New Approach For MCRPC | Dr. Catalona

Summary

The CONTACT-02 study found that a combination treatment of Cabozantinib and Atezolizumab (C+A) can significantly improve outcomes for patients with advanced prostate cancer that has spread to other parts of the body (metastatic castration-resistant prostate cancer or mCRPC) and has progressed after prior hormone therapy.

In this phase 3 study, patients receiving the C+A treatment had a longer time before their cancer progressed on scans (radiographic progression-free survival) compared to the control group receiving a second hormone therapy. The improvement was particularly notable in patients with liver metastases and those who had previously received chemotherapy.

The C+A group did experience more treatment-related side effects than the control group, with common side effects including hypertension, anemia, diarrhea, and fatigue. However, the side effects were manageable, and a similar percentage of patients in both groups discontinued treatment due to side effects.

This study is significant because it is the only phase 3 study of an immunotherapy-based treatment to show a meaningful improvement in progression-free survival for prostate cancer patients with metastases in organs other than the lymph nodes. The study is still ongoing to assess the impact on overall survival.

Clinical Impact

The results of the CONTACT-02 study could have a significant impact on clinical practice for several reasons:

1. New treatment option: The study introduces a new, potentially effective treatment combination (Cabozantinib plus Atezolizumab) for patients with advanced, metastatic castration-resistant prostate cancer (mCRPC) who have progressed on prior hormone therapy. This could provide clinicians with an additional treatment option for this patient population.
2. Improved outcomes: The study demonstrated a significant improvement in radiographic progression-free survival, particularly in patients with liver metastases and those who had previously received chemotherapy. These findings may guide clinicians in selecting the most appropriate treatment for their patients based on their specific disease characteristics.
3. Immunotherapy in prostate cancer: This study is the first phase 3 trial to show a meaningful improvement in progression-free survival using an immunotherapy-based treatment for prostate cancer patients with visceral metastases. This could lead to increased interest in and use of immunotherapy-based approaches in the treatment of advanced prostate cancer.
4. Manageable side effects: Although the Cabozantinib plus Atezolizumab group experienced more treatment-related side effects compared to the control group, these side effects were considered manageable. This information can help clinicians and patients weigh the potential benefits and risks of this treatment approach.
5. Potential change in treatment guidelines: If the overall survival data from this ongoing study demonstrate a significant improvement, the Cabozantinib plus Atezolizumab combination could potentially be included in future treatment guidelines for mCRPC, influencing the standard of care for this patient population.

However, it is essential to note that the study is still ongoing, and the overall survival data, which is a critical endpoint, is not yet mature. The impact on clinical practice will likely depend on the final results of the study, as well as further research to confirm these findings.

Questions

As a man with advanced metastatic castration-resistant prostate cancer (mCRPC), there are several important questions you should consider asking your oncologist about the CONTACT-02 study:

1. Am I eligible for the Cabozantinib plus Atezolizumab (C+A) treatment based on my current disease status and treatment history?
2. How does the C+A treatment compare to my current treatment options in terms of potential benefits and risks?
3. What are the most common side effects associated with the C+A treatment, and how can they be managed?
4. Given my specific disease characteristics (e.g., presence of liver metastases, prior chemotherapy), how might the C+A treatment potentially benefit me based on the study results?
5. Is the C+A treatment currently available, or is it still under investigation? If it's not yet available, are there any clinical trials offering this treatment that I might be eligible for?
6. How does the improvement in radiographic progression-free survival seen in the study translate to potential improvements in overall survival or quality of life?
7. Will my insurance cover the C+A treatment, or are there any financial assistance programs available if needed?
8. How does this study compare to other ongoing or recently completed studies investigating new treatments for advanced mCRPC?
9. Based on my current health status and treatment goals, do you recommend considering the C+A treatment approach?
10. How will you monitor my response to the treatment and make adjustments if needed?

Remember, every patient's situation is unique, and your oncologist can provide personalized guidance based on your specific medical history, current health status, and treatment goals. Don't hesitate to ask any additional questions or express any concerns you may have about this study or your treatment plan in general.

Categories: Spring 2024

New study results found that Cabozantinib plus Atezolizumab (C+A) can significantly improve prognoses of patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed with prior novel hormonal therapy.

This phase 3 study, found that patients in the C+A group had longer radiographic progression-free survival (6.3 months) compared with the control group, though the group did experience more treatment-adverse events than the C+A group resulting in 16% of the control group discontinuing treatment versus 15 percent of the control group. The most common adverse effects include hypertension, anemia, diarrhea, and fatigue.

18 Oral Abstract Session

CONTACT-02: 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).

Neeraj Agarwal, Arun Azad, Joan Carles, Nobuaki Matsubara, Stephane Oudard, Fred Saad, Axel S. Merseburger, Andrey Soares, Bradley Alexander McGregor, Bogdan Zurawski, Scott A. North, Marinos Tsiatas, Igor Bondarenko, Margarita Sonia Alfie, Lena Evilevitch, Keerti Sharma, Prachi Nandoskar, Roberta Ferraldeschi, Fong Wang, Sumanta Kumar Pal; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Peter MacCallum Cancer Centre; and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; Department of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan; Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP.Centre – UniversitéParis Cit´e, Paris, France; Centre Hospitalier de l’Universit´e de Montr´eal, Montreal, QC, Canada; Department of Urology, Campus L¨ubeck, University Hospital Schleswig-Holstein, L¨ubeck, Germany; Centro Paulista de Oncologia, Hospital Israelita Albert Einstein and Latin American Cooperative Oncology Group (LACOG), S~ao Paulo, Brazil; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland; Division of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; Athens Medical Center, Kifissia-Athens, Greece; Department of Oncology and Medical Radiology, Dnipropetrovsk Medical Academy, Dnipro, Ukraine; Clinic Hospital, Buenos Aires, Argentina; Exelixis, Inc., Alameda, CA; Roche, Inc., Basel, Switzerland; Department of Medical Oncology & Therapeutics, City of Hope Comprehensive Cancer Center, Duarte, CA

Abstract

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 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 PFS 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 PFS 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 PFS 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 PFS in prostate cancer with visceral metastasis.

Follow-up for OS is ongoing.

Clinical trial information: NCT04446117.

Research Sponsor: Exelixis, Inc.

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