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PEER-TO-PEER CLINICAL CONVERSATIONS |
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CONTACT-02 Trial Results: Cabozantinib Plus Atezolizumab for mCRPC
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Neeraj Agarwal, MD, FASCO
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| Oliver Sartor interviews Neeraj Agarwal about the CONTACT-02 trial, which compares cabozantinib plus atezolizumab to second ARPI in metastatic castrate-resistant prostate cancer patients. Dr. Agarwal presents the final overall survival results from the study, which show improved progression-free survival with the combination therapy, particularly in patients with liver or bone metastasis.
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Olaparib plus Abiraterone Versus Placebo plus Abiraterone in Metastatic Castration-Resistant Prostate Cancer (PROpel): Final Prespecified Overall Survival Results of a Randomised, Double-Blind, Phase 3 Trial
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Fred Saad, MD, FRCS
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| PROpel met its primary endpoint showing statistically significant improvement in radiographic progression-free survival with olaparib plus abiraterone versus placebo plus abiraterone in patients with first-line metastatic castration-resistant prostate cancer (mCRPC) unselected by homologous recombination repair mutation (HRRm) status.
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| NePtune Trial: Evaluating Neoadjuvant PARP Inhibition in BRCA-Mutated Prostate Cancer |
| Rana McKay, MD |
| Rana McKay discusses the NePtune study, investigating PARP inhibitors as a neoadjuvant treatment for prostate cancer patients with BRCA1/2 mutations. This study, inspired by the success of PARP inhibitors in metastatic settings and neoadjuvant successes in other cancers, aims to address the aggressive nature of BRCA-mutated prostate cancer earlier in the disease course. |
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CONTACT-02 – Signs of Activity with Cabozantinib for
Prostate Cancer, Yet There Is Still More to Be Desired
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Evan Yu, MD
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| Cabozantinib, a MET and VEGFR2 tyrosine kinase inhibitor, has shown mixed results in metastatic castration-resistant prostate cancer (mCRPC). The CONTACT-02 trial demonstrated improved progression-free survival (PFS) with cabozantinib plus atezolizumab over a second ARPI but no overall survival benefit except in subgroups with liver or bone metastases. While promising for specific populations, the findings raise questions about the control arm's adequacy and cabozantinib's role in clinical practice, particularly versus chemotherapy for high-risk patients.
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| Cabozantinib plus Atezolizumab versus 2nd Novel Hormonal Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer: Final Overall Survival Results of the Phase III, Randomized, CONTACT-02 Study |
| Neeraj Agarwal, MD |
| The CONTACT-02 trial evaluated cabozantinib plus atezolizumab versus a second novel hormonal therapy in metastatic castration-resistant prostate cancer (mCRPC) patients post-NHT. The combination improved progression-free survival significantly, with notable benefits in liver metastases. However, overall survival improvement was not statistically significant. |
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| CONTACT-02 Study and STAMPEDE Docetaxel Trials |
| Rana McKay, MD |
| The CONTACT-02 trial demonstrated improved progression-free survival with cabozantinib + atezolizumab in mCRPC patients, particularly those with liver metastases, but failed to show an overall survival benefit and had significant toxicity. Meanwhile, a post-hoc STAMPEDE analysis highlighted the Decipher biomarker's ability to predict survival benefit with docetaxel + ADT, offering a tool for tailoring therapy, especially for low-volume mHSPC. Both studies emphasize the need for personalized approaches in high-risk prostate cancer populations. |
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| ADT Sparing Approaches in the Metastatic Hormone-Sensitive and Castrate-Resistant Spaces |
| Karen A. Autio, MD, MSc |
| Karen Autio reviews ADT-sparing strategies in prostate cancer to reduce the toxicities associated with long-term androgen deprivation therapy (ADT). For oligorecurrent disease, stereotactic ablative radiotherapy (SABR) was highlighted for delaying progression and prolonging ADT-free survival based on trials like SABR-COMET, ORIOLE, and STOMP. While these approaches show promise, ADT remains essential in metastatic castration-resistant prostate cancer (mCRPC), though emerging treatments like bipolar androgen therapy (BAT) may offer future alternatives. |
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| Combination of PARP Inhibitors and Androgen Receptor Pathway Inhibitors in Metastatic Castration-Resistant Prostate Cancer - Beyond the Abstract
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| Arun A. Azad, MBBS, PhD, FRACP, and Louise Kostos, PhD candidate
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| The combination of PARP inhibitors and androgen receptor pathway inhibitors represents a promising therapeutic strategy in mCRPC, particularly in patients with homologous recombination repair mutations. Phase III trials—PROpel, MAGNITUDE, and TALAPRO-2—showed the greatest benefit in BRCA-mutated mCRPC, with HRR-mutated patients also deriving significant but lesser advantages. However, patients without HRR mutations experienced limited benefit, highlighting the importance of early HRR testing to guide treatment decisions.
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| Biomarkers Associated with Outcomes from KEYLYNK-010: Pembrolizumab plus Olaparib Versus Next-Generation Hormonal Agent in Previously Treated Metastatic Castration-Resistant Prostate Cancer |
| Evan Y. Yu, MD |
| The KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus next-generation hormonal agents (NHA) in previously treated mCRPC patients, identifying key biomarkers linked to treatment outcomes. Pembrolizumab + olaparib showed improved rPFS in patients with HRRm, BRCAm, and PD-L1 CPS ≥1, with a potential OS and rPFS benefit observed in AR-V7+ patients, though further validation is needed. No biomarkers predicted outcomes for NHA, highlighting the need for improved biomarker-driven strategies in mCRPC. |
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