RCC Care Continues to Evolve as the COVID-19 Crisis Rages On

The novel coronavirus disease (COVID-19) continues to impact the care of patients with metastatic renal cell carcinoma (mRCC) and other cancers in a multitude of ways, according to Toni K. Choueiri, MD, but those working in the field of oncology are rising up to the challenge by learning as much as possible about the virus to make the best treatment decisions possible for their patients.

Among the substantial efforts that are being made in light of the crisis is the COVID-19 and Cancer Consortium (CCC19), which is a multi-institutional registry designed to capture data on patients with cancer who have either suspected or confirmed infection with the virus. With the registry, health care professionals are provided with a platform where they can compile and collect key information to understand trends that might potentially impact treatment.

Data from the effort that were recently published in Cancer Discovery revealed several insights, including that hydroxychloroquine combined with any other agent was linked with increased mortality versus other COVID-19 therapies. Moreover, treatment with remdesivir (Veklury) was shown to result in reduced mortality versus untreated controls, although that was not determined to be statistically significant. Moreover, African American patients were half as likely to receive remdesivir than their white counterparts.

“[In light of the pandemic, many of us continue to try to adjust. We don't always get it right and we don't always agree, but at least we are flexible and we want to hear what others have to say [with regard to cancer care]; there are no right or wrong answers,” said Choueiri, who is the director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center, and senior physician with Dana-Farber Cancer Institute.

“It's a discussion at the end of the day, and at the heart of every discussion [is the question]: How can we continue to optimize treatment? Also, how can we reduce patient and staff exposure to the virus without compromising care?” he added. “It is a thin balance that we must adjust to every day. The name of the game is flexibility and all hands are on deck.”

In an interview with OncLive during the 2020 International Perspectives in Cancer webinar on GenitourinaryCancers, Choueiri, who is also the Jerome and Nancy Kohlberg Chair and professor of medicine with Harvard Medical School, further discussed the effect of the COVID-19 pandemic on cancer care, as well as key updates from the CCC19.

OncLive: Could you provide a small snapshot of the recent advances that have been made in mRCC management?

Choueiri: We're entering an era of combination therapies where single-agent TKIs are being given less and less often. We have [had several] FDA-approved regimens in the past couple of years, such as nivolumab (Opdivo) and ipilimumab (Yervoy), but also axitinib (Inlyta) in combination with the PD-1 inhibitor pembrolizumab (Keytruda), or the PD-L1 inhibitor avelumab (Bavencio). We also have the single-agent TKI cabozantinib (Cabometyx) that also showed superiority over sunitinib (Sutent) in the randomized, [phase 2] CABOSUN trial. These are most of the therapies available in metastatic disease. [The paradigm] is still evolving because some trials have finished accrual and are just about to be read-out; thus, more options may be added to this list [in the near future].

How does the COVID-19 pandemic impacted the diagnosis and treatment of these patients?

Many factors [impact care right now. For example, we debate treatment for [those with] small kidney masses. We are carefully delaying therapies over surgery. Situations also exist where we give cytotoxic chemotherapy, but not necessarily where we're pushing more growth factor [use], because we cannot afford [patients developing] neutropenic fever and being admitted to the hospital in this situation. We're reconsidering some of the neoadjuvant and adjuvant therapies [we utilize], as well as some clinical trials. We have a document that we put together at the Lank Center for Genitourinary Cancer with our Brigham and Women's Hospital colleagues, as well as our Dana-Farber colleagues which suggests a couple of [recommendations] on what to do during the pandemic. It's a dynamic document that we try to update every couple of months, depending on the number of cases.

This is a document focused on the management [of cancer] in terms of treatment [guidance]. For example, a patient with testicular cancer may need chemotherapy [and we will give them] chemotherapy; these are [treatments with] curative intent. However, if a patient with RCC is on their fourth, fifth, or sixth line of treatment, with limited therapies [available], perhaps we can discuss other options, such as adjuvant therapy. Would they be eligible for sunitinib or other [options]? This is how we try to provide the best care with the best evidence available for minimizing exposure [to COVID-19].

You are on the steering committee of the CCC19. Could you speak to the goal of this effort?

The CCC19 [was the product of] a group of curious investigators who met online through social media at the beginning of the pandemic and they started collecting clinical data and outcomes on patients with cancer who also had COVID-19. To date, we have over 100 sites that are entering patient data with regard to mortality, intensive care unit admission, and other variables.

The coordinating center is Vanderbilt University Medical Center with Jeremy L. Warner, MD, MS, and many other [oncologists] are on the steering committee. A couple interesting observations [from this effort] were presented during the 2020 ASCO Virtual Scientific Program, as well as [published in] Lancet and, most recently, in Cancer Discovery.

We're trying to identify a pattern of risk factors for patients with cancer. For example, for a patient who receives therapy and progresses, [we know that] their 30-day mortality is worse. Sometimes things end up [being] counterintuitive. It's an important database that now has information for thousands of patients. With the pandemic continuing to progress, we'll have more data coming out of CCC19 in the future.

Were any updates recently presented that you wanted to highlight?

An overall update with CCC19 was published in Cancer Discovery and this included more patients and more follow-up; it was also an update on risk factors. Compared with what we saw in the Lancet publication during the 2020 ASCO Virtual Scientific Program, no major differences were observed. The effort was led by Donna Rivera, PharmD, MSc, of the National Cancer Institute, as well as Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois and the president of ESMO.

We saw interesting patterns with [certain agents], such as hydroxychloroquine, which was associated with increased mortality. We had data on remdesivir, which was associated with reduced mortality, but this did not reach statistical significance. We saw that black patients were half as likely to receive remdesivir than white patients.

These are all observational studies; they are limited by potential unmeasured confounding but they add in aggregate to the emerging understanding of the pattern of care for patients with cancer and COVID-19. Hopefully, another larger update will be shared during the 2020 ESMO Virtual Congress, as we have some potential data that can be presented there.

What challenges remain with regard to COVID-19 and cancer care?

This isn't specific to patients with kidney cancer, but if a patient with cancer has active COVID-19, [the question arises as to whether] steroids will be associated with worse mortality. The data are all over the place. Recently, a reduced mortality has been seen with dexamethasone in sick patients with COVID-19. What does that mean for [those who] are not sick enough?

Overall, in patients with kidney cancer, the changes [that need to be made to the management of their disease] are logical ones. Someone with a complete response (CR) [can potentially] come to the hospital less and scans that were [once] scheduled for every 3 months can now be done every 4 to 6 months [instead].

If the patient is tolerating treatment well, does not need to come in, and they have a CR, could we interrupt the treatment for a while? When considering patients who are receiving oral TKIs, they don't need to come to the hospital because it’s easier; however, eventually they will. We have implemented some changes during the pandemic and have since relaxed now that we're entering into phases where we are finding that we can do things more normally. However, that could change tomorrow, based on the number of cases reported in our state and our hospital.

We're not in control. My message here is that the only thing in control [right now] is the virus. We are reactive. The virus dictates treatment. If we experience a second wave or a surge tomorrow, we will need to escalate to more aggressive measures. If suddenly, things get better and we [develop] a vaccine, we're going to go back [to normal] gradually. We'll see how the virus [progresses]. That's why I follow the cases of COVID-19 in our hospital, in our county, and in our state on a daily basis.

Reference:

Rivera DR, Peters S, Panagiotou OA, et al. Utilization of COVID-19 treatments and clinical outcomes among patients with cancer: a COVID-19 and Cancer Consortium (CCC19) cohort study [published online ahead of print July 22, 2020]. Cancer Discov. doi:10.1158/2159-8290.CD-20-0941