Jean-Marc Classe, MD, PhD

Regardless of whether patients with advanced epithelial ovarian cancer without suspicious lymph nodes underwent primary surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery, retroperitoneal lymphadenectomy (RPL) did not provide a survival benefit in the Phase 3 CARACO trial (NCT01218490), which further highlights the role of RPL in this patient population, according to Jean-Marc Classe, MD, PhD.

Findings from the study presented at the ASCO Annual Meeting 2024 found that patients who received RPL (n = 186) had a median progression-free survival (PFS) of 18.5 months versus 14.8 months in patients who did not receive RPL (n = 193; HR 0.96; 95% CI 0.77-1.20; P = .712). The median overall survival (OS) was 58.8 months for those who received RPL versus 48.9 months for those who did not receive RPL (HR 0.92; 95% CI 0.72-1.17; P = .489).

“The original aim of the study was to establish the superiority of lymphadenectomy, and in the end we found no difference in survival between the two arms,” ​​Classe explained in an interview with OncLive®.

In the interview, Classe discussed the rationale for investigating the role of RPL in patients with advanced ovarian cancer without suspicious lymph nodes, discussed data from CARACO in detail, and explained the implications of the findings.

Classe is head of the Department of Oncological Surgery at the University of Nantes in France.

OncLive: What is the current role of lymphadenectomy in patients with advanced epithelial ovarian cancer who undergo cytoreductive surgery after neoadjuvant chemotherapy?

Class: The (current) treatment of patients with advanced ovarian cancer is primary surgery when complete primary surgery is possible; or (patients receive interval cytoreduction) surgery after neoadjuvant chemotherapy when primary surgery is not possible. This is an important distinction.

The CARACO study referred to patients who did not have suspicious lymph nodes on CT scan or during surgery when the surgeon palpated the area where we find the lymph nodes around the (para-aortic) vessels or the pelvic vessels. If large nodes are present, there is an indication for lymphadenectomy. However, the CARACO study referred to patients without suspicious lymph nodes.

What were the characteristics of the patient group participating in this study and how was the study designed?

We included patients with advanced epithelial ovarian cancer at FIGO stage III or IVA. Stage IVA is pleural effusion without metastases. It was important to select this population and it was important that patients did not show (signs of) suspicious lymph nodes on a CT scan (at baseline).

What key findings from this study were presented at the 2024 ASCO Annual Meeting?

It is important to note that we had a high rate of patients with complete surgery (without residual disease): 85.6% in the no-RPL group versus 88.3% in the RPL group. Approximately one-quarter of patients underwent primary surgery and three-quarters underwent interval cytoreductive surgery after neoadjuvant chemotherapy.

The lymphadenectomy arm experienced greater toxicity, including transfusion or blood loss (39.3% with RPL vs. 29.7% with no RPL), reintervention (8.3% vs. 3.1%), and postoperative death (1.1% vs. 0.5%).

We did not see any difference in PFS (or OS between arms). Since PFS was the primary endpoint and OS was the secondary endpoint, this was a negative study. This is important because CARACO was originally a superiority study. The aim was to establish the superiority of (added) lymphadenectomy, and in the end we did not see any differences in survival between the two arms.

How might these findings influence future considerations of lymphadenectomy in patients with advanced ovarian cancer who do not have suspicious lymph nodes?

In the area of ​​lymphadenectomy in patients with advanced ovarian cancer who do not have suspicious lymph nodes, we already had the LION trial (NCT00712218). (Data from) the LION trial were presented as an oral presentation at the 2017 ASCO Annual Meeting and (later) at the New England Journal of MedicineThe LION trial (data) showed no difference in PFS (with lymphadenectomy vs. no lymphadenectomy) in patients treated with primary surgery.

LION was similar to the CARACO trial in terms of primary surgery; however, the (current) standard treatment of these patients included both primary surgery and surgery after neoadjuvant chemotherapy. LION only included patients treated after primary surgery. The CARACO trial provides additional information and was also a negative (trial). The data showed no benefit of performing lymphadenectomy in patients treated with neoadjuvant chemotherapy and surgery; however, this only applies to patients who did not have suspicious lymph nodes before surgery.

reference

Classe JM, Campion L, Lecuru F, et al. Avoiding lymphadenectomy in patients with advanced epithelial ovarian cancer treated with primary or interval cytoreductive surgery after neoadjuvant chemotherapy: the randomized CARACO phase III trial. J Clin Oncology. 2024;42(Supplement 17):LBA5505. doi:10.1200/JCO.2024.42.17_suppl.LBA5505