TKI in Poor-Risk Advanced Renal Cell Carcinoma - Episode 2

Surgery for Poor-Risk Advanced Renal Cell Carcinoma

February 7, 2020

Earle Burgess, MD:In the current era the role for cytoreductive nephrectomy has recently changed. Prior to the report of the CARMENA trial at ASCO [the American Society of Clinical Oncology 2018 Annual Meeting, most patients who were considered surgically eligible would undergo a cytoreductive nephrectomy at the time of diagnosis if their primary tumor remained intact. This is based on older data from the cytokine era that suggested that cytoreductive nephrectomies would improve patient outcome.

However, with current agents that are available, we learned from the CARMENA trial last year that with TKI [tyrosine kinase inhibitor]-based therapy patients did not appear to benefit from initial cytoreductive nephrectomy. Specifically, in the CARMENA trial, this was a randomized phase III noninferiority study that compared the role of cytoreductive nephrectomy prior to sunitinib use versus initial sunitinib use. It was shown that the sunitinib-only arm was noninferior to the cytoreductive nephrectomy arm.

After these results became available, the role of cytoreductive nephrectomy became limited only to select patients. Based on an update reported at ASCO this year 2019, further evidence looking at subgroups suggested that the higher number of risk points conferred a poorer prognosis, and thus, cytoreductive nephrectomies really aren’t indicated, other than potentially patients with only 1 risk point and 1 sight of disease.

Looking at the case that we’ve discussed, this patient has poor-risk disease. It was clear from the CARMENA study that in the current era, cytoreductive nephrectomy wouldn’t typically be done.

I would point out though 2 things to put the CARMENA study in context. First point, this was based on sunitinib monotherapy. The standard of care has changed since the CARMENA trial has resulted such that we are now using immunotherapy, most frequently in the frontline setting. We don’t know whether we can extrapolate the results of the CARMENA trial to the current agents. The other thing to keep in mind is based on subgroup analysis of CARMENA, in the group that received frontline sunitinib and then developed a favorable response to therapy, it subsequently received a delayed nephrectomy. It appeared that they may actually benefit.

Although that specific scenario wasn’t tested in the CARMENA trial, it does raise the possibility that for patients who receive initial systemic therapy and benefit, that they may ultimately benefit from a delayed nephrectomy. For the case that we’ve discussed today, cytoreductive nephrectomy would not typically be done given the current era and available regimens.

Transcript edited for clarity.


Case: A 68-Year-Old Man With Poor-Risk RCC

A 68-year-old man presented with a 6-week history of painless intermittent hematuria, fatigue and a 7-lb weight loss.

H & P:

  • History of medically controlled hypertension and hypercholesterolemia
  • 30 pack/year smoking history, social alcohol use  
  • Thin, ill-appearing; able to meet activities of daily living but unable to work due to fatigue. He spends more than half the day active on his feet

Labs:

  • CBC: Hb 11.4 g/dL, corrected Calcium,11.2 mg/dL, WBC, PLT, LFT all WNL
  • BP: 134/92
  • Lipid panel: WNL
  • U/A: gross hematuria

Imaging:

  • CT scan of the chest/abdomen/pelvis showed a left-sided 8.7 (I believe he said 8cm) cm renal mass, para-aortic lymph nodes, and pulmonary metastases

Diagnosis:

  • Underwent radical left nephrectomy; found to have Fuhrman grade 4 clear cell carcinoma without sarcomatoid features
  • IMDC risk-score: poor

Treatment:

  • Initiated treatment with ipilimumab 1mg/kg IV + nivolumab 3mg/kg IV q3w for 4 doses; achieved partial response; received maintenance nivolumab for 6 doses (q4w) followed by disease progression
  • Patient was switched to cabozantinib 60mg PO qDay