Advanced RCC: Prognosis and Therapy Selection

Chung-Han Lee, MD: In thinking about the patient’s prognosis at diagnosis; she presented with stage III disease. Most people with stage III disease probably have about a 50% chance of developing metastatic disease. What that means is 50% of patients are likely cured by a surgical resection alone. Unfortunately, for people who develop metastatic disease, the treatments we have today are mostly thought of as slowing the disease. Certainly we do risk stratification, that gives us a better idea of what their prognosis is. With some of the newer therapies, we are seeing an extension of that. A lot of that is changed by how they respond to the various agents.

There are multiple risk stratification schemes for the treatment of metastatic kidney cancer. The 2 most commonly used risk stratification systems are IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] and MSKCC [Memorial Sloan Kettering Cancer Center] risk scores. There are a lot of common features between those, as both were developed in the TKI [tyrosine kinase inhibitor]-targeted therapy or the interferon eras. They include things like performance status, hemoglobin, calcium, LDH [lactate dehydrogenase], and neutrophil count. The risk stratifications are slightly different between the two, but there’s significant overlap in how the patients end up being classified.

Some of the considerations that we have in terms of management and treatment are thinking about a lot of the different risk factors patients may have. In terms of age and fitness and underlying comorbidities, this is kind of the baseline status for the patient, and it gives you a sense of what treatments they may or may not tolerate. It also gives you a sense of what types of treatments may be associated with increased adverse effects related to that therapy. We also do risk stratification, which gives us an idea about the overall prognosis of the patient. These risk stratification schemes were developed even in times in which patients do not necessarily have very many effective therapies, so it gives you an idea of what the pace of disease may end up being. This has been further validated even in the era of having active systemic therapies. So that overall risk stratification has been very useful from a prognostic standpoint.

Now that we talk about first-line therapy, risk stratification has become more useful in that certain treatment types are a little bit different depending on clinical risk stratification. Not actually incorporated into risk stratification though are things like disease burden and the number of sites of metastases. These give you an idea of what type of response you may end up needing. For people who have high disease burden and multiple sites of metastatic disease, even if they don’t necessarily fall within the poor-risk stratification groups, it does make you a little bit more worried about them, and it changes the way you think about what systemic therapies you would necessarily try.

The other thing that we often take into consideration is the use of an I-O agent, or immunotherapy agent, versus a targeted therapy or thinking about combinations. Generally speaking, immunotherapies are well tolerated. However, the toxicity profile tends to be a little bit less predictable and less dose dependent. When you think about a TKI therapy, more patients end up having some sort of toxicity related to the medication. However, there is probably a dose dependence on that type of treatment. We notice improvements in the toxicities with just withdrawal of the medication or lowering of the dose.

There is some consideration that we also make with regard to using an oral versus an IV [intravenous] agent, and some of that is more of a logistical thing and patient preference. Often we have to inform the patient that because it’s oral doesn’t mean it’s easier to tolerate, or if it’s IV, it doesn’t mean that it works better. They’re completely different, and this is based off of the way the drugs were formulated.

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