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First-line treatment for metastatic renal cell carcinoma evolving, but biomarkers still lacking

NEW YORK — First-line treatment of patients with metastatic renal cell carcinoma has evolved considerably in the past 18 months with FDA approval of cabozantinib monotherapy and the combination of ipilimumab and nivolumab.

Results of several other trials released over the past year offered additional valuable insights for first-line therapy, according to a presenter at HemOnc Today New York.

Molecular biomarkers are not yet ready for “prime time,” but they offer hope that precision medicine will be possible for this patient population, Petros Grivas, MD, PhD, medical director of the genitourinary cancers program at University of Washington and associate member of the clinical research division at Fred Hutchinson Cancer Research Center, said during his presentation.

It is important that clinical trials continue for every line of treatment because it is unlikely patients will be cured with current therapies, Grivas added.

“First-line therapy is good and frequently evolving... but we don’t have good biomarkers and we don’t have any clear action for best sequential therapy,” Grivas said. “We have to work stronger and better to find biomarkers.”

In 2016, the FDA approved cabozantinib (Cabometyx, Exelixis) for treatment of patients with advanced renal cell carcinoma who received prior anti-angiogenic therapy. A year later, the agency expanded approval of the agent to include first-line treatment of patients with advanced renal cell carcinoma.

In April 2018, the FDA approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) for intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma.

The agency based the approval on results of the randomized phase 3 CheckMate 214 trial. After a minimum follow-up of 17.5 months, resulted showed patients assigned nivolumab-ipilimumab achieved improved median OS (not reached vs. 26 months; HR = 0.63; P < .001), a higher overall response rate (42% vs. 27%; P < .001) and longer median PFS (11.6 months vs. 8.4 months) than those assigned sunitinib (Sutent, Pfizer).

The benefits of nivolumab and ipilimumab persisted at 30-month follow-up.

Grivas reviewed results from several other trials that evaluated additional potential first-line regimens.

Results from the randomized, phase 3 KEYNOTE 427 trial released last year showed pembrolizumab (Keytruda, Merck) monotherapy as first-line treatment induced an

overall response among 38.2% (95% CI, 29.1-47.9) of patients with clear-cell renal cell carcinoma. Researchers observed the benefit across International Metastatic RCC Database Consortium (IMDC) risk groups.

In February, results from the phase 3 JAVELIN Renal 101 trial demonstrated that the combination of avelumab (Bavencio; EMD Serono, Pfizer) and axitinib (Inlyta, Pfizer) extended PFS and increased objective response rates compared with sunitinib among patients with previously untreated advanced renal cell carcinoma. The results persisted among several prespecified subgroups, including patients with intermediate-risk disease and those with poor IMDC prognostic risk.

Also in February, results from the randomized phase 3 KEYNOTE 426 trial demonstrated the combination of pembrolizumab and axitinib extended OS and PFS compared with sunitinib as first-line treatment for patients with previously untreated advanced or metastatic clear-cell renal cell carcinoma.

Patients assigned pembrolizumab-axitinib appeared more likely than those assigned sunitinib to achieve 12-months OS (89.9% vs. 78.3%) and 18-month OS (82.3% vs. 72.1%).

Median OS had not been reached in either cohort, but results showed a significant improvement in OS with pembrolizumab-axitinib (HR = 0.53; 95% CI, 0.38-0.74). Patients assigned the combination also achieved significantly longer median PFS (15.1 months vs. 11.1 months; HR = 0.69; 95% CI, 0.57-0.84).

“I think we are all waiting to see what the FDA will do [with these combinations],” Grivas said. “They are not approved yet but I think, based on the data, it is very likely they will be.” – by John DeRosier

 

Reference:

Grivas P. Newly diagnosed metastatic renal cell carcinoma: Immunotherapy or targeted therapy? Presented at: HemOnc Today New York; March 21-23, 2018; New York.

Escudier B. N Engl J Med. 2019;doi:10.1056/NEJMe1900887.

McDermott DF, et al. Abstract 4500. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Motzer RJ, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1816047.

Powles T, et al. Abstract 543. Presented at Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.

Tannir NM, et al. Abstract 547. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.

 

Disclosure: Grivas reports financial relationships with AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Driver Inc., EMD Serono, Heron Therapeutics, Janssen, Merck, Pfizer and QED Therapeutics.

