direct head-to-head comparison.”
“Those are the four choices now,” said Dr. Andrew J. Armstrong, professor of medicine, surgery, pharmacology and cancer biology at Duke University in Durham, North Carolina, in an interview with CURE®. “We never thought we’d have four choices.”
Choueiri said that this recent FDA approval “is an example, yet again, of combination therapies in advanced (renal cell carcinoma) being the rule, not the exception.”
Armstrong added that more than 15 years ago, the only available therapies adults with advanced renal cell carcinoma did not prolong life for these patients. Anti-angiogenic drugs, which block the growth of blood vessels that support tumor growth, became more standard of care approximately 15 years ago and were shown to prolong life and delay the time until disease progression. Immune checkpoint inhibitors, which rev up the immune system to attack cancer, have revolutionized how patients with advanced renal cell carcinoma are treated during the past five years.
“The exciting think about these immune therapies is now you can see patients go into remission, and then eventually even stop therapy and maintain that remission,” Armstrong said. “Our hope is that some of these remissions may result in a cure. Long-term, durable remissions, even off therapy, (have been) seen for many different cancers like melanoma, but which we’re hoping will turn out to be the case with long-term follow-up in kidney cancer.”
The recent FDA approval of Keytruda plus Lenvima was based on findings from the CLEAR trial, which demonstrated a 61% reduced risk of disease progression or death in patients treated with the combination therapy. The regimen also contributed to a progression-free survival of 23.9 months compared with 9.3 months in patients treated with Sutent (sunitinib).
Although the benefits of Keytruda plus Lenvima are evident, the combination treatment also comes with some risks, more so than single therapies. Keytruda, an immunotherapy, may cause shortness of breath, cough, rash, diarrhea, cold intolerance and fatigue.
“Doctors and patients need to be particularly attuned to these things because they’re readily reversible with steroids like prednisone,” Armstrong said. “These immune checkpoint inhibitors, that’s their power, that they can rev up the immune system to induce remissions, but also can cause these immune-related side effects.”
In addition, Lenvima, an oral targeted therapy, may be associated with its own side effects, especially at the 20-milligram dose given to patients in the CLEAR trial. Side effects from Lenvima in the trial led to a dose reductions, interruptions or discontinuations for large number of patients.
“We’ve learned from this cocktail that the combination is very effective, but the side effects of Lenvima, particular at the doses that they used in this CLEAR trial, are particularly concerning,” Armstrong said. “Even though there’s significant benefits in terms of survival and delaying progression, I think we have to manage patients very carefully with dose reductions and drug holds because of some of the side effects from (Lenvima), which can cause high blood pressure, fatigue, loss of appetite, diarrhea or stomach upset.”
Armstrong added that this emphasizes the importance of following patients carefully for potential side effects and to be flexible with dosing to find the right dose for that patient, allowing for personalized care.
Choueiri mentioned, “It is a great time for the field of (renal cell carcinoma). What an honor and privilege to see these advances impacting the lives of patients.”
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