Rucaparib or Physician’s Choice in Metastatic Prostate Cancer

Fizazi, Karim; Piulats, Josep María; Reaume, M. Neil; Ostler, Peter; McDermott, Ray; Gingerich, Joel Roger; Pintus, Elias; Sridhar, Srikala S.; Bambury, Richard; Emmenegger, Urban; Lindberg, Henriette; Morris, David; Nolè, Franco; Staffurth, John; Redfern, Charles H.; Sáez, María Isabel Corbí; Abida, Wassim; Daugaard, Gedske; Heidenreich, Axel; Krieger, Laurence E.; Sautois, Brieuc; Loehr, Andrea; Despain, Darrin; Heyes, C.; Watkins, Simon P.; Chowdhury, Simon; Ryan, Charles J.; Bryce, Alan H.

doi:10.1056/nejmoa2214676

Cited by 169 publications

(122 citation statements)

References 26 publications

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“…Results of the TRITON2 study led to accelerated FDA approval of rucaparib for patients with mCRPC and a germline or somatic BRCA1/2 alteration who have progressed on ARSI and a taxane-based chemotherapy. This approval was conditional based on the results from the TRITON3 trial, which is a phase III trial of rucaparib vs chemotherapy or second line androgen deprivation therapy in patients with mCRPC with mutations in BRCA or ATM who had disease progression following treatment with an ARSI ( 39 ). This study randomized patients in a 2:1 ratio to receive oral rucaparib 600mg BID or physician’s choice control (docetaxel or ARSI).…”

Section: Parpi Monotherapymentioning

confidence: 99%

PARP inhibitors in metastatic prostate cancer

et al. 2023

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Poly-ADP ribose polymerase inhibitors (PARPi) are an emerging therapeutic option for the treatment of prostate cancer. Their primary mechanism of action is via induction of synthetic lethality in cells with underlying deficiencies in homologous recombination repair (HRR). In men with metastatic castrate-resistant prostate cancer (mCRPC) and select HRR pathway alterations, PARPi treatment has been shown to induce objective tumor responses as well as improve progression free and overall survival. Presently, there are two PARPi, olaparib and rucaparib, that are FDA approved in the treatment of mCRPC. Ongoing research is focused on identifying which HRR alterations are best suited to predict response to PARPi so that these therapies can be most effectively utilized in the clinic. While resistance to PARPi remains a concern, combination therapies may represent a mechanism to overcome or delay resistance.

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Section: Parpi Monotherapymentioning

confidence: 99%

PARP inhibitors in metastatic prostate cancer

et al. 2023

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“…For example, in BRCA - altered patients who had disease progression after treatment with an API for CRPC or hormone-sensitive disease, the PARP inhibitor rucaparib resulted in improved imaging-based progression-free survival compared with the use of docetaxel or an alternative API (median, 11.2 months v 6.4 months; HR, 0.50 [95% CI, 0.36 to 0.69]). 6 Hence, one disadvantage of upfront treatment intensification with docetaxel-containing triplet therapies is that it might hamper the implementation of novel sequencing strategies. The opinion of the authors on these points would be appreciated.…”

Section: To the Editormentioning

confidence: 99%

“…Through indirect comparisons, a recent network meta-analysis concluded that, as compared with a doublet therapy of ADT 1 an API, the benefit with docetaxelcontaining triplet regimens as regards OS was uncertain, whereas adverse events were increased. 4 Novel therapies, such as radioligand therapy targeting prostate-specific membrane antigen (PSMA) with 177 Lu-PSMA-617 and poly (ADP-ribose) polymerase (PARP) inhibitors, 5,6 which offered excellent results with low toxicity in heavily pretreated patients, are now being actively investigated in the earlier setting, including in taxane-na ïve patients. For example, in BRCA-altered patients who had disease progression after treatment with an API for CRPC or hormone-sensitive disease, the PARP inhibitor rucaparib resulted in improved imaging-based progression-free survival compared with the use of docetaxel or an alternative API (median, 11.2 months v 6.4 months; HR, 0.50 [95% CI, 0.36 to 0.69]).…”

mentioning

confidence: 99%

Triplet Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer

Hindié

2023

JCO

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“…These data have recently been published. 55 Zachary Morris (University of Wisconsin) discussed studies on the potential for combining a novel tumor membrane-targeted radiotherapy with immunotherapy. Alkylphosphocholines are phospholipids that are abundant in most tumor cell membranes, present at a level 6-10 times higher than normal cells.…”

Section: Targeting a Tumor-specific Cd46 Epitope In Mcrpcmentioning

confidence: 99%

The 29th Annual Prostate Cancer Foundation Scientific Retreat Report

Miyahira,

Soule

2023

The Prostate

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BackgroundThe 29th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 27 to 29, 2022, at the Omni La Costa Resort in Carlsbad, CA. This was the first‐ever hybrid PCF Retreat.MethodsThe Annual PCF Scientific Retreat is a prominent international scientific gathering centered on groundbreaking, unpublished, and influential studies in basic, translational, and clinical prostate cancer research. It also covers research from related fields with a strong potential for influencing prostate cancer research and patient care.ResultsKey areas of research that were focused on at the 2022 PCF Retreat included: (i) the contributions of molecular and genomic factors to prostate cancer disparities; (ii) novel clinical trial updates; (iii) lessons from primary prostate cancer; (iv) lessons from single‐cell studies; (v) genetic, epigenetic, epitranscriptomic and posttranslational mechanisms and clinical heterogeneity in prostate cancer; (vi) biology of neuroendocrine and lineage‐plastic prostate cancer; (vii) next generation prostate cancer theranostics and combination therapies; (viii) the biology and therapeutic potential of targeting phosphoinositide 3‐kinases pathways; (ix) combining immunomodulatory treatments for prostate cancer; (x) novel gamma delta (γδ) T‐cell therapy platforms for oncology; and (xi) lessons from other cancers.ConclusionsThis article provides a summary of the presentations from the 2022 PCF Scientific Retreat. By disseminating this knowledge, we hope to enhance our understanding of the present research landscape and guide future strides in both prostate cancer research and patient care.

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Rucaparib or Physician’s Choice in Metastatic Prostate Cancer

Cited by 169 publications

References 26 publications

PARP inhibitors in metastatic prostate cancer

PARP inhibitors in metastatic prostate cancer

Triplet Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer

The 29th Annual Prostate Cancer Foundation Scientific Retreat Report

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