NEW YORK — First-line treatment of patients with metastatic renal cell carcinoma has evolved considerably in the past 18 months with FDA approval of cabozantinib monotherapy and the combination of ipilimumab and nivolumab.

Results of several other trials released over the past year offered additional valuable insights for first-line therapy, according to a presenter at HemOnc Today New York.

Molecular biomarkers are not yet ready for “prime time,” but they offer hope that precision medicine will be possible for this patient population, Petros Grivas, MD, PhD, medical director of the genitourinary cancers program at University of Washington and associate member of the clinical research division at Fred Hutchinson Cancer Research Center, said during his presentation.

It is important that clinical trials continue for every line of treatment because it is unlikely patients will be cured with current therapies, Grivas added.

“First-line therapy is good and frequently evolving... but we don’t have good biomarkers and we don’t have any clear action for best sequential therapy,” Grivas said. “We have to work stronger and better to find biomarkers.”

In 2016, the FDA approved cabozantinib (Cabometyx, Exelixis) for treatment of patients with advanced renal cell carcinoma who received prior anti-angiogenic therapy. A year later, the agency expanded approval of the agent to include first-line treatment of patients with advanced renal cell carcinoma.

In April 2018, the FDA approved the combination of nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) for intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma.

The agency based the approval on results of the randomized phase 3 CheckMate 214 trial. After a minimum follow-up of 17.5 months, resulted showed patients assigned nivolumab-ipilimumab achieved improved median OS (not reached vs. 26 months; HR = 0.63; P < .001), a higher overall response rate (42% vs. 27%; P < .001) and longer median PFS (11.6 months vs. 8.4 months) than those assigned sunitinib (Sutent, Pfizer).

The benefits of nivolumab and ipilimumab persisted at 30-month follow-up.

Grivas reviewed results from several other trials that evaluated additional potential first-line regimens.

Results from the randomized, phase 3 KEYNOTE 427 trial released last year showed pembrolizumab (Keytruda, Merck) monotherapy as first-line treatment induced an

overall response among 38.2% (95% CI, 29.1-47.9) of patients with clear-cell renal cell carcinoma. Researchers observed the benefit across International Metastatic RCC Database Consortium (IMDC) risk groups.

In February, results from the phase 3 JAVELIN Renal 101 trial demonstrated that the combination of avelumab (Bavencio; EMD Serono, Pfizer) and axitinib (Inlyta, Pfizer) extended PFS and increased objective response rates compared with sunitinib among patients with previously untreated advanced renal cell carcinoma. The results persisted among several prespecified subgroups, including patients with intermediate-risk disease and those with poor IMDC prognostic risk.

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Also in February, results from the randomized phase 3 KEYNOTE 426 trial demonstrated the combination of pembrolizumab and axitinib extended OS and PFS compared with sunitinib as first-line treatment for patients with previously untreated advanced or metastatic clear-cell renal cell carcinoma.

Patients assigned pembrolizumab-axitinib appeared more likely than those assigned sunitinib to achieve 12-months OS (89.9% vs. 78.3%) and 18-month OS (82.3% vs. 72.1%).

Median OS had not been reached in either cohort, but results showed a significant improvement in OS with pembrolizumab-axitinib (HR = 0.53; 95% CI, 0.38-0.74). Patients assigned the combination also achieved significantly longer median PFS (15.1 months vs. 11.1 months; HR = 0.69; 95% CI, 0.57-0.84).

“I think we are all waiting to see what the FDA will do [with these combinations],” Grivas said. “They are not approved yet but I think, based on the data, it is very likely they will be.” – by John DeRosier

 

Reference:

Grivas P. Newly diagnosed metastatic renal cell carcinoma: Immunotherapy or targeted therapy? Presented at: HemOnc Today New York; March 21-23, 2018; New York.

Escudier B. N Engl J Med. 2019;doi:10.1056/NEJMe1900887.

McDermott DF, et al. Abstract 4500. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Motzer RJ, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1816047.

Powles T, et al. Abstract 543. Presented at Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.

Tannir NM, et al. Abstract 547. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.

 

Disclosure: Grivas reports financial relationships with AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Driver Inc., EMD Serono, Heron Therapeutics, Janssen, Merck, Pfizer and QED Therapeutics.

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