PAOLA-1: What the Ovarian Cancer Trial Found

What maintenance therapy is trying to do

Advanced ovarian cancer usually responds to first treatment. Surgery and platinum-taxane chemotherapy shrink it, often dramatically.

Then it comes back. That is the pattern the field has been fighting for decades.

Maintenance therapy is the attempt to hold the line. After the initial treatment has worked, a drug is continued to delay the return. PAOLA-1 tested one such combination.

Two drugs with unrelated mechanisms

Olaparib is a PARP inhibitor. PARP is an enzyme that repairs single-strand breaks in DNA. Block it and those breaks accumulate.

Healthy cells manage, because they have a second repair system called homologous recombination. Cells that have lost that backup, including tumors with BRCA mutations, cannot cope with both failures at once, and they die. That principle is called synthetic lethality.

Bevacizumab works on the blood supply instead. It binds VEGF, the signal tumors use to grow new vessels, and blocks it from reaching its receptors.

Bevacizumab was already part of standard first-line care for these patients. PAOLA-1 asked what adding olaparib on top would do.

The trial

PAOLA-1 was a randomized, double-blind, international phase 3 trial. Double-blind means neither patients nor investigators knew who received which pill.

Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were responding after first-line platinum-taxane chemotherapy plus bevacizumab. Crucially, they were eligible regardless of surgical outcome and regardless of BRCA mutation status.

Of 806 patients randomized 2 to 1, 537 received olaparib tablets at 300 milligrams twice daily and 269 received placebo, each for up to 24 months. Everyone continued bevacizumab at 15 milligrams per kilogram every three weeks for up to 15 months in total.

The primary endpoint was the time from randomization until investigator-assessed disease progression or death.

What happened

After a median follow-up of 22.9 months, median progression-free survival was 22.1 months with olaparib plus bevacizumab against 16.6 months with placebo plus bevacizumab. The hazard ratio was 0.59, with a 95 percent confidence interval of 0.49 to 0.72, and a p-value below 0.001.

A hazard ratio below 1 favors the combination. At 0.59 the rate of progression or death ran about 41 percent lower.

The subgroup that drove it

The overall result understates what happened in part of the group, and overstates it in the rest.

Homologous recombination deficiency, or HRD, describes tumors that have lost the DNA repair backup olaparib depends on. BRCA mutations are one cause; there are others.

In HRD-positive tumors, including those with BRCA mutations, the hazard ratio was 0.33, with median progression-free survival of 37.2 months against 17.7. That is more than a doubling.

In HRD-positive tumors without a BRCA mutation, the hazard ratio was 0.43, with median progression-free survival of 28.1 months against 16.6.

That second figure is the one the trial existed to produce. Before PAOLA-1, PARP inhibitor maintenance was largely a BRCA question. This showed benefit extending to HRD-positive tumors that are not BRCA-mutated, which is a larger group. Our page on HRD-positive ovarian cancer explains how that status gets established.

Side effects were consistent with what was already known about both drugs.

When to get checked

Ovarian cancer is the reason the phrase "silent killer" persists, and NCI's wording is stark. It may not cause early signs or symptoms, and when symptoms do appear the cancer is often advanced.

NCI lists these:

• Pain, swelling, or a feeling of pressure in the abdomen or pelvis.
• A sudden or frequent urge to urinate.
• Trouble eating, or feeling full quickly.
• A lump in the pelvic area.
• Gas, bloating or constipation.

Every one of those is also ordinary. That is the problem.

NCI's own rule is the usable one: if the signs get worse, or do not go away on their own, check with a doctor. Persistent bloating that is new and daily for two or three weeks, rather than the kind that comes and goes with meals, is the pattern worth taking in. Our page on ovarian cancer symptoms covers what happens next.

Assessment involves a pelvic exam, in which the doctor feels the size, shape and position of the uterus and ovaries, and a CA-125 blood test, which measures a substance released by ovarian cancer cells and by some benign conditions.

The survival picture

The American Cancer Society projects 21,010 new US ovarian cancer cases and 12,450 deaths for 2026. Median age at diagnosis is 63.

Five-year relative survival for 2016 to 2022 cases is 52.0 percent overall. By spread at diagnosis it is 91.9 percent while confined to the ovary, 70.1 percent with regional lymph nodes involved, and 31.5 percent for distant disease.

The distribution explains the gap between those numbers and the headline. Only 22 percent are found localized. Fifty-four percent are already distant.

These are registry averages describing a population, not a person, and they cover every ovarian cancer type at every treatment era in the window.

What this trial cannot tell you

The endpoint was progression-free survival, not overall survival. Delaying progression is not the same as living longer, and the published result does not answer the second question.

Everyone in both arms received bevacizumab. The trial tests what olaparib adds to bevacizumab, not olaparib against bevacizumab, and not either against nothing.

The benefit is concentrated. HRD-positive tumors did far better than the overall figure suggests, which means HRD-negative tumors did worse than it suggests. That test result changes the meaning of the whole trial for an individual.

Everyone had already responded to first-line chemotherapy. People whose cancer did not respond are outside the trial entirely.

And maintenance means up to 24 months of daily tablets while feeling relatively well. Whether that trade is worth making is a personal judgment, not a statistical one. Our page on maintenance therapy after ovarian cancer treatment sets out the alternatives.

Sources

• Ray-Coquard I and others, Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer, New England Journal of Medicine 2019 (record and abstract via NCBI) — https://pubmed.ncbi.nlm.nih.gov/31851799/
• NCI PDQ, Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (Patient Version) — https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq
• SEER Cancer Stat Facts, Ovarian Cancer — https://seer.cancer.gov/statfacts/html/ovary.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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