Brian I. Rini, MD

Brian I. Rini, MD, professor of medicine and inaugural chief of Clinical Trials at Vanderbilt-Ingram Cancer Center, discusses the benefits of long-term follow-up for trials and the results from 42-month follow-up of the KEYNOTE-426 study (NCT02853331) of pembrolizumab (Keytruda) plus axitinib (Inlyta) versus sunitinib (Sutent) as first-line therapy for patients with advanced clear cell renal cell carcinoma (RCC).

The data for KEYNOTE-426 presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting were from the second long-term follow-up of this trial. Long-term follow-up is important for combination therapies especially, according to Rini. The other main combination therapy in RCC is nivolumab (Opdivo) plus ipilimumab (Yervoy). The trial for that combination has longer follow-up than pembrolizumab plus axitinib because it was conducted before KEYNOTE-426. Rini says the long follow-up, duration of response, and durability are important.

The 2021 ASCO data had a minimum of 3 years follow-up and a median of 3.5 years. Rini says this is not quite long term, but it’s starting to get to that range to see how durable responses will be. Pembrolizumab was given for 35 doses or 2 years. An important question for this trial is how durable responses will be after stopping pembrolizumab; knowing the required duration of therapy will be vital to know going forward. Once there are longer-term outcomes, the data can be compared with other regimens in RCC as well.

The updated KEYNOTE-426 data have shown it is a standard of care in RCC and the efficacy has held up over time. There were advantages in overall survival, progression-free survival, overall response rates, and complete response rates for patients receiving the combination versus sunitinib. Those benefits have continued even after pembrolizumab was stopped. Although there is still more work to be done, these updates are encouraging, according to Rini.

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Brian I. Rini, MD, discusses the benefits of long-term follow-up for trials and the results from 42-month follow-up of the KEYNOTE-426 study of pembrolizumab plus axitinib versus sunitinib as first-line therapy for patients with advanced clear cell renal cell carcinoma.

Follow-Up Shows Continued Efficacy in RCC With Pembrolizumab/Axitinib

Brian I. Rini, MD, professor of medicine and inaugural chief of Clinical Trials at Vanderbilt-Ingram Cancer Center, discusses the dosing of nivolumab (Opdivo) plus ipilimumab (Yervoy) for patients with renal cell carcinoma.

An abstract presented at the 2020 International Kidney Cancer Symposium (IKCS) looked at lowering the dosing of nivolumab and ipilimumab as a novel strategy for treating this patient population. Rini says the some of the early efficacy data released in the abstract suggested the lower dose of the combination was not as active as the dosing used in CheckMate 214 (NCT02231749).

In clinical practice, most physicians adjust doses as needed, but should be mindful of the balance of efficacy and toxicity, according to Rini. Treatment needs to be tolerable, but physicians should also be trying to get the best efficacy, especially in the first-line setting. Patients can have durable responses with nivolumab and ipilimumab and as this combination and other RCC combinations continue to be developed, questions on dosing, when to stop the drugs, and which patients require more aggressive or less aggressive treatment will have to be investigated. Rini is particularly interested in the effects of intensifying treatment in patients who need it and de-intensifying in patients who do not. That has no been researched in this setting yet.

Brian I. Rini, MD, discusses the dosing of nivolumab plus ipilimumab for patients with renal cell carcinoma.

Lower Dosing of Nivo/Ipi Less Effective Than CheckMate 214 Dosing in RCC

Brian I. Rini, MD, professor of medicine at the Cleveland Clinic, discusses how data should be looked at between 2 combinations for the treatment of renal cell carcinoma (RCC). He says atezolizumab (Tecentriq) plus bevacizumab (Avastin) will never be compared head to head with ipilimumab (Yervoy) plus nivolumab (Opdivo).

Having these 2 combinations is great from a clinician standpoint as they are additional options for patients with RCC. One combination could be more tolerable and suitable for some patients than the other combination, Rini says. It is the clinician&rsquo;s job to then figure out which combination is best.

Brian I. Rini, MD, professor of medicine at the Cleveland Clinic, discusses how data should be looked at between 2 combinations for the treatment of renal cell carcinoma. He says atezolizumab plus bevacizumab will never be compared head to head with ipilimumab plus nivolumab.

Selecting Atezolizumab Plus Bevacizumab Versus Ipilimumab Plus Nivolumab in RCC

Brian I. Rini, MD, professor of medicine at the Cleveland Clinic, discusses the rationale for combining atezolizumab (Tecentriq) and bevacizumab (Avastin) for patients with metastatic renal cell carcinoma (mRCC) in the IMmotion151trial.

Both of these agents have proven to be active as monotherapies, and as such, it seemed rational to combine them. Additionally, VEGF has immune-suppressive effects, including promoting myeloid-derived suppressor cells, regulatory T cells, etc. By suppressing VEGF, the microenvironment is more favorable for the immunotherapy to act.

Brian I. Rini, MD, professor of medicine at the Cleveland Clinic, discusses the rationale for combining atezolizumab and bevacizumab for patients with metastatic renal cell carcinoma in the&nbsp;IMmotion151trial.

Brian I. Rini, MD | Authors

Articles

Follow-Up Shows Continued Efficacy in RCC With Pembrolizumab/Axitinib

Lower Dosing of Nivo/Ipi Less Effective Than CheckMate 214 Dosing in RCC

Selecting Atezolizumab Plus Bevacizumab Versus Ipilimumab Plus Nivolumab in RCC

Rationale for Combining Atezolizumab/Bevacizumab in mRCC