Cabozantinib Plus Atezolizumab Delays Progression in mCRPC

SAN FRANCISCO — In patients with metastatic castration-resistant prostate most cancers (mCRPC) whose disease advanced on a contemporary hormonal therapy, the combination of cabozantinib (Cabometyx) plus atezolizumab (Tecentriq) improved radiographic development-free survival (rPFS) versus a switch to a second hormonal agent, a segment III trial confirmed.

The so-called CONTACT-02 glance incorporated patients with extrapelvic nodal or visceral metastasis with disease development after both abiraterone (Zytiga) or enzalutamide (Xtandi).

Median rPFS reached 6.3 months for patients assigned to cabozantinib-atezolizumab versus 4.2 months for these switched to the opposite hormonal agent (HR 0.65, 95% CI 0.50-0.84, P=0.0007), a “clinically meaningful state,” in accordance with Neeraj Agarwal, MD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake Metropolis, who supplied the findings here.

A construction for total survival (OS) most authorized the cabozantinib-atezolizumab arm (16.7 vs 14.6 months, respectively; HR 0.79, 95% CI 0.58-1.07, P=0.13), despite the incontrovertible truth that these data had been immature at the time of the prognosis, he reported at the Genitourinary Cancers Symposium.

That is the first segment III glance of a tyrosine kinase inhibitor (TKI) plus immune checkpoint inhibitor (ICI) aggregate to cloak a most well-known PFS state in mCRPC, acknowledged Agarwal, who added that the info toughen cabozantinib-atezolizumab as a doable new remedy possibility for a population with a extraordinarily heart-broken prognosis.

On the opposite hand, invited-discussant Kim N. Chi, MD, of the British Columbia Cancer Company in Vancouver, acknowledged he in my belief may possibly even no longer point out the mix, “given the info that we enjoy viewed and the easier alternatives which would be on hand for this patient population.”

Chi called the rPFS succor supreme modest and cited a bunch of glance barriers, including an absence of clarity on the explicit contribution of cabozantinib and atezolizumab. “Assemble no longer neglect that cabozantinib monotherapy had an rPFS succor previously described of 6.6 months in a more carefully pretreated population,” he acknowledged.

Attach watch over Arm Puzzled

Chi furthermore puzzled the numerous of decide watch over arm, asserting that an androgen receptor pathway inhibitor (ARPI) switch is “no longer the proper neatly-liked of admire this patient population with measurable disease and 40% visceral metastases.”

“There are better alternatives,” he acknowledged, noting that docetaxel and cabazitaxel enjoy shown PFS rates of 8-9 months in segment III trials.

Agarwal acknowledged chemotherapy use is mostly restricted in this patient population as a consequence of concerns about toxicity, frailty, and patient need, nevertheless.

When asked how investigators selected the decide watch over arm for the trial, he eminent that staunch-world study enjoy shown that mCRPC patients are less at possibility of settle for chemotherapy, and that contemporary hormonal therapy (NHT; i.e., ARPIs) has by no methodology been tested in opposition to docetaxel in a randomized managed trial after NHT failure. “Based on these two components, regulatory our bodies all around the enviornment enjoy permitted various NHT as a decide watch over arm.”

As for the chance of using cabozantinib alone in the decide watch over arm, Agarwal eminent that it did no longer a good deal improve OS in the segment III COMET-1 trial, and that may possibly enjoy made it disturbing as a decide watch over arm when making an are trying to convince institutional overview boards.

See Particulars

CONTACT-02 randomized 507 mCRPC patients 1:1 to gather both oral cabozantinib once every day plus IV atezolizumab every 3 weeks or second-line NHT with both oral abiraterone plus prednisone or oral enzalutamide once a day.

Median age changed into 71 years and patients had a median baseline prostate-explicit antigen (PSA) stage of 25-34 ng/mL. About 80% of patients had bone metastases and about 75% had enlarged lymph nodes.

Agarwal eminent that the mix changed into particularly efficient in two prespecified subgroups of particular hobby, patients with liver metastases and these with prior docetaxel:

• Liver metastases: median rPFS of 6.2 vs 2.1 months (HR 0.43, 95% CI 0.27-0.68)
• Prior docetaxel: 8.8 vs 4.1 months (HR 0.57, 95% CI 0.34-0.97)

The target response charge changed into 14% with the mix versus 4% with second NHT, with 1% of patients in the mix arm attaining a total response.

As for security, grade 5 remedy-emergent unfavorable events (TEAEs) happened in 9% and 12% of the mix and NHT fingers, respectively, and no grade 5 TEAEs happened in both arm. TEAEs ended in the discontinuation of all remedy substances in 16% of the mix arm and 15% of NHT-switch arm.