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29 Nov 2019
Metformin Extended Release 500 mg,750 mg, and 1000 mg
30 Nov 2018
New drug applications approved by US FDA as of 16 - 30 November 2018 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.
Roshini Claire Anthony, 16 Dec 2016

Five years of extended therapy with the aromatase inhibitor (AI) letrozole did not improve survival in postmenopausal breast cancer patients, according to findings of the NRG Oncology/NSABP B-42 trial presented at the San Antonio Breast Cancer Symposium (SABCS 2016) held in Texas, US. 

Jackey Suen, 21 Dec 2016

Adding everolimus to fulvestrant in second-line treatment of hormone receptor (HR)-positive, HER2-negative advanced breast cancer improves progression-free survival (PFS) by 40 percent, the phase II PrECOG 0102 study has shown. [SABCS 2016, abstract S1-02]

First-line olaparib maintenance improves PFS in advanced ovarian cancer

Roshini Claire Anthony
10 Oct 2019
Professor Isabelle Ray-Coquard

A maintenance regimen comprising olaparib and bevacizumab led to greater progression-free survival (PFS) in patients newly diagnosed with advanced ovarian cancer, results of the phase III PAOLA-1/ENGOT-ov25* study showed.

“PAOLA-1/ENGOT-ov25 [demonstrated] a statistically significant improvement in PFS in the ITT** population when olaparib was added to bevacizumab as a standard of care,” said study author Professor Isabelle Ray-Coquard from the Centre Leon Berard and University Claude Bernard Lyon, Lyon, France, at ESMO 2019.

Participants were 806 women newly diagnosed with FIGO*** stage III–IV high-grade serous or endometrioid ovarian, fallopian tube, or primary peritoneal cancer, who had received surgery, platinum-taxane chemotherapy, and 3 cycles of bevacizumab (15 mg/kg Q3W for 15 months). They were randomized 2:1 to receive the PARP inhibitor olaparib (300 mg BID for 2 years) plus bevacizumab (15 mg/kg Q3W for 15 months; median age 61 years) or bevacizumab alone (median age 60 years).

Investigator-assessed PFS was significantly improved with the addition of olaparib to bevacizumab compared with bevacizumab alone (median 22.1 vs 16.6 months; hazard ratio [HR], 0.59, 95 percent confidence interval [CI], 0.49–0.72; p<0.0001). [ESMO 2019, abstract LBA2]

The PFS benefit was observed in all clinical subgroups assessed, said Ray-Coquard. The results were also consistent when assessed by BICR# (median 26.1 vs 18.3 months; HR, 0.63, 95 percent CI, 0.51–0.77; p<0.0001).

Olaparib was associated with a significant improvement in the time to first subsequent therapy or death (median 24.8 vs 18.5 months; HR, 0.59; p<0.0001), and a trend toward an improvement in time to second progression or death (median 32.3 vs 30.1 months; HR, 0.86), though the findings for the latter are immature. 

The magnitude of PFS benefit with olaparib appeared greater among patients with tBRCA mutations (median 37.2 vs 21.7 months with bevacizumab alone; HR, 0.31) than those without (median 18.9 vs 16.0 months; HR, 0.71) and among those who were HRD positive (score ≥42), be it those with or without tBRCA mutations (HR, 0.33 and HR, 0.43, respectively) vs HRD negative or with unknown HRD status (HR, 0.92).

“The results reveal a patient population beyond [those with tBRCA mutations], who are HRD positive, that experiences substantial benefit from maintenance treatment with olaparib and bevacizumab,” said Ray-Coquard.

Grade ≥3 treatment-related adverse event (AE) incidence was comparable between olaparib-bevacizumab and bevacizumab-alone recipients (57 percent vs 51 percent), as was serious AEs (31 percent each). However, AE-related dose interruptions, reductions, and discontinuations were more common among olaparib-bevacizumab recipients (54 percent vs 24 percent, 41 percent vs 7 percent, and 20 percent vs 6 percent, respectively). The most common grade ≥3 AE was hypertension (19 and 30 percent of olaparib-bevacizumab and bevacizumab-alone recipients, respectively). There was one death in the olaparib-bevacizumab arm and four in the bevacizumab-alone arm.

Haematologic AEs namely MDS/AML/AA## occurred in six olaparib-bevacizumab recipients and in one bevacizumab-alone recipient, while seven and three patients, respectively, developed new primary malignancies. Six olaparib-bevacizumab recipients developed pneumonitis/interstitial lung disease. Health-related quality of life was comparable between groups (p=0.123).

“The safety profile of olaparib [plus] bevacizumab was generally consistent with previous trials of each drug and adding olaparib to bevacizumab did not impact bevacizumab tolerability,” said Ray-Coquard.

These results are practice-changing. Patients with high-grade serous or endometrioid ovarian cancer need to receive the most efficient combination we have now which is chemotherapy plus bevacizumab followed by bevacizumab plus olaparib, she noted.

However, without an olaparib monotherapy arm as a comparator, it is difficult to establish if the PFS benefit observed is due to olaparib or the synergistic combination of olaparib and bevacizumab, pointed out discussant Dr Ana Oaknin from the Vall d’Hebron Institute of Oncology, Barcelona, Spain.

 

Moving PARP inhibitors into the first-line setting

“PARP inhibitors have revolutionized the treatment landscape of ovarian cancer,” said discussant Dr Susana Banerjee from The Royal Marsden NHS Foundation Trust, London, UK. “But if we’re really going to have a chance to increase overall survival and hopefully more women cured, we need to bring these treatments into the first-line setting.”

Key questions that need answering include how to improve results from the standard of care, the possibility of more women benefitting from a first-line PARP inhibitor beyond those with BRCA mutations, how to select patients who would incur the greatest long-term benefits, the impact in women without HRD deficiency, and whether combining treatments improves outcomes, she said.

 

 

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Most Read Articles
29 Nov 2019
Metformin Extended Release 500 mg,750 mg, and 1000 mg
30 Nov 2018
New drug applications approved by US FDA as of 16 - 30 November 2018 which includes New Molecular Entities (NMEs) and new biologics. It does not include Tentative Approvals. Supplemental approvals may have occurred since the original approval date.
Roshini Claire Anthony, 16 Dec 2016

Five years of extended therapy with the aromatase inhibitor (AI) letrozole did not improve survival in postmenopausal breast cancer patients, according to findings of the NRG Oncology/NSABP B-42 trial presented at the San Antonio Breast Cancer Symposium (SABCS 2016) held in Texas, US. 

Jackey Suen, 21 Dec 2016

Adding everolimus to fulvestrant in second-line treatment of hormone receptor (HR)-positive, HER2-negative advanced breast cancer improves progression-free survival (PFS) by 40 percent, the phase II PrECOG 0102 study has shown. [SABCS 2016, abstract S1-02]