Exelixis announced positive top-line results from the primary analysis of METEOR, a Phase 3 trial comparing Cometriq (cabozantinib) to everolomus in patients with metastatic renal cell carcinoma (RCC) who have experienced disease progression following treatment with a VEGF receptor tyrosine kinase inhibitor (TKI).

METEOR is an open-label, event-driven trial that randomized 658 patients 1:1 to receive cabozantinib 60mg or everolimus 10mg. They were stratified based on the number of prior VEGF receptor TKI therapies received, and on commonly applied RCC risk criteria. No cross-over was allowed between the study arms. The primary endpoint was progression-free survival (PFS).

RELATED: Study on Opdivo for Renal Cell Carcinoma Halted Early

The trial met its primary endpoint of demonstrating a statistically significant increase in PFS in the first 375 randomized patients. Cabozantinib reduced the risk of disease progression or death by 42% compared to the everolimus arm (HR=0.58, 95% CI 0.45–0.75, P<0.0001).

Cometriq is already indicated for the treatment of progresive, metastatic medullary thyroid cancer (MTC).

For more information call (650) 837-7000 or visit Exelixis.com.

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Bristol Myers Squibb Company announced that CheckMate-025, a Phase 3 study investigating Opdivo (nivolumab) vs. everolimus in previously treated patients with advanced or metastatic renal cell carcinoma (RCC) was stopped early due to the primary endpoint being met.

The recommendation was made by the Independent Data Monitoring Committee (DMC) after determining that the study showed superior overall survival in patients receiving Opdivo compared to the control arm. CheckMate-025 is an open-label, randomized study of Opdivo vs. everolimus in previously-treated patients with advanced or metastatic clear-cell renal cell carcinoma. The trial randomized 821 patients to receive either nivolumab or everolimus until documented disease progression or unacceptable toxicity. The primary endpoint is overall survival.

RELATED: CRLX101 Fast Tracked for Metastatic Renal Cell Carcinoma

Bristol-Myers Squibb will inform all eligible patients of the opportunity to continue or start treatment with Opdivo in an open-label extension. The company will complete a full evaluation of the final CheckMate-025 data and work with investigators on the future presentation and publication of the results. M

Opdivo is already indicated for unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. It is also approved for metastatic squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.

For more information call (800) 321-1335 or visit BMS.com.

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Deferred systemic therapy is a reasonable option for selected patients with metastaticrenal cell carcinoma (mRCC), according to researchers. This approach may offer patients a better quality of life without negatively affecting survival.

Investigators at Duke University in Durham, NC, led by Daniel J. George, MD, reviewed data from 60 patients with mRCC who did not receive systemic therapy within the first year after diagnosis.¹

Patients had a median age of 61.2, and their median duration from diagnosis of localized RCC to development of mRCC was 41.9 months.

Of these patients, 36 (60%) were managed with surgical metastasectomy alone, 7 patients (12%) received multiple local treatment modalities, 8 patients (13%) underwent active surveillance, 4 patients (7%) were managed supportively, and 5 patients (8%) were categorized as “other.”

The cohort had a median follow-up of 52.9 months. The 3-year survival was 83% overall and 94% for patients who underwent surgical metastasectomy as the initial management strategy.

At 3 years, 49% of patients had no evidence of disease and 19% had died or been transitioned to hospice. The 5-year survival rate was 59%, and 24% still had no evidence of disease.

“Although the new targeted therapies for mRCC are better tolerated than systemic chemotherapies, they still have serious side effects,” the authors wrote. “Therefore, a strategy of delaying therapy may result in significant quality of life gains for these patients.”

In a discussion of study limitations, Dr. George's group pointed out that their cohort included only patients treated at a large academic medical center, so their sample may not be representative of all patients with mRCC or clinical environments because of sample bias and self-selection bias.

Mounting Evidence

The study adds to a growing body of evidence suggesting that deferred systemic therapy may be an attractive option for selected patients.¹

Investigators at the University of Ulsan College of Medicine in Seoul, South Korea, studied 58 patients with asymptomatic or minimally symptomatic mRCC placed on active surveillance.²

After a median follow-up of 31.4 months, the median time to progression (the primary endpoint of the study) was 12.4 months, and the median overall survival was not reached.

“Asymptomatic or minimally symptomatic mRCC patients can be observed for a prolonged period without active treatment,” the researchers concluded.

