Assay Accurately Predicts Tx Response in Ovarian Cancer

Roxanne Nelson

August 21, 2013

A new assay appears to be able to accurately predict chemotherapy response in ovarian cancer, and as a result, improves both overall and progression-free survival.

Women who were treated with a chemotherapy agent identified as sensitive by the ChemoFx drug response assay (Precision Therapeutics, Inc) survived 14 months longer as compared with those treated by nonsensitive chemotherapies identified by the assay.

The finding comes from a 262-patient study published online August 13 in Gynecologic Oncology and sponsored by the manufacturer.

"This clinical study is a landmark for the treatment of ovarian cancer because it is the first prospective data that definitively shows that a personalized diagnostic test can make a significant clinical impact by improving overall survival by 65% in women with this devastating cancer," lead author Thomas J. Rutherford MD, PhD, professor of obstetrics and gynecology and reproductive sciences and section chief of gynecologic oncology at the Yale School of Medicine in New Haven, Connecticut, said in a statement.

Patients treated with an assay-sensitive regimen had a median progression-free survival of 8.8 months compared with 5.9 months for those treated with regimens that were identified as intermediate or resistant by the assay (hazard ratio [HR] = 0.67, P = .009).

The authors also note that the association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs 0.66) and was independent of other covariates in multivariate analysis (HR = 0.66, P = .020).

Study Details

ChemoFx is currently commercially available and has been since 2006. According to the manufacturer, it is a drug-response marker and determines how an ovarian cancer patient's particular cancer cells may respond to different therapeutic agents. The assay provides the physician with both sensitivity and resistance information.

The study included 262 patients experienced with persistent, recurrent, or progressive epithelial ovarian, fallopian tube, or primary peritoneal cancer. Fresh tissue samples were collected for chemoresponse testing. The participants were treated with 1 of 15 prospectively specified protocol treatments, according to their oncologist's medical judgment. Both patients and physicians were blinded to the assay results for the initial protocol treatment.

The primary endpoint of the study was progression-free survival; the secondary endpoint was overall survival.

Among women with platinum-sensitive cancer, carboplatin/paclitaxel (31%), pegylated liposomal doxorubicin (PLD) (15%), and carboplatin/gemcitabine (12%) were most frequently used. For those with persistent or platinum-resistant recurrent tumors, carboplatin/paclitaxel (29%), PLD (28%), and topotecan (13%) were the most common regimens.

The median follow-up time was 29 months across the cohort; median progression-free survival for the entire study population was 6.7 months. Median overall survival was 26.5 months. The median progression-free survival for platinum-sensitive and platinum-resistant patients were 9.3 months and 3.8 months (P < .001), respectively, whereas the median overall survival was 33.6 months and 21.8 months (P < .001), respectively.

Consistent Response, Useful Tool

The authors found that the association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs. 0.66). It was also independent of other covariates in multivariate analysis (HR = 0.66, P = .020).

They conclude that that the results of this study "are in notable contrast to multiple, randomized drug studies in this indication that have repeatedly shown little or no difference between various treatment regimens."

"Results from this study indicate that a chemoresponse assay may be a very useful tool for optimizing treatment selection when there are multiple clinically-acceptable and -equivalent treatments available, and few, if any, biological markers that can reliably assist in a more individualized treatment plan," they write. "When treatments are individualized, even though the same regimens are used clinically, patients experience marked improvements in outcome."

Unanswered Question

But this study leaves an important question unanswered, says an expert in the field.

"In reading the results of this trial, the well-known expression 'true, true, and unrelated' comes to mind," commented Maurie Markman, MD, senior vice president of clinical affairs and national director of medical oncology at the Cancer Treatment Centers of America in Philadelphia. Dr. Markman has a regular Medscape videoblog on oncology and was approached for independent commentary.

Dr. Markman pointed out that the study was a nonrandomized, prospective evaluation of survival outcomes, and ovarian cancer patients treated with a therapeutic regimen for whom "chemosensitivity testing" revealed the malignancy to be sensitive experienced superior progression-free and overall survival. But these patients were compared with patients who received a program in which the assay demonstrated the cells to have intermediate sensitivity or to be resistant.

"It is fair to state that this study result was both anticipated and has been previously reported with other chemosensitivity assay systems," Dr. Markman told Medscape Medical News. "However, what this study has not proven is that the outcome was the direct result of the use of a specific treatment program based on the assay result."

"In fact, it remains a completely open question as to whether patients with sensitive ovarian cancers do better than patients with resistant cancers essentially independent of whether 'regimen A' or 'regimen B' or 'regimen C,' and so on, is selected," he continued.

"So the question to be asked of these investigators and this company is whether they plan to conduct a study that actually answers the question of whether this assay can select the most effective regimen for a given cancer and not simply divide ovarian cancers into 'sensitive,' 'intermediate,' and 'resistant' groups with their corresponding statistically anticipated survival outcomes," Dr. Markman said.

The study was sponsored by Precision Therapeutics. All of the authors have a relationship with the manufacturer, either as a paid employee or as having received compensation for their participation in this clinical trial. Dr. Markman has disclosed financial relationships with Celligent; BIND Biosciences, Inc.; GlaxoSmithKline; Amgen; Boehringer Ingelheim; and Genentech.

Gynecol Oncol. Published online August 13, 2013. Full article

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