Initial Management of Advanced RCC

Chung-Han Lee, MD: For the initial management of patients with localized renal cell carcinoma, the standard of care at this time remains surgical therapy, if possible. There has been a lot of investigation with regard to whether doing neoadjuvant therapy or even adjuvant therapy can be beneficial.

There is the option of using adjuvant sunitinib for the treatment after surgery for patients who are at risk high risk of recurrence. This is a medication that is FDA approved, and there’s a pretty extensive discussion with the medical oncologist with regard to the risk and benefits of using such an approach. Even though this is an FDA-approved regimen, it also has to be understood in the context of the other trials with other agents that are studied in that setting. This is often a very deep and intense conversation and has to be individualized.

In patients who ultimately develop metastatic disease, one of the things that has become standard of care is clinical risk stratification. Dividing patients into people who are favorable risk or intermediate or poor risk. This has guided the various treatment regimens. A lot of the risk stratification did come from the initial clinical trial of CheckMate 214, in which patients who had intermediate- and poor-risk disease did better on the combination of ipilimumab plus nivolumab compared to sunitinib. From a progression-free survival standpoint in subgroup analyses, the reverse seemed to be true. The initial FDA approval for the IPI/NIVO [ipilimumab plus nivolumab] combination was in intermediate- and poor-risk disease.

As per NCCN [National Comprehensive Cancer Network] guidelines, there’s a multitude of potential things that we can do in the first-line setting. Part of it is dependent on risk stratification and patient preferences. The combination of IPI/NIVO is of course approved in patients who have intermediate- or poor-risk disease. The combination with various TKI [tyrosine kinase inhibitor] and I-O immunotherapy agents are also FDA approved across all risk categories, and in certain groups, single-agent TKIs may also make sense for them.

Transcript edited for clarity.

Case Overview:

Initial presentation

• A 69-year-old woman presents with a 2-month history of fatigue, lower back pain and unintentional weight loss
• PMH: DM medically controlled
• PE: flank and lower back discomfort on palpation

Clinical workup

• Chest/abdominal/pelvic CT showed a right-sided 7.9 cm renal mass; paraaortic lymph node involvement
• Percutaneous biopsy confirmed clear cell renal cell carcinoma

Treatment and follow-up

• The patient underwent right total nephrectomy; surgery was well-tolerated
  • Follow-up at 3, 9, 12 months were unremarkable
• At 24 months the patient developed disease with multifocal disease in her lungs; Stage IV
• Labs within normal limits
• ECOG 0; good risk disease by IMDC and MSKCC risk
• She started treatment on pazopanib; well-tolerated, achieved PR
• 2 year later the patient suffered progression of disease; with increasing lung nodules, largest (30 mm)
• Lenvatinib 18 mg PO QD + everolimus 5 mg PO QD was initiated
  • Imaging at week 8 showed a 33% reduction from baseline of the largest lung lesion (20 mm);
  • At week 24 of treatment showed 40% reduction from baseline of largest lung lesion (18 mm); decrease in size of other pulmonary lesions noted
  • At 6 months she continued to have stable disease
  • At 12 months of treatment CT showed 2 new liver nodules