CARACO Data Add to Evidence Supporting Omission of Lymphadenectomy in Advanced Ovarian Cancer Without Suspicious Lymph Nodes

Irrespective 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), further clarifying the role of RPL in this patient population, according to Jean-Marc Classe, MD, PhD.

Findings from the study presented at the 2024 ASCO Annual Meeting indicated that patients who received RPL (n = 186) experienced a median progression-free survival (PFS) of 18.5 months vs 14.8 months for those who did not undergo 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 vs 48.9 months for those who did not (HR, 0.92; 95% CI, 0.72-1.17; P = .489).

“The trial’s initial aim was to detect a superiority of lymphadenectomy, and at the end, we didn't find any difference between the two arms in terms of survival,” Classe explained in an interview with OncLive®.

In the interview, Classe delved into the rationale for exploring the role of RPL in patients with advanced ovarian cancer without suspicious lymph nodes, expanded on data from CARACO, and detailed the implications of the findings.

Classe is head of the oncological surgery department at Nantes Université in France.

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

Classe: The [current] treatment for patients with advanced ovarian cancer is primary surgery, if complete primary surgery is feasible; or [patients receive interval cytoreductive] surgery after neoadjuvant chemotherapy if the primary surgery is not feasible. This is an important distinction.

The CARACO trial was about patients with no suspicious lymph nodes on their CT scan, or during the surgery when the surgeon performed palpation of the area where we find the lymph node around the [paraaortic] vessels or the pelvic vessels. If there [are] bulky nodes, there is an indication to perform a lymphadenectomy. However, the CARACO trial was for patients with no suspicious lymph nodes.

What were the characteristics of the patient population enrolled in this trial, and how was the study designed?

We included patients with advanced epithelial ovarian cancer that was FIGO stage III or IVA. Stage IVA is pleural effusion without metastasis. It was important to select this population, and it was important that patients show no [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's important to [note] that we had a high rate of patients with a complete surgery [without residual disease] at 85.6% in the no RPL arm vs 88.3% in the RPL arm. Approximately one quarter of patients [underwent] primary surgery, and three quarters [underwent interval cytoreductive] surgery after neoadjuvant chemotherapy.

We had more severe toxicity in the lymphadenectomy arm, including transfusion or blood loss [39.3% for RPL vs 29.7% for no RPL], reintervention [8.3% vs 3.1%], and postoperative death [1.1% vs 0.5%].

We didn't find any difference in PFS [or OS between the arms]. Considering PFS was the primary end point and OS was the secondary end point, [this was] a negative trial. That’s important because in the beginning, CARACO was a superiority trial. The aim was to detect superiority for [adding] lymphadenectomy, and at the end, we didn’t find any differences between the 2 arms in terms of survival.

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

In the field of lymphadenectomy for 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 at the 2017 ASCO Annual Meeting as an oral presentation and were [later] published in the New England Journal of Medicine. The LION trial [data] showed no difference in PFS [for lymphadenectomy vs no lymphadenectomy] in patients treated with primary surgery.

LION was similar to the CARACO trial regarding primary surgery; however, the [current] standard treatment for these patients included both primary surgery and surgery after neoadjuvant chemotherapy. LION only included patients treated after primary surgery. The CARACO trial brings additional information and was also a negative [trial]. Data showed no benefit to performing lymphadenectomy in patients treated with neoadjuvant chemotherapy and surgery; however, this is only for patients who had no suspicious lymph nodes before surgery.

Reference

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