SOC-1 Adds Support For Cytoreduction Strategy For Relapsed Platinum-Sensitive Ovarian Cancer

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: For women with potentially resectable relapsed epithelial ovarian cancer, progression-free survival (PFS) is significantly longer with secondary cytoreduction followed by platinum chemotherapy than with chemotherapy alone, say the SOC-1 trial investigators. 

The team suggests that this approach might become the recommended standard of care at specialised centres for patients with a high probability of achieving complete resection, as determined by favourable positron emission tomography–computed tomography (PET–CT) imaging and an iMODEL score no higher than 4.7 out of a possible 11.9 points. 

The iMODEL score is derived from FIGO stage, residual disease status after primary surgery, duration of platinum-free interval, ECOG performance status, and, at time of recurrence, serum CA125 level and the presence of ascites, explain Rongyu Zang, from Zhongshan Hospital in Shanghai, China, and co-workers. 

The phase III open-label study recruited relapsed patients who had received their first-line platinum-based chemotherapy at least 6 months beforehand and had met the iMODEL and PET–CT criteria, although a later protocol amendment also permitted patients with an iMODEL score above 4.7 points in combination with a CA125 level of more than 105 U/mL to undergo secondary cytoreduction if imaging indicated resectable disease, the researchers say. 

As reported in The Lancet Oncology, median PFS was 17.4 months for the 182 patients who were randomly assigned to receive secondary cytoreductive surgery followed by six cycles of carboplatin given with paclitaxel or docetaxel every 3 weeks. 

This was significantly longer than the 11.9 months achieved by the 175 patients who received chemotherapy without surgery, giving a hazard ratio for progression or death of 0.58 in favour of the surgical arm. 

Interim analysis of overall survival showed a trend in favour of secondary cytoreduction, at a median 58.1 versus 53.9 months with chemotherapy only, but this did not reach statistical significance. 

Rongyu Zang and co-authors note that the study design allowed 37% of the 130 patients in the chemotherapy-only arm who experienced further relapses to undergo cytoreductive surgery, which might “extend the median overall survival in the no surgery group and lead to reduced statistical power to detect a negative result in overall survival.” 

They therefore plan to follow patients for accumulating treatment-free survival, as well as continuing to monitor overall survival until the data mature. 

Of note, 5% of the surgical patients experienced grade 3 or 4 surgical morbidity within 30 days of their procedure. The most common chemotherapy-related grade 3–4 adverse events were similar in the surgical and chemotherapy-only arms, such as neutropenia (17 vs 12%), leukopenia (8 vs 5%) and anaemia (6 vs 6%).  

There were no treatment-related deaths in either arm. 

“All patients should be counselled about the options of secondary cytoreduction in specialised centres with high volumes of ovarian cancer surgery”, the team therefore concludes. 

Debra Richardson, from the University of Oklahoma Health Sciences Center in Oklahoma City, USA, notes that secondary cytoreduction in the SOC-1 study achieved a similar median PFS to the DESKTOP III trial, which also used objective criteria to assess resectability, and the GOG-0213 study, which used investigator discretion to select patients for secondary cytoreduction. 

However, she remarks that “[b]iases clearly exist when it comes to willingness to randomly assign patients to surgery versus no surgery”, noting that most of the participants in the three trials had a platinum-free interval of at least 12 months despite the criteria requiring just 6 months.  

“Therefore, these results might not be generalisable to all women with platinum-sensitive recurrent ovarian cancer”, the commentator observes. 

Debra Richardson also highlights the “rapidly changing” treatment landscape for advanced ovarian cancer, with just 10% of SOC-1 participants given bevacizumab or PARP inhibitor maintenance therapy after platinum chemotherapy for relapsed disease. 

“How these maintenance strategies might affect the validity of the models to predict resectability that have been developed is unknown, because maintenance therapy for upfront ovarian cancer was not commonplace when these models were developed”, she writes. 

She adds: “The SOC-3 trial (NCT03983226) will address this question by incorporating niraparib maintenance into both surgery and no surgery groups.” 

References  

Shi T, Zhu J, Feng Y, et al. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol; Advance online publication 8 March 2021. https://doi.org/10.1016/S1470-2045(21)00006-1  

Richardson DL. Should we or should we not? Secondary debulking in ovarian cancer. Lancet Oncol; Advance online publication 8 March 2021. https://doi.org/10.1016/S1470-2045(21)00024-3