AstraZeneca and Merck & Co. won't easily surrender their lead in a class of targeted cancer therapies, thanks to positive data for the companies' drug Lynparza in an early-line ovarian cancer study.
When combined with chemotherapy and Roche's Avastin, Lynparza cut the risk of disease relapse or death by 41%, a result that a leading oncologist said was better than other results seen to date in this population of patients who've already responded to one round of chemo.
Results from the PAOLA-1 trial look close to being matched by data from AbbVie's experimental drug veliparib, which in a similar all-comers population cut the risk of disease progression by 32% when combined with chemo. Yet as an already marketed product, Lynparza will enjoy a quicker path to becoming standard treatment, and its edge in genetically-defined patients won't hurt it in a crowded field either.
Both Lynparza and veliparib are part of a class of drugs known as PARP inhibitors, which also includes GlaxoSmithKline's Zejula, Clovis Oncology's Rubraca and Pfizer's Talzenna. On Saturday, at the European Society for Medical Oncology meeting in Barcelona, AstraZeneca, AbbVie and GlaxoSmithKline all unveiled data from trials of their respective drugs in the first-line ovarian cancer maintenance setting.
These patients have experienced tumor shrinkage or complete remission following treatment with chemo. The PARP inhibitors plus chemo or, in Lynparza's case, chemo and Avastin, are intended to keep disease from returning.
Oncologists at the meeting got the uncommon opportunity to see data from three drugs from the same class being tested in similar populations.
All three trials enrolled patients whose disease had spread beyond the ovaries. At a minimum, tumor cells must have reached organs in the pelvis for patients to be enrolled, but the trials also included those who had tumors in distant organs. The studies of GSK's Zejula and AbbVie's veliparib first had patients undergo chemo, while the Lynparza trial required chemo plus Avastin first.
Among the broadest population tested in AbbVie's study, veliparib-treated patients lived a median 23.5 months without disease progression while patients on chemo alone lived 17.3 months. In GSK's PRIMA trial, Zejula-treated patients lived 13.8 months and patients on chemo alone lived 8.2 months without worsening.
Lynparza-treated patients, meanwhile, lived 22.1 months without return of disease or death, versus the 16.6 months for chemo patients in PAOLA-1.
Progression-free survival (months) and risk reduction versus control, in three ovarian cancer trials
|Drug||Study||BRCA mutation||HRD||Overall population|
|Veliparib||VELIA||34.7 months, 56%||31.9 months, 43%||23.5 months, 32%|
|Zejula||PRIMA||n/a||21.9 months, 57%||13.8 months, 38%|
|Lynparza||PAOLA-1||37.2 months, 69%||37.2 months, 67%||22.1 months, 41%|
SOURCE: ESMO, New England Journal of Medicine
Cross-trial comparisons should be treated with caution because of differences in the sizes of the studies and patient severity.
Nonetheless, the PAOLA-1 study should help cement Lynparza's place in this front-line setting. It is currently approved only for those patients with BRCA mutations who respond to chemo, in addition to other later-line indications.
"This study reports the greatest [risk reduction] and longest progression free survival we have ever seen," Isabelle Ray-Coquard, an investigator of the Lynparza PAOLA-1 study and professor at Claude Bernard University in France, said of the results. "In addition, [Lynparza] did not increase side effects compared to placebo."
Ray-Coquard reported receiving reimbursement from AstraZeneca for consulting, travel and accommodations. She also has worked with Clovis and Tesaro, the biotech GSK bought last year to get Zejula.
In patients with BRCA mutations, who have a higher risk of disease, and in those with homologous recombination deficiency, which makes tumor cells less able to repair themselves, Lynparza also appeared to outperform its rivals. Data showed AstraZeneca and Merck's drug reduced the risk of progression by 69% and 67%, respectively.
Lynparza is currently the top-selling PARP inhibitor, having recorded $520 million in sales in the first half of 2019 compared with $128 million for Zejula and $66 million for Clovis Oncology's Rubraca. The data emerging from ESMO suggest that gap is not likely to narrow anytime soon.