Joan H. Schiller, MD

JOAN H. SCHILLER, MD, Deputy Director of Inova Schar Cancer Institute in Fairfax, Virginia, pointed out that no one particular chemotherapy regimen has been shown to improve overall survival vs other standard regimens. “So if we can’t identify one best chemotherapy, what else can we do to make chemotherapy better?” she asked. “These researchers looked at the DNA-repair pathway as one possibility.” 

Although the study showed that BRCA1 is not a predictive biomarker for treatment efficacy, there were some interesting findings, including a “pretty impressive survival difference” by treatment regimen in patients with low levels: 74 months with cisplatin/gemcitabine vs 40 months with cisplatin/docetaxel (hazard ratio = 0.62; P = .005). “Patients with low levels probably do better when the cisplatin is combined with gemcitabine than docetaxel,” she noted. 

But Dr. Schiller noted that the low BRCA1 cohort had more adenocarcinomas, more females, and more never-smokers—good-prognosis factors. However, it is possible that the substitution of gemcitabine for taxane yielded a regimen to which low expressors would be more sensitive, she said. 

Questions Remain 

Dr. Schiller noted the results in the intermediate and high expressors in the experimental arms were to be expected, but she cautioned against drawing conclusions based on small numbers of patients in a trial not designed for noninferiority. She also questioned whether SCAT’s design was optimal for studying the questions it posed. 

Most important, in patients with high BRCA1 levels, the lack of a major difference between the control arm (cisplatin/docetaxel) and docetaxel alone raises the question of whether cisplatin is needed at all in this subgroup, she commented. 

In this study, BRCA1 was clearly confirmed as a prognostic factor, but still unclear is whether its expression is more important in determining the role of a platinum agent in this population. Certainly, BRCA1 expression should be a stratification factor in future studies, she added. 

“But what we don’t need is more randomized studies looking for predictive DNA-repair enzymes as biomarkers for cisplatin,” she maintained. “Though further studies are needed to explore the role of BRCA1 as a predictive marker for lack of response to a taxane.” 

Dr. Schiller applauded the investigators for their “major contribution to the field of DNA repair” and commented: “They took preclinical findings and carried them to their natural conclusion in phase I, II, and III studies. That’s not easy thing to do for investigator-initiated clinical trials.” ■

DISCLOSURE: Dr. Schiller reported no conflicts of interest.