Results were presented at this years ASCO conference in Chicago from a third interim analysis of Study 19 that suggest an improvement in overall survival (OS) for patients with ovarian cancer treated with olaparib maintenance therapy following platinum-based chemotherapy.

Click here for an interview with Professor Jonathan Ledermann, director of the Cancer Research UK & UCL Cancer Trials Centre and lead author of Study 19 about the results.

These findings support the previously reported benefits of olaparib in progression-free survival (PFS) compared to placebo, the primary endpoint of the trial.

A 27% reduction in risk of death compared to placebo was seen in the overall trial population (HR 0·73, 95% CI 0·55–0·96, nominal p=0.02483; median OS 29·8 vs 27·8 months), with greater reduction in the risk of death of 38% compared to placebo observed in patients with BRCA1/2 mutations (BRCAm) (HR 0·62, 95% CI 0·41–0·94, nominal p=0.02480; 34·9 vs 30·2 months).

As this was the third analysis of survival, the nominal p-values did not meet the criterion for statistical significance and therefore the treatment effect observed for OS can only be considered descriptive.

A number of patients continue to benefit from olaparib maintenance therapy, with 15% of BRCAm patients receiving olaparib for over five years.

Professor Ledermann said, “These results are extremely encouraging. The data show that some ovarian cancer patients receive benefit from this treatment for over 5 years, which is significant for patients with limited treatment options.”

The data presented is based on a 77% data maturity conducted after more than five years total follow-up, with an additional three years of follow-up since the previous analysis.

Two interim analyses of OS from Study 19 have previously been conducted, at 38% data maturity (HR 0·94, 95% CI 0·63–1·39, p=0·75) and 58% data maturity (HR 0·88, 95% CI 0·64–1·21, p=0·44) in the overall trial population.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “These results are a testament to the value of olaparib’s mode of action and the potential significance of targeting the DNA damage response (DDR) pathway, reinforcing our commitment to explore the full potential of DDR targeted treatments across a range of cancers.”

DDR is a term describing the network of cellular pathways that minimise the daily impact of DNA damage.

Currently, many cancers are known to have defects in DDR pathways, which makes them dependent on and therefore, highly sensitive to inhibition of the remaining DDR pathways.

Targeting DDR deficiencies to preferentially kill cancer cells, while minimising the impact on normal cells, has potential for more selective, better tolerated therapies than chemotherapy that might improve survival in multiple cancers.

An extensive Phase III clinical trial programme investigating olaparib in BRCAm ovarian cancer patients (SOLO) is currently ongoing. Phase II and III studies in breast cancer, pancreatic cancer, and prostate cancer are also currently underway.

This update supports previously presented results on the primary endpoint of the trial of progression-free survival (PFS) which showed a statistically significant difference compared to placebo (HR 0·35, 95% CI 0·25–0·49, p<0.0001), with the greatest effect seen in the BRCAm subgroup (HR 0·18, 95% CI 0·10–0·31, p<0.0001).

A significant improvement in time to first subsequent therapy or death (TFST) (HR 0·32, 95% CI 0·22-0·48, p<0.00001) and time to second subsequent therapy or death (TSST) (HR 0·41, 95% CI 0·28-0·62, p<0.00001) was also observed with maintenance olaparib compared with placebo, consistent with previously reported data on TFTS and TSST.

There was no change to the overall safety profile and no new safety signals were reported for the patients remaining on treatment since the previous safety analysis.

Serious adverse events were reported in 25 (18%) of 136 patients in the olaparib group and 11 (9%) of 128 patients in the placebo group.

The most common serious adverse event was small intestinal obstruction (two [1%] patients in the olaparib group and three [2%] in the placebo group).

The most common adverse events in patients who were treated for two years or more were nausea (olaparib: 24 patients [75%] vs placebo: 2 patients [40%]), fatigue (18 [56%] vs 2 [40%]), constipation (12 [38%] vs 1 [20%]) and vomiting (12 [38%] vs 0).

These long-term safety findings are consistent with previous data from Study 19 and other clinical olaparib monotherapy studies.

Source: ASCO 2016