Most Read Articles
Dr Margaret Shi, 18 May 2020

A blood test is shown to be feasible and safe for early detection of multiple cancers in women with no current or known history of cancer, enabling early treatment with curative intent in a subset of individuals.

Christina Lau, 20 Apr 2020

Hippocampal avoidance during whole-brain radiotherapy (HA-WBRT), together with memantine, better preserves cognitive function vs WBRT plus memantine in patients with brain metastases, without compromising survival, a multi-institutional phase III trial has shown.

Natalia Reoutova, 20 May 2020

Cancer patients infected with coronavirus disease 2019 (COVID-19) appear to be at higher risk of severe outcomes, including death, but cancer type and treatment serve as better predictors, according to recent research presented at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting I.

At the time of writing, COVID-19 has spread to more than 200 countries and territories, affecting an estimated 4.5 million people and killing over 300,000. Cancer, on the other hand, is newly diagnosed in 18 million people and takes the lives of 10 million every year.

“We have invited physician scientists who are at the epicentre of the COVID-19 pandemic, taking care of patients with cancer. They gathered prospective information to understand the effects of COVID-19 on patients with cancer, are testing new treatments, and are making this knowledge available to the global research community, so we can all benefit from their experience,” said Professor Antoni Ribas from UCLA Medical Center, Los Angeles, California, US, chairperson of the COVID-19 and cancer plenary session of the meeting.

Natalia Reoutova, 28 May 2020

Fasting-mimicking diet (FMD) cycles in combination with endocrine therapy (ET) cause metabolic changes in hormone receptor (HR)-positive breast cancer patients analogous to those observed in animal models, where they are associated with anticancer activity.

PARP inhibitor therapy changes paradigm of mCRPC management

Dr Margaret Shi
27 Feb 2020

Olaparib, a poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor, represents a paradigm shift in management of metastatic castration-resistant prostate cancer (mCRPC) in view of the promising results shown in recent trials, said Professor Przemyslaw Twardowski of John Wayne Cancer Institute of Santa Monica, California, US, who spoke at the Uro-Oncology Asia 2020 conference.

Olaparib demonstrated tumour response in patients with germline BRCA mutated advanced prostate cancer in Study 42, as well as significant improvements in objective response rate (ORR), radiologic progression-free survival (rPFS) and overall survival (OS) in biomarker-positive patients (n=16) compared with biomarker-negative patients (n=33) (ORR, 87.5 percent vs 6.1 percent, p<0.001; rPFS, 9.8 months vs 2.7 months; p<0.001) (mOS, 13.8 months vs 7.5 months; p=0.05) in the TOPARP-A trial. The positive findings of olaparib in biomarker-selected mCRPC were confirmed in the TOPARP-B trial. [N Engl J Med 2015;373:1697-1708; Mateo J, et al, ASCO 2019, abstract 5005]

“PROfound is the first positive biomarker-selected phase III study evaluating a PARP inhibitor in patients with mCRPC. Results highlight the importance of genomic testing in this population,” said Twardowski.

The benefits of olaparib demonstrated in the PROfound study has led to a priority review granted by the US FDA in January 2020 for its use in patients with homologous recombination repair (HRR)-mutated mCRPC.

In the PROfound trial, mCRPC patients (median age, ≥67 years) with disease progression on prior new hormonal agent (eg, abiraterone acetate and/or enzalutamide) treatment who had HRR mutation in one of 15 genes (BRCA1/2 or ATM genes [cohort A, n=245] or other HRR mutations [cohort B, n=142]) confirmed by prospective tissue analysis were randomized (2:1) to receive olaparib tablets (300 mg BID) or physician’s choice of either enzalutamide (160 mg orally QD) or abiraterone acetate (1,000 mg orally QD, plus 5 mg prednisolone BID). [de Bono JS, et al, ASCO 2017, abstract TPS5091]

A significant improvement in rPFS was demonstrated with olaparib in cohort A (median, 7.39 months vs 3.55 months; hazard ratio [HR], 0.34; 95 percent confidence interval [Cl], 0.25 to 0.47; p<0.0001) compared with physician’s choice of enzalutamide or abiraterone. Consistent rPFS benefits of olaparib were shown across all predefined subgroups in cohort A. [Hussain M, et al, ESMO 2019, abstract LBA12_PR]

Similarly, rPFS was improved with olaparib (mPFS, 5.82 months vs 3.52 months; HR, 0.49; 95 percent CI, 0.38 to 0.63) vs physician’s choice of enzalutamide or abiraterone the overall population of patients with any of the qualifying HRR mutations.

Olaparib also demonstrated, in cohort A, a 21-fold increase in ORR (33.3 percent vs 2.3 percent; odds ratio, 20.86; 95 percent CI, 4.18 to 379.18; p<0.0001) as well as a statistically significant and clinically meaningful delay in time to pain progression (TTPP) assessed by Brief Inventory-Short Form (median TTPP, not reached vs 9.92 months; HR, 0.44; 95 percent CI, 0.22 to 0.91; p=0.0192) compared with physician’s choice of enzalutamide or abiraterone.

The adverse event (AE) profile of olaparib in PROfound was consistent with its known safety profile, with anaemia and nausea being the most common AEs.

“Clinical activity of olaparib was also shown in patients with alternations in non-BRCA HRR genes. These also predict responsiveness to immunotherapy,” said Twardoswki. “However, gene-level analysis is complex and exploratory, and detailed analysis of gene-level effects on multiple endpoints is ongoing.”

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Most Read Articles
Dr Margaret Shi, 18 May 2020

A blood test is shown to be feasible and safe for early detection of multiple cancers in women with no current or known history of cancer, enabling early treatment with curative intent in a subset of individuals.

Christina Lau, 20 Apr 2020

Hippocampal avoidance during whole-brain radiotherapy (HA-WBRT), together with memantine, better preserves cognitive function vs WBRT plus memantine in patients with brain metastases, without compromising survival, a multi-institutional phase III trial has shown.

Natalia Reoutova, 20 May 2020

Cancer patients infected with coronavirus disease 2019 (COVID-19) appear to be at higher risk of severe outcomes, including death, but cancer type and treatment serve as better predictors, according to recent research presented at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting I.

At the time of writing, COVID-19 has spread to more than 200 countries and territories, affecting an estimated 4.5 million people and killing over 300,000. Cancer, on the other hand, is newly diagnosed in 18 million people and takes the lives of 10 million every year.

“We have invited physician scientists who are at the epicentre of the COVID-19 pandemic, taking care of patients with cancer. They gathered prospective information to understand the effects of COVID-19 on patients with cancer, are testing new treatments, and are making this knowledge available to the global research community, so we can all benefit from their experience,” said Professor Antoni Ribas from UCLA Medical Center, Los Angeles, California, US, chairperson of the COVID-19 and cancer plenary session of the meeting.

Natalia Reoutova, 28 May 2020

Fasting-mimicking diet (FMD) cycles in combination with endocrine therapy (ET) cause metabolic changes in hormone receptor (HR)-positive breast cancer patients analogous to those observed in animal models, where they are associated with anticancer activity.