CONTACT-2: Phase 3 study of cabozantinib (C) plus atezolizumab (A) vs second novel hormonal therapy (NHT) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Author(s): Neeraj Agarwal¹; Arun Azad²; Joan Carles³; Nobuaki Matsubara⁴; Stephane Oudard⁵; Fred Saad⁶; Axel S. Merseburger⁷; Andrey Soares⁸; Bradley Alexander McGregor⁹; Bogdan Zurawski¹⁰; Scott A. North¹¹; Marinos Tsiatas¹²; Igor Bondarenko¹³; Margarita Sonia Alfie¹⁴; Lena Evilevitch¹⁵; Keerti Sharma¹⁵; Prachi Nandoskar¹⁵; Roberta Ferraldeschi¹⁶; Fong Wang¹⁵; Sumanta Kumar Pal¹⁷

Source: https://doi.org/10.1200/JCO.2024.42.4_suppl.18

Dr. Maen Hussein's Thoughts

The role for immunotherapy in combination with multitargeted therapy in prostate cancer, for patients who had previous docetaxol, or had visceral disease (liver) showed more benefit from the combination vs. second novel hormonal therapy. Recall that patients who had exposure to docetaxol can be treated with pluvicto. Genomic and genetic testing is encouraged for those patients as PARP targeted mutations can be found (homologous recombination-repair mutations).

BACKGROUND

Pts who have progressed on a prior NHT and have mCRPC with extrapelvic nodal or visceral metastasis have a poor prognosis with limited, broadly available treatment options beyond chemotherapy. C promotes an immune-permissive tumor environment and may enhance response to immune checkpoint inhibitors (ICIs).

METHODS

Pts randomized 1:1 to C+A (C [40 mg PO QD] + A [1200 mg IV Q3W]) or control (ctrl) (abiraterone [1000 mg PO QD] + prednisone [5 mg PO BID] or enzalutamide [160 mg PO QD]) were stratified by liver metastasis (yes/no), prior docetaxel for mCSPC (yes/no), and prior NHT for mCSPC/M0CRPC/mCRPC. Key eligibility criteria: mCRPC with disease progression on one prior NHT, measurable extrapelvic nodal or visceral disease, ECOG PS ≤1, ongoing androgen deprivation therapy. Docetaxel was allowed for mCSPC. Dual primary endpoints are radiographic PFS (rPFS) by blinded independent radiology committee (BIRC) per RECIST 1.1 in the first 400 randomized pts (PITT) and OS in all randomized pts (ITT). Secondary endpoint is ORR by RECIST 1.1 per BIRC.

RESULTS

At the data cutoff (Feb 28, 2023), 507 pts (ITT) were randomized to receive C+A (n=253) or ctrl (n=254). Baseline and clinical characteristics were balanced between C+A and ctrl arms: 25% and 26% had liver metastasis, 21% and 20% received docetaxel for mCSPC, and 72% and 74% received first NHT for mCRPC. Median follow-up was 12.0 mo for ITT and 14.3 mo for PITT populations. Median rPFS was significantly longer with C+A vs ctrl (6.3 vs 4.2 mo; HR 0.65, 95% CI 0.50-0.84; P=0.0007) including in subgroups with liver metastasis (6.0 vs 2.1 mo; HR 0.47 [95% CI 0.30- 0.74]) or prior docetaxel treatment for mCSPC (8.8 vs 4.1 mo; HR 0.55 [0.32-0.96]). ORR was higher in C+A vs ctrl in pts with follow-up ≥6 mo in ITT (13.6% [23/169] vs 4.2% [7/165]). Median DOR was 9.7 mo for C+A vs not reached for ctrl, and time to response was 2.3 vs 4.6 mo. DCR was 72.8% (123/169) vs 54.5% (90/165). OS data are immature. Treatment-emergent adverse events (TEAE) occurred in 97% in C+A vs 87% in ctrl (grade 3/4 events, 48% vs 23%). Grade 5 TEAEs occurred in 9% vs 12% and no grade 5 treatment-related AEs occurred in either arm. TEAEs led to the discontinuation of all treatment components in 16% in C+A and 15% in ctrl.

CONCLUSIONS

C+A significantly improved rPFS vs second NHT in pts who had progressed on a prior NHT and have mCRPC with extrapelvic nodal or visceral disease, a population with high unmet medical need. These rPFS benefits were particularly notable in pts with liver metastasis and those who previously received docetaxel for mCSPC. Toxicities reported with each treatment arm were manageable. CONTACT-02 is the only phase 3 study of an ICI-based regimen to show a significant and clinically meaningful improvement in rPFS in prostate cancer with visceral metastasis. Follow-up for OS is ongoing.

Author Affiliations

¹Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; ²Peter MacCallum Cancer Centre; and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; ³Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; ⁴Department of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan; ⁵Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP.Centre – Université Paris Cité, Paris, France; ⁶Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada; ⁷Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany; ⁸Centro Paulista de Oncologia, Hospital Israelita Albert Einstein and Latin American Cooperative Oncology Group (LACOG), São Paulo, Brazil; ⁹Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; ¹⁰Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland; ¹¹Division of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; ¹²Athens Medical Center, Kifissia-Athens, Greece; ¹³Department of Oncology and Medical Radiology, Dnipropetrovsk Medical Academy, Dnipro, Ukraine; ¹⁴Clinic Hospital, Buenos Aires, Argentina; ¹⁵Exelixis, Inc., Alameda, CA; ¹⁶Roche, Inc., Basel, Switzerland; ¹⁷Department of Medical Oncology & Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA

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