Case Analyses in Renal Cell Carcinoma - Episode 13

Case 3: A New Horizon in Adjuvant Therapy for RCC

Bradley McGregor, MD, reviews the case of a 62-year-old man with mRCC and the use of adjuvant therapy for RCC.

Robert Motzer, MD: Case No. 3 addresses a new horizon in adjuvant therapy for RCC [renal cell carcinoma] and will be presented by Dr Bradley McGregor.

Bradley McGregor, MD: We’ve had a great discussion about what to do in the metastatic setting, but our ultimate goal is to prevent more patients from getting to that stage. I want to start with this case right here. In March, a 62-year-old male came to the emergency department with hematuria, abdominal pain, weight loss, and fatigue. We know he does have a history of duodenal ulcer over 20 years ago for which he remains on a PPI [proton pump inhibitor], no current symptoms, an active smoking history, smoking 1 pack per day. He has hypertension that’s well controlled with medications with amlodipine and olmesartan.

On presentation...a hemoglobin of just under 11 g/dL, with ANC [absolute neutrophil count] of 7.4. Blood count normal at 316 and normal calcium. He undergoes an ultrasound, which shows a large abnormality in the left kidney, and subsequently undergoes a CT scan about a month later, which shows a large left-sided kidney mass, 8 by 6 by 7 cm, with concern for some associated lymphadenopathy in a relatively indeterminant subpleural nodule. He has an excellent performance status, and he’s presenting to talk about what the next options are.

Robert Motzer, MD: In terms of the management for a large locally extensive kidney tumor like this, Brad, what has been the mainstay of treatment for a patient like this?

Bradley McGregor, MD: This is going to involve a multidisciplinary discussion with your urology team, and this should really be done at an academic center where they have the clinical volume and expertise in managing these situations. We have excellent surgeons and we’ll discuss, is this surgery resectable? If the surgeon feels with the current volume of disease that this is something that can be surgically resected, I think that’s generally our preference to go to in the frontline setting.

But if we have a situation where there’s concern about resectability, now we have data that we can use perioperative therapy. We have data from…looking at axitinib. Also, more recently axitinib in this very situation, local invasion, where they showed of these patients treated with axitinib 5 mg twice daily for 8 weeks, while the response rate was just less 30%, 40% had a reduction in the extent of surgery at time of surgery with this perioperative therapy. Certainly, we know the No. 1 goal is R0 [no residual tumor] resection. Thus, if systemic therapy will improve those odds, I think it’s certainly something to consider. As we see with the axitinib data, no one had marked progressive where they weren’t able to get to surgery.

Robert Motzer, MD: A TKI [tyrosine kinase inhibitor] given before surgery was disappointing, right? Also, it didn’t seem to accomplish much. What about I/O [immuno-oncology] therapy as a neoadjuvant? Is this something that can be given outside of a trial? Are there specific trials that should be on our radar screen for this approach?

Bradley McGregor, MD: I think there have been some very fascinating early phase 2 data looking at NIVO/IPI [nivolumab/ipilimumab], potentially some VEGF/I-O. Also, we’ve seen some encouraging response rates. When we see response rates on TKI/I-O of 70% with LEN/PEMBRO [lenvatinib/pembrolizumab], it’s certainly intriguing that doing that duo combination up front may lead to better outcomes than we see with TKI monotherapy. We know from the SURTIME study data that perioperative TKI didn’t really affect surgical outcomes, and it seemed to be a safe strategy. Hence, I think certainly this is something that needs to be evaluated further.

Transcript edited for clarity.