A 58-Year-Old Man With Advanced Renal Cell Carcinoma - Episode 2

Risk Stratification of Patients With Advanced RCC

September 22, 2020
Robert Alter, MD

Robert Alter, MD: Looking back at the case I just presented, I think an important point is to recognize, as a medical oncologist, that we are given the luxury of seeing our patients after they have been given their diagnoses, either pathologically or radiographically. I think a message to primary care physicians is that mild symptoms, in this situation fatigue and anorexia, warrant a work-up and investigation. And appropriately so in this case, an assessment should also include laboratory studies, which were normal in this case. Scans did reveal an asymptomatic renal mass. After the patient underwent nephrectomy, one has the opportunity to consider active surveillance, or at times, adjuvant systemic therapy.

Dating back to clinical trials 10 years ago, initially they looked at the first therapies we had—that being Nexavar [sorafenib] versus sunitinib versus placebo. The clinical trial yielded no benefits utilizing a TKI [tyrosine kinase inhibitor] therapy for 1 year after surgery. So, 2 therapies, pazopanib and axitinib, were compared to placebo. Both treatments were done individually, meaning axitinib versus placebo in one study and pazopanib versus placebo in the other study. And it wasn’t until the S-TRAC data were presented several years ago, looking at sunitinib in patients with high-risk features, including pathologic advanced disease, that use of 1 year of sunitinib therapy versus placebo was investigated in patients with high-risk advanced disease.

Despite the fact that it did meet its primary end point, there’s been a lot of hesitation in utilizing this therapy. I think there are concerns about the risks and benefits of utilizing Sutent [sunitinib] for 1 year—utilizing the schedule of 28 days of therapy followed by 14 days off for a total of 1 year. I think the discussion about the toxicities of therapy should be individualized between the physician and the patient, recognizing that in the adjuvant setting toxicities can potentially affect patients’ long-term quality of life. Again, despite the data demonstrating that the therapy is potentially beneficial, improving overall survival by 1.3 years, the concern about the toxicities of therapy would warrant a conversation between the patient and the physician.

In regard to patients with metastatic disease, once the patient is initially diagnosed, there are several factors that one takes into consideration when one considers the use of systemic therapy. The new NCCN [National Comprehensive Cancer Network] guidelines have now made it clear as to how we should approach this. I think the most important approach one should have upon meeting a patient with metastatic disease is assessing risk stratification. This dates back to the interferon era, utilizing the MSKCC [Memorial Sloan Kettering Cancer Center] parameters, looking at the time from diagnosis to metastases, performance status, calcium, LDH [lactate dehydrogenase], as well as hemoglobin.

And then more recently, Daniel Heng, MD, MPH, and the IMDC [International Metastatic Renal Cell Carcinoma Database Consortium] did utilize those parameters, but removed LDH and substituted white blood cell count and platelet count for that. They utilized a 6-parameter factor in risk stratification. I always tell other colleagues that this information is right in front of you, relatively upon the first visit. The only thing we may not have immediately is the calcium level data, but you definitely can utilize the performance status, time from diagnosis to metastases, and the CBC [complete blood count] results that are right in front of you.

Risk stratification is now part of the NCCN guidelines. As a matter of fact, a lot of the therapies we are now using as our first-line therapies for metastatic clear cell renal cell carcinoma are based on categorizing patients into favorable-risk categorization compared to intermediate- and poor-risk categorization. These classifications that the NCCN has updated in their guidelines are helpful, in regard to allowing physicians to use a data-driven approach when considering first-line therapies for patients with renal cell carcinoma.

The CheckMate 214 clinical trial was the first time we actually saw a potential benefit. We saw a difference in data utilizing a single-agent oral tyrosine kinase inhibitor versus a combination of immunotherapy. The clinical trial compared the use of ipilimumab and nivolumab versus sunitinib in patients with intermediate- and poor-risk categorization, as well as favorable-risk categorization. The data have been published for 3 to 4 years already. Most recently, Nizar Tannir, MD, presented the 42-month analysis.

In patients with intermediate- and poor-risk categorization, there was a significant improvement in response rates, overall survival, as well as complete responses in patients treated with ipilimumab and nivolumab. However, in the favorable-risk group, we saw that single-agent tyrosine kinase inhibition with sunitinib has continued to show a significant benefit compared to the combination of immunotherapies. And again, that is in the good-risk or favorable-risk category. Risk stratification should be done relatively early, because it can help determine how one should proceed in terms of first-line therapy for metastatic renal cell carcinoma.

Transcript edited for clarity.


Case: A 58-Year-Old Man With Advanced Renal Cell Carcinoma

  • August 2018: A 58-year-old man complained of fatigue and anorexia; after appropriate workup the patient was diagnosed with clear cell renal cell carcinoma
    • He underwent left total nephrectomy
  • March 2019: He developed metastatic disease to the lungs bilaterally (30 x 35 mm), mediastinum and soft tissue metastatic deposits
    • MSKCC risk status: intermediate
    • ECOG 1
    • He was started on pembrolizumab 200 mg IV every 21 days + axitinib 5 mg PO q2Days
  • September 2019: He developed progressive disease (45 x 50 mm); pulmonary lymph nodes increased in size and new mediastinal and hilar lymphadenopathy was noted
    • He was started on lenvatinib 18 mg PO qDay + everolimus 5 mg PO qDay
  • October 2019: Due to grade 1 diarrhea, reduced dose of lenvatinib to 14 mg PO qDay + everolimus 5 mg PO qDay
  • December 2019: Lesions reduced to 20 x 20 mm from September 2019; achieved partial response
  • January 2020: He remained on therapy with lenvatinib + everolimus