AZ, MSD’s Lynparza/Abiraterone Combo Hits Prostate Cancer Goals

Excerpt:

“AstraZeneca and MSD have presented data at ASCO showing improvement in radiologic progression-free survival (rPFS) in prostate cancer patients taking a combination of Lynparza and abiraterone.

“Study 08 – a randomised, double-blinded, multi-centre Phase II trial – compared Lynparza (olaparib) in combination with abiraterone to abiraterone alone in patients with previously-treated metastatic castration-resistant prostate cancer, (mCRPC), regardless of homologous recombination repair (HRR) mutation status.”

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AR-V7+ CTCs Predicted Worse PFS, OS in mCRPC

Excerpt:

“Detection of circulating tumor cells (CTCs) positive for the nuclear-specific AR-V7 protein was an independent predictor of shortened progression-free survival (PFS) and overall survival (OS) when treating metastatic castration-resistant prostate cancer (mCRPC) with abiraterone or enzalutamide, according to results of the PROPHECY study (abstract 5004). The findings were presented at the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO), held June 1–5 in Chicago.

“’Men with AR-V7–positive CTCs have a very low probability of benefit from abiraterone or enzalutamide, ranging from 0% to 11%,’ said Andrew J. Armstrong, MD, of Duke Cancer Institute. ‘However, a lack of AR-V7 detection does not guarantee response or benefit’ where these therapies are concerned, he added.”

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Abiraterone May Be More Effective in Black Men With Prostate Cancer

Excerpt:

“Black men with metastatic castration-resistant prostate cancer (CRPC) who received hormonal therapy with the adrenal inhibitor abiraterone had greater and longer-lasting responses compared with white men, according to the results of a late-breaking study (abstract LBA5009) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held in Chicago June 1–5.

“The prospective study found that black men were more likely to have a decline in prostate-specific antigen (PSA) and had a longer median time to PSA worsening than white men. The findings were presented by Daniel George, MD, professor of medicine and surgery at Duke University.”

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Low-Dose Abiraterone With Food vs Standard-Dose Abiraterone in Castration-Resistant Prostate Cancer

Excerpt:

“In a phase II trial reported in the Journal of Clinical Oncology, Szmulewitz et al found that low-dose abiraterone (Zytiga) given with a low-fat meal was noninferior to standard-dose abiraterone in the fasting state with regard to reduction in prostate-specific antigen (PSA) levels among patients with castration-resistant prostate cancer.”

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Janssen’s Zytiga Approved for Earlier Use in Prostate Cancer

Excerpt:

“European regulators are allowing earlier use of Janssen’s Zytiga in the treatment pathway for metastatic prostate cancer.

“Zytiga (abiraterone) plus prednisone/prednisolone has been approved to treat newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) in adult men in combination with androgen deprivation therapy (ADT).

“The drug is already available in Europe for metastatic castration-resistant prostate cancer (mCRPC) in adults who are asymptomatic or mildly symptomatic after failure of ADT in whom chemotherapy is not yet clinically indicated and in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.”

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Benefits Vary With Docetaxel and Abiraterone in High-Risk Prostate Cancer

Excerpt:

“The first head-to-head comparison of docetaxel and abiraterone acetate for high-risk prostate cancer patients starting long-term hormone therapy found benefit with both treatments when added to androgen deprivation therapy (ADT). Treatment decisions may come down to specific toxicities, which differ between the treatments.

“The large STAMPEDE trial previously found that both docetaxel and abiraterone improved outcomes when compared with placebo. “Right now, oncologists and urologists want to know which combination is preferable, which is why we conducted this analysis,” said study author Matthew Sydes, MSc, a statistician at University College London.”

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Abiraterone/ADT Combo Increased Prostate Cancer Survival

Excerpt:

“Combined therapy with abiraterone acetate/prednisone plus androgen deprivation therapy (ADT) significantly improved overall survival and radiographic progression-free survival (PFS) among men with metastatic hormone-naive prostate cancer compared with ADT and placebo alone, according to the results of the phase III LATITUDE trial (abstract LBA3) presented at the 2017 ASCO Annual Meeting.

” ‘In my opinion, these findings support the fact that adding abiraterone and prednisone to castration should now be considered the new standard of care for men with newly diagnosed metastatic prostate cancer,’ said researcher Karim Fizazi, MD, PhD, head of the department of cancer medicine at Gustave Roussy, University Paris-Sud, Villejuif, France.”

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Cabazitaxel/Abiraterone Combination Promising in mCRPC

Excerpt:

“The combination of cabazitaxel and abiraterone was well tolerated and showed antitumor activity in previously treated patients with metastatic castration-resistant prostate cancer (mCRPC), according to a new phase I/II study.

” ‘Therapeutic options for men with mCRPC have evolved considerably with the approval of five therapies associated with improved overall survival,’ wrote study authors led by Christophe Massard, MD, PhD, of Gustave Roussy Cancer Campus in Villejuif, France. Still, ‘there is a need to provide robust evidence on how these agents should be used, in sequence or in combination, to achieve optimal medical management.’ ”

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ASCO: Combo Tx Fails in Local High-Risk Prostate Ca

Excerpt:

“Neoadjuvant enzalutamide (ENZA) and abiraterone acetate (AA) plus 5 mg prednisone daily can be given safely for 6 months in men with localized high-risk prostate cancer prior to prostatectomy, a neoadjuvant study showed.

“However, the findings did not favor adding ENZA to augment AA plus leuprolide acetate (LHRHa) efficacy in localized high-risk prostate cancer, Eleni Efstathiou, MD, PhD, of the University of Texas MD Anderson Cancer Center, in Houston, said during a presentation at the American Society of Clinical Oncology.

“Pathologic downstaging (≤ pT2N0) occurred in 30% of patients treated with the combination therapy (AA+ENZA+ LHRHa) versus 52% of patients who received AA plus LHRHa alone (P=0.07), the study showed. Despite universal PSA depletion (≤ 0.1), a wide range of viable tumor was observed (volume 0-8.64 cc, cellularity 0-90%, and a tumor epithelial volume [TEV] 0-5.58 cc). TEV and stage were aligned.”

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