medwireNews: Adding olaparib to paclitaxel does not improve survival among Asian patients with advanced gastric cancer that has progressed during or after first-line therapy, show results of the phase III GOLD trial.
The study therefore did not meet its primary objective of confirming previous phase II data (Study 39) that demonstrated a significant improvement in overall survival (OS) among patients receiving the combined therapy compared with those receiving paclitaxel alone.
The reasons for this are “uncertain” but may be due to underdosing and setting expectations of treatment effect too high, Yung-Jue Bang (Seoul National University College of Medicine, South Korea) and co-investigators remark.
They report in The Lancet Oncology that median OS in the current study was 8.8 months among the 263 patients (mean age 58 years, 66% men) with pretreated advanced gastric cancer who were randomly assigned to receive olaparib (100 mg twice daily) plus paclitaxel (80 mg/m2 intravenously) until disease progression or discontinuation.
This was not significantly longer than the 6.9-month median OS period observed among the 262 patients (mean age 59 years, 71% men) randomly assigned to receive placebo plus paclitaxel.
There was also no significant difference in OS among the 94 patients with ataxia-telangiectasia mutated protein (ATM)-negative tumors. In this group, median OS was 12.0 months with olaparib (n=48) and 10.0 months with placebo (n=46).
In spite of this, Bang et al say that the study generated important safety data concerning the use of olaparib alongside a chemotherapeutic agent.
Olaparib plus paclitaxel was well tolerated by the patients, with neutropenia, leukopenia, and decreased neutrophil count being the most commonly reported grade 3 or worse adverse events, occurring in 30%, 16%, and 16% of patients, respectively.
Neutropenia and leukopenia were also the most common grade 3 or worse adverse events in the placebo plus paclitaxel group, reported in 23% and 10% of patients, respectively, along with decreased white blood cell count, which occurred in 8% of patients.
The researchers conclude that although the GOLD study did not meet its primary objective, “[o]laparib continues to be investigated in a wide-reaching clinical programme in a variety of tumour types and patient populations, especially in patients with homologous recombination repair deficiencies.”
In an accompanying comment, Elizabeth Smyth, from the Royal Marsden Hospital in London, UK, says that key differences between GOLD and Study 39 might explain the lack of survival benefit with olaparib in the phase III trial.
In particular, 51% of patients in Study 39 were ATM negative compared with 18% –reflecting population prevalence – in GOLD.
“The promising overall survival of olaparib-treated ATM-negative patients in Study 39 might have inflated the results for the overall population, leading to an over-optimistic prediction of the benefit from olaparib in GOLD,” she writes.
By Laura Cowen
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