Dr. George's team cited a report showing that, in a trial of pazopanib for mRCC, researchers observed no difference in overall survival between patients started immediately on the drug and those started on placebo who then transitioned to pazopanib only after disease progression.³

In a separate retrospective study of 62 patients with mRCC with asymptomatic or slow progressive disease, British researchers found that a period of observation prior to starting first-line therapy did not adversely affect progression-free and overall survival.⁴

After an average of 18.7 months of observation, 39 patients started on sunitinib, 18 patients were treated with interferon, and 5 received other agents. The median progression-free survival (PFS) among patients receiving first-line therapy was 9 months.

It was also 9 months for the group of patients who received sunitinib and it was 6.7 months for interferon recipients.

Median overall survival—defined as the time from the start of first-line therapy to death—was 25.2 months for all patients, 17.4 months for the sunitinib-treated patients, and 37.6 months for patients in the interferon group.

The authors stated that the median PFS and overall survival times were comparable to those observed in the pivotal phase 3 and expanded access trials of sunitinib.

Dr. George and his colleagues commented in their report, “In a time of quickly evolving treatment choices for patients with mRCC, it is critical that we understand treatment patterns and outcomes in routine clinical practice. The need to better understand the observed practice of delayed systemic therapy for patients with mRCC is such an example.”¹  

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Deferred systemic therapy is a reasonable option for selected patients with metastaticrenal cell carcinoma (mRCC), according to researchers. This approach may offer patients a better quality of life without negatively affecting survival.

Investigators at Duke University in Durham, NC, led by Daniel J. George, MD, reviewed data from 60 patients with mRCC who did not receive systemic therapy within the first year after diagnosis.¹

Patients had a median age of 61.2, and their median duration from diagnosis of localized RCC to development of mRCC was 41.9 months.

Of these patients, 36 (60%) were managed with surgical metastasectomy alone, 7 patients (12%) received multiple local treatment modalities, 8 patients (13%) underwent active surveillance, 4 patients (7%) were managed supportively, and 5 patients (8%) were categorized as “other.”

The cohort had a median follow-up of 52.9 months. The 3-year survival was 83% overall and 94% for patients who underwent surgical metastasectomy as the initial management strategy.

At 3 years, 49% of patients had no evidence of disease and 19% had died or been transitioned to hospice. The 5-year survival rate was 59%, and 24% still had no evidence of disease.

“Although the new targeted therapies for mRCC are better tolerated than systemic chemotherapies, they still have serious side effects,” the authors wrote. “Therefore, a strategy of delaying therapy may result in significant quality of life gains for these patients.”

In a discussion of study limitations, Dr. George's group pointed out that their cohort included only patients treated at a large academic medical center, so their sample may not be representative of all patients with mRCC or clinical environments because of sample bias and self-selection bias.

Mounting Evidence

The study adds to a growing body of evidence suggesting that deferred systemic therapy may be an attractive option for selected patients.¹

Investigators at the University of Ulsan College of Medicine in Seoul, South Korea, studied 58 patients with asymptomatic or minimally symptomatic mRCC placed on active surveillance.²

After a median follow-up of 31.4 months, the median time to progression (the primary endpoint of the study) was 12.4 months, and the median overall survival was not reached.

“Asymptomatic or minimally symptomatic mRCC patients can be observed for a prolonged period without active treatment,” the researchers concluded.

Dr. George's team cited a report showing that, in a trial of pazopanib for mRCC, researchers observed no difference in overall survival between patients started immediately on the drug and those started on placebo who then transitioned to pazopanib only after disease progression.³

In a separate retrospective study of 62 patients with mRCC with asymptomatic or slow progressive disease, British researchers found that a period of observation prior to starting first-line therapy did not adversely affect progression-free and overall survival.⁴

After an average of 18.7 months of observation, 39 patients started on sunitinib, 18 patients were treated with interferon, and 5 received other agents. The median progression-free survival (PFS) among patients receiving first-line therapy was 9 months.

It was also 9 months for the group of patients who received sunitinib and it was 6.7 months for interferon recipients.

Median overall survival—defined as the time from the start of first-line therapy to death—was 25.2 months for all patients, 17.4 months for the sunitinib-treated patients, and 37.6 months for patients in the interferon group.

The authors stated that the median PFS and overall survival times were comparable to those observed in the pivotal phase 3 and expanded access trials of sunitinib.

Dr. George and his colleagues commented in their report, “In a time of quickly evolving treatment choices for patients with mRCC, it is critical that we understand treatment patterns and outcomes in routine clinical practice. The need to better understand the observed practice of delayed systemic therapy for patients with mRCC is such an example.”¹  

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