Trial shows efficacy over chemotherapy alone for this patient population

Secondary cytoreduction followed by chemotherapy improved progression-free survival (PFS) compared with chemotherapy alone for patients with platinum-sensitive, relapsed ovarian cancer who were selected for surgery based on their international iMODEL score plus PET-CT imaging results, the phase III SOC-1 trial found.

At a median follow-up of 36 months (interquartile range (IQR) 18.1-58.3 months), median PFS was 42% longer at 17.4 months (95% CI, 15.0-19.8 months) in the surgery group compared with 11.9 months (95% CI, 10.0-13.8 months) in the no surgery group at a hazard ratio (HR) of 0.58 (95% CI, 0.45-0.74; P<0.0001), Tingyan Shi, MD, Zhongshan Hospital, Furdan University, Shanghai, China, and colleagues reported in The Lancet Oncology.

Overall survival (OS) data were still immature at the time of publication — however, in a preplanned interim analysis, median OS between the two groups was very similar at 58.1 months (95% CI, not estimable to not estimable) in the surgery group compared with 53.9 months (95% CI, 42.2-65.5 months) in the no surgery group, Shi and colleagues added. Morbidity was “acceptable” in patients randomized to secondary cytoreduction, they also noted.

“Secondary cytoreduction is a widely practiced, but controversial, option for patients with platinum-sensitive relapse,” Shi and colleagues wrote. “The results of this trial support the efficacy of secondary cytoreduction in patients with relapsed ovarian cancer selected using iMODEL scores and PET-CT imaging.”

The SOC-1 study was carried out at four primarily academic sites in China and involved 357 patients, 182 of whom were assigned to the surgery group and 175 of whom received chemotherapy alone. Among other factors, patients were stratified by their iMODEL score of less than 4.7 or 4.7 or greater. Patients in both groups received either surgery or chemotherapy within 4 weeks after randomization. However, the median time between randomization and secondary cytoreduction was 7 days (IQR, 5-8 days), the authors noted. The median time between surgery and the initiation of chemotherapy was 16 days (IQR, 13-21 days) in the surgery group while the median time between randomization and initiation of chemotherapy in the no surgery group was 2 days (IQR, 1-4 days).

“For both treatment groups, recommended chemotherapy was a platinum-based regimen, with six 3-weekly cycles of intravenous paclitaxel (175 mg/m2) or docetaxel (75 mg/m2) combined with intravenous carboplatin (area under the curve [AUC] of 5 mg/mL per min),” Shi and colleagues detailed. That said, 20% of patients assigned to the surgery group and 26% of patients in the no surgery group received fewer than 6 cycles of chemotherapy due to disease progression.

Targeted maintenance therapy was allowed in SOC-1 with either bevacizumab (Avastin, Roche Canada) or a poly (ADP-ribose) polymerase (PARP) inhibitor and surgery was also allowed on subsequent relapse. However, only 10% of SOC-1 patients received maintenance therapy, most of which was with a PARP inhibitor.

Importantly, when the database was locked in mid-December 2019, 37% of patients randomized to the no surgery arm subsequently relapsed and underwent secondary cytoreductive surgery.

Based on the iMODEL score, rates of complete resection differed. In patients with an iMODEL score of less than 4.7, 79% assigned to surgery had a complete resection compared to only 61% of those with an iMODEL score of more than 4.7 who were similarly assigned to surgery.

Some 5% of patients in the surgery group experienced grade 3 to 4 surgical morbidity at 30 days postoperatively but no patient in either group had died some 60 days after receiving their assigned treatment. Rates of grade 3 to 4 adverse events (AEs) during chemotherapy were relatively low and were largely hematologic in nature.

Almost all patients in both groups received second-line intravenous chemotherapy, the study authors noted.

Commenting on SOC-1’s findings, Debra Richardson, MD, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, pointed out that SOC-1 was actually one of 3 randomized, phase III trials evaluating secondary debulking followed by a platinum-based chemotherapy regimen versus chemotherapy alone in patients with their first recurrence of platinum-sensitive ovarian cancer.

And in fact, the median PFS among patients who underwent secondary cytoreduction was similar between all 3 trials at 18.4 months in DESKTOP III and 18.9 months in GOG-0213, compared with 17.4 months in SOC-1 surgery counterparts.

However, only DESKTOP III met its primary endpoint of an overall survival advantage of almost 16 months with secondary cytoreduction whereas the no surgery group in GOG-0213 had an overall survival advantage some 14 months longer than the surgery group.

Given that 37% of patients initially assigned to the no surgery group in SOC-1 crossed over and had secondary debulking surgery, OS results from the current study may well be compromised, Richardson speculated. “Surgical trials are difficult to complete,” Richardson wrote.

For example, it took SOC-1 investigators almost 7 years to complete enrollment of 357 patients while it took GOG-0213 investigators almost 10 years to enroll 485 patients.

DESKTOP III investigators did better, enrolling 407 patients in 4 years but the SOCcer trial in the Netherlands closed prematurely due to poor accrual having only enrolled 12% of 230 planned patients in 5 years.

“Biases clearly exist when it comes to willingness to randomly assign patients to surgery versus no surgery,” Richardson wrote.

Furthermore, most of the women enrolled in these 3 trials had a platinum-free interval of over 12 months, suggesting that results might not be generalizable to all women with platinum-sensitive, recurrent ovarian cancer.

Perhaps most importantly, treatment for ovarian cancer is rapidly changing, as women with advanced ovarian cancer are now eligible for front-line maintenance therapy with bevacizumab, PARP inhibitors, or combination maintenance. “How these maintenance strategies might affect the validity of the models to predict resectability that have been developed is unknown,” Richardson pointed out, “because maintenance therapy for upfront ovarian cancer was not commonplace when these models were developed.”

Richardson also emphasized that patients who have incomplete secondary cytoreductive surgery are harmed by it—median OS was lower in all 3 randomized, phase 3 studies for women who underwent secondary cytoreduction than those who did not undergo surgery.

“Therefore, ideally more predictive models will be developed, and preoperative PET-CT scans should be considered to exclude patients who are unlikely to be completely resected,” she advised, adding that if surgeons are considering offering secondary cytoreductive surgery, either the iMODEL or DESKTOP III criteria should be used to identify patients who are appropriate for such surgery.

  1. Secondary cytoreduction followed by chemotherapy improved progression-free but preliminarily, not overall survival in patients with platinum-sensitive, relapsed ovarian cancer when selected for surgery based on their international iMODEL score plus PET-CT imaging.

  2. Be aware that women with advanced ovarian cancer are now eligible for front-line maintenance therapy and how maintenance therapy will affect the validity of models to predict resectability in this patient population is not yet known.

Pam Harrison, Contributing Writer, BreakingMED™

The study was funded by the Zhongshan Development Program.

SOC-1 authors had no conflicts of interest to declare.

Richardson declared she has received personal fees from AstraZeneca, Genentech, Foundation Medicine, Tesaro/GlaxoSmithKline, Bayer, Mersana, and Deciperha.

Cat ID: 692

Topic ID: 78,692,730,692,693,192,925