Matthew T. Campbell, MD, MS

Matthew T. Campbell, MD, assistant professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses survival outcomes for patients with both metastatic renal cell carcinoma (RCC) and sarcomatoid dedifferentiation and how they each have evolved over the past few years.

According to Campbell, patients with clear cell RCC with sarcomatoid had a worse prognosis than patients diagnosed with clear cell alone. This was the same for patients with papillary sarcomatoid or those with sarcomatoid chromophobe.

In recent years, there has been a positive shift and a number of advances made for patients with RCC. Specifically, immunotherapy has shown to have benefits in this patient population.

Cambell also highlights the CheckMate-214 study (NCT02231749) of nivolumab (Opdivo) combined with ipilimumab (Yervoy) compared with sunitinib (Sutent) in patients with previously untreated advanced or metastatic renal cell carcinoma.

 These patients used to have the very worst prognosis of patients diagnosed with just about any histology. Clear cell with sarcomatoid did worse than the patients just with clear cell. Same with their counterparts with papillary sarcomatoid, [or] chromophobe sarcomatoid. They were, in a sense, more resistant to targeted therapy. However, we are seeing tremendous benefit with immunotherapy, and I would say that is the number 1 predictive biomarker of response to immune checkpoint therapy is the presence of sarcomatoid.

My partner at MD Anderson Cancer Center has presented data on how patients with sarcomatoid are treated with nivolumab and ipilimumab from the CheckMate-214 study. It was a subgroup, but the patients did extremely well, and the response rate of approximately 60% complete response rate pushing 20% was quite impressive. We are seeing that those patients with sarcomatoid features who are living longer may not be reaching the same bar that the rest of the clear cell population but significantly improving.

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Matthew T. Campbell, MD, discusses survival outcomes for patients with both metastatic renal cell carcinoma and sarcomatoid dedifferentiation and how they each have evolved over the past few years.

Survival Outcomes for Metastatic RCC and Sarcomatoid Dedifferentiation

Matthew T. Campbell, MD, assistant professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the results of a retrospective analysis of patients with metastatic renal cell carcinoma (mRCC) with sarcomatoid dedifferentiation.

Sarcomatoid dedifferentiation is associated with poor survival outcomes in patients with mRCC. Campbell and other investigators reviewed the cases of 48 patients who were treated with immune checkpoint inhibitors at MD Anderson Cancer Center, 41 of whom had clear cell RCC and 7 of whom had non-clear cell RCC.

overall response rate (ORR) among patients in the study

 was 35.4%, including 8 patients (16.7%) who had a complete response. There was a disease control rate of 52.0%. Only 1 patient with non-clear cell disease had a partial response. For the patients with clear cell RCC, the median progression-free survival (PFS) was 8.9 months and median overall survival (OS) was 30.1 months, though median PFS was only 2.3 months and median OS was 6.7 months for the patients with non-clear cell disease.

Campbell says that patients with sarcomatoid dedifferentiation are seeing improved outcomes with immunotherapy, and he feels that the immunotherapy combination of nivolumab (Opdivo) and ipilimumab (Yervoy) will offer the best efficacy for these patients despite potential toxicity.

The response rate for all patients that received immunotherapy with sarcomatoid dedifferentiation was around 35%. The chance of benefit for most patients was much higher, with fewer patients having frank progressive disease as best response. Again, PFS [was] somewhere around 9 to 10 months and OS right around 30 months. [It’s] single institution experience, but I think it again adds value from the fact that we are seeing more and more patients with sarcomatoid dedifferentiation with improved outcomes in this new era of immuno-oncology.

I think when I see patients in my clinic that have sarcomatoid dedifferentiation with metastatic disease, my preference is to use nivolumab and ipilimumab as initial therapy. I do this because I again think that these patients are more likely to respond to immunotherapy and tend to be more resistant to targeted therapy. I think these are patients that the risk of potential toxicity with nivolumab and ipilimumab is well warranted given the potential response and benefit.

Matthew T. Campbell, MD, discusses the results of a retrospective analysis of patients with metastatic renal cell carcinoma with sarcomatoid dedifferentiation.

RCC With Sarcomatoid Features May Benefit From Immunotherapy

Matthew T. Campbell, MD, assistant professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses the unmet needs for patients with RCC and sarcomatoid dedifferentiation.

According to Campbell, there are many unmet needs in the kidney cancer space in regard to both clear cell and non-clear cell RCC (ccRCC, nccRCC). A retrospective single-institution study conducted by MD Anderson Cancer Center examined 48 patients with RCC, 41 of which had sarcomatoid dedifferentiated ccRCC and 7 had sarcomatoid dedifferentiated nccRCC.

The study revealed that while ICI therapy was effective in patients with sarcomatoid dedifferentiated ccRCC, treating patients with nccRCC remains a challenge. More trials examining this patient population are needed to fully understand and provide patients with the best treatment options.

 There are a number of unmet needs. Currently, the most exploration has been done in clear cell kidney cancer, which is the most common kidney cancer, but we still have significant unmet needs in patients with non-clear cell kidney cancer. Far fewer trials have been done and far fewer trials are ongoing, and that's a patient population that we need to continue to focus on. We also struggle knowing optimal initial treatment for patients as well as optimal sequence for patients. We still have a tremendous way to go even though we are making substantial improvements.

 I think sites of disease and disease burden are large challenges. I'm particularly interested in bone metastasis. This is a site of disease that tends to cause a lot of pain and suffering, decreased response to treatment, oftentimes and increased risk of death. We also struggle with patients with extensive liver metastasis in brain metastasis, in addition to patients that are refractory to initial systemic treatment.

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Matthew T. Campbell, MD, discusses the unmet needs for patients with renal cell carcinoma and sarcomatoid dedifferentiation. 

Addressing Unmet Needs in Renal Cell Carcinoma

Matthew T. Campbell, MD, MS, assistant professor in the Department of Genitourinary Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discusses trials investigating cabozantinib (Cabometyx) in patients with renal cell carcinoma (RCC).

For patients with RCC that have aggressive disease, including those with extensive bone disease, especially in their spinal column, or extensive liver disease, physicians sometimes only have one chance to treat them. Campbell thinks the combination of nivolumab (Opdivo) and cabozantinib, which in now approved in advanced RCC, is a good fit for this patient population.

An important question in this space, which may be answered when the CONTACT-03 (NCT04338269) data are published, is how to best treat patients who have already progressed on immune-oncology treatment or pembrolizumab (Keytruda) plus axitinib (Inlyta). Campbell wonders if cabozantinib plus immunotherapy with atezolizumab (Tecentriq) will enhance patient’s long-term disease control versus using cabozantinib alone.

Another study of cabozantinib in RCC is COSMIC-313 (NCT03937219), which is looking at cabozantinib combined with nivolumab and ipilimumab (Yervoy) in previously untreated patients with advanced or metastatic RCC. This trial will show if the combination has the ability to achieve complete responses in patients and if it will improve the durability of response. This is an important study in this setting, according to Campbell.

Matthew T. Campbell, MD, MS, discusses trials investigating cabozantinib in patients with renal cell carcinoma.

Matthew T. Campbell, MD, MS | Authors

Articles

Survival Outcomes for Metastatic RCC and Sarcomatoid Dedifferentiation

RCC With Sarcomatoid Features May Benefit From Immunotherapy

Addressing Unmet Needs in Renal Cell Carcinoma

Upcoming Trials Show Promise With Cabozantinib in RCC