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Expert Point of View: Robert L. Coleman, MD


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Discussant of the DESKTOP III and SOC1 trials, Robert L. Coleman, MD, of U.S. Oncology Research in Woodlands, Texas, congratulated the authors of both trials. He put these results in perspective with the GOG-0213 study, which did not show a survival benefit for secondary surgery.

“There are general similarities of DESKTOP III and SOC1,” Dr. Coleman maintained. “Both studies used an algorithm to select surgical candidates. In DESKTOP III, the AGO criteria were used based on prior experience that a positive score was associated with a complete gross resection rate of about 74%. SOC1 used a modification of the integrated model scoring algorithm, which was previously demonstrated to provide prognostic value and was associated with a complete gross resection rate of more than 50%. Both trials included patients with predominantly advanced-stage, high-grade, serous histology, although women entering DESKTOP III had a slightly longer platinum-free interval, measured from the last platinum-based therapy regardless of maintenance therapy,” Dr. Coleman said.

Robert L. Coleman, MD

Robert L. Coleman, MD

“Reflecting the validity of the decision algorithms for surgical candidacy, both trials were associated with a complete gross resection rate of over 74% and had low overall postoperative mortality,” he continued.

Comparison With GOG-0213

“Although DESKTOP III alone met the primary endpoint of overall survival, both studies demonstrated an added benefit in progression-free survival,” Dr. Coleman noted. “Both investigators support that the use of a triage algorithm to select patients for surgery may lead to complete resection in nearly 75% of patients. However, the price paid for being wrong is substantial, with no benefit seen in progression-free survival and possibly a detriment in overall survival.”

In contrast, GOG-0213 enrolled nearly 1,000 patients to answer two questions, according to Dr. Coleman: “Is there an overall survival value to adding bevacizumab maintenance vs paclitaxel/carboplatin alone in platinum-sensitive patients? Does secondary cytoreduction in this patient population improve overall survival. The study answered the first question with a ‘yes’ but failed to show an overall survival benefit with surgery.”

“Surgery in GOG-0213 was left to the discretion of the investigator, with guidance that eligible patients should be considered amenable to complete gross resection based on clinical parameters and imaging,” Dr. Coleman explained. The gross resection rate was achieved in slightly fewer patients (67%) in GOG-0213 than in DESKTOP III and SOC1. Dr. Coleman also noted bevacizumab was used in substantially more patients in GOG-0213 (84%) than in the other two trials and “may have be an equalizer against the impact of surgery.” He added: “Recall that we showed in GOG-0213’s first primary objective that adding bevacizumab to paclitaxel/carboplatin followed by bevacizumab maintenance improved both progression-free and overall survival. Patients participating in GOG-0213’s second primary objective assessing secondary surgery benefited from this information, and that remains the most striking difference between GOG-0213 and DESKTOP III and SOC1.”

“There are some takeaway points from these three prospective trials. Criteria for patient selection are probably best represented by one of the validated algorithms. However, median survival and 3-year overall survival rates in the patients undergoing surgery in this setting are remarkably consistent among the three trials. Despite the slightly more prognostically favorable patient populations in DESKTOP III and SOC1, both trials have similarly performing control arms. The outlier is GOG-0213’s control arm, where the median overall survival was 65.7 months with concomitant and maintenance bevacizumab, which outperformed arms where it was not used and appears to outperform the control arms of both DESKTOP III and SOC1,” Dr. Coleman noted.

DISCLOSURE: Dr. Coleman has served as a consultant or advisor to Clovis Oncology, Genentech/Roche, Esperance, AstraZeneca/MedImmune, Genmab, GamaMabsPharma, Tesaro, OncoMed, Sotio, Oncolytics, and AbbVie; has received reimbursement for travel, accommodations, and expenses from Merck, AstraZeneca/MedImmune, Array Biopharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG-Partners, Sotio, and Vaniam Group; and has received research funding from AstraZeneca/MedImmune, Esperance, OncoMed, Array, Clovis Oncology, Johnson & Johnson, Merck, Roche/Genentech, Abbott/AbbVie, and GOG Foundation.

 


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