medwireNews: The NeoAvAx trial has demonstrated encouraging response and disease-free survival (DFS) after neoadjuvant treatment with avelumab plus axitinib in people with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy.
Results from the phase 2 study investigating the immune checkpoint inhibitor (ICI) avelumab and the tyrosine kinase inhibitor (TKI) axitinib were presented by Axel Bex, from the Netherlands Cancer Institute in Amsterdam, at the 2022 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA.
Axel Bex outlines the reasoning behind the choice of tumor response as the primary endpoint for the NeoAvAx study of avelumab plus axitinib in the neoadjuvant high-risk renal cell carcinoma setting, and discusses the next steps (4:20).
Daniel Geynisman (Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA), who discussed the presentation, said that after seeing these data he “will feel more comfortable continuing to use [ICI]/TKI therapy in the neoadjuvant setting in highly select patients,” such as those with a solitary kidney or those with “unresectable disease that you are trying to make resectable.”
But noting that a previous study of neoadjuvant axitinib alone in the same setting showed a higher response rate than NeoAvAx, he wondered whether ICIs were needed at all in the presurgical setting. Geynisman suggested that ICIs likely do not have a role in tumor reduction, but may well be involved in developing long-term immunologic memory, although this is as yet unproven.
In the current study, 40 patients with locally advanced, high-risk RCC received up to 12 weeks of treatment with avelumab 10 mg/kg every 2 weeks alongside axitinib given twice a day at doses of 5–10 mg before undergoing surgery. Participants were aged a median of 63 years and the mean tumor diameter at baseline was 10.3 cm.
The primary endpoint of a partial response by RECIST criteria in the primary tumor was achieved by 30% of the participants, which was higher than the prespecified cutoff for success of 25%. And the majority (83%) of the 12 patients with a primary response were disease-free at the time of analysis.
At a median follow-up of 23.5 months, 13 (32.5%) patients experienced disease recurrence and three (7.5%) died. The median DFS and overall survival times had not been reached at data cutoff.
Bex noted that there was a difference in DFS between patients with and without a partial tumor response, favoring the former group, but the between-group difference did not reach statistical significance.
Reporting on the safety data, he said that “surgical adverse events [were] as expected in this patient population with locally advanced RCC and there were no new safety signals associated with this neoadjuvant approach.”
One patient underwent surgery at week 6 due to suspected tumor progression, although this turned out to be a biopsy-related hematoma, one developed systemic disease during neoadjuvant treatment, and a third patient’s surgery was delayed by 3 weeks due to grade 2 hypothyroidism.
Serious adverse events (AEs) occurred in 32.5% of study participants. Most were “attributable to either prolonged hospitalization or readmission, and only a minority related to trial procedures, and all of them resolved,” said Bex.
He added that treatment-related AEs were “as reported in the metastatic setting.” The most common AEs of grade 1 or 2 were hypertension (55.0%), infusion-related reactions (IRR; 55.0%), and fatigue (47.5%). There was one case each of grade 3 hypertension, IRR, fatigue, nausea, hand–foot syndrome, and elevated liver function tests, and no grade 4 or 5 events.
A total of 15% of patients needed a dose reduction of axitinib to 3 mg twice daily and 30% needed a dose interruption, but the presenter noted that these were “short-lived” and no patient discontinued the TKI.
With regard to avelumab, three (7.5%) patients had an interruption of one cycle and the same number discontinued, one each after three cycles due to an IRR of grade 3 and COVID-19, and one after five cycles due to grade 3 elevated liver function tests.
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