Objectives

In locally-advanced cervical cancer (LACC), platinum-based chemoradiotherapy (CRT) has been the standard- of-care treatment for >20 years. CALLA is the first global Phase 3 study evaluating immune checkpoint inhibition (durvalumab) versus placebo in combination with and following CRT in LACC (NCT03830866).

Methods

Newly-diagnosed, untreated patients with LACC (FIGO 2009 stages IB2–IIB node positive, IIIA–IVA with any node status) were randomized 1:1 to durvalumab (1500 mg IV) or placebo Q4W, for a total of up to 24 months, in combination with and following CRT. CRT comprised concurrent weekly IV cisplatin with EBRT and brachytherapy. RT quality was monitored, with variations evaluated for clinical significance. The primary endpoint is PFS; secondary endpoints include OS, objective response rate, local/distant disease progression incidence, and safety.

Results

770 patients were randomized (N=385 per arm) at 120 sites in 15 countries. Median age was 49 years; median follow-up was 18.5 months.

Durvalumab+CRT did not show a statistically significant improvement in PFS vs placebo+CRT (HR 0.84 [95% CI, 0.65-1.08]; P=0.174); there was no detriment to OS, although data were immature and not formally tested.

Adverse events of grade 3–4 occurred in 51.7% and 51.0% of patients in the durvalumab+CRT and placebo+CRT arms, respectively; 12.5% and 9.6% of patients discontinued treatment due to AEs possibly related to study drug.

Conclusions

Durvalumab in combination with and following CRT did not significantly improve PFS in patients with LACC. Safety of durvalumab+CRT was generally comparable to CRT alone, with no new or unexpected toxicity.

Funding: AstraZeneca

Objectives

To evaluate the feasibility of uterine transposition (UT) as a method of preserving ovarian and uterine function after pelvic radiation.

Methods

This was a prospective, non-randomized feasibility study of UT for patients with non-gynecologic pelvic cancers, who require radiation. UT to the upper abdomen was performed 7 to 14 days prior radiation. Frequent clinical examinations and doppler ultrasound were used to evaluate the gonadal vessels vasculature after surgery. The uterus was placed back to the pelvis 2 to 4 weeks after radiation and patients were followed with clinical examinations, pelvic ultrasound and laboratory tests to evaluate hormonal function. Menses were systematically recorded. Cancer treatment and follow-up were performed according to the standard guidelines and no modification were allowed.

Results

From June 2017 to June 2019, eleven patients were selected for the study. Eight patients were submitted to UT (median age of 30.5 yo). There were no transoperatory complications. Cervical stenosis was the most common postoperative complication. One patient had uterine necrosis 4 days after surgery, but the right ovary was preserved and kept normal hormonal function. One patient died from carcinomatosis 4 months after UT. All patients who preserved the uterus have normal hormonal levels, menses and sexual activity after treatment. Two patients have had spontaneous pregnancies, one baby was born at 37 weeks and the other patient is 20 weeks pregnant. One patient tried to get pregnant but did not succeed.

Conclusions

Uterine transposition is a feasible procedure to preserve the uterus and gonadal function. Spontaneous and healthy pregnancy is also possible.

Objectives

Methods

Results

Conclusions

Objectives

In ARIEL3 (NCT01968213), rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo. We present updated PFS2 and preplanned final overall survival (OS) analyses.

Methods

Patients were randomized to receive rucaparib 600 mg BID or placebo. Efficacy was analyzed across the 3 protocol-defined nested cohorts (BRCA-mutant, homologous recombination deficient [HRD], and intent-to-treat [ITT]). PFS2 was an exploratory endpoint, defined as time from randomization to second event of investigator-assessed disease progression, or death due to any cause. OS was a secondary endpoint with analysis planned after 70% of death events. The data cutoff was April 4, 2022, for efficacy and December 31, 2019, for safety. Patients were followed after treatment discontinuation for incidence of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); MDS/AML are reported as of April 12, 2022.

Results

Median follow-up was 77.0 months as of the efficacy data cutoff. In the ITT population, death events had occurred in 410/564 (72.7%) patients. PFS2 and OS are presented in the Table. Among placebo-arm patients, ≈45% received a PARP inhibitor as a subsequent treatment. Safety was consistent with prior reports; MDS/AML was reported in 14 (3.8%) rucaparib-arm and 6 (3.2%) placebo-arm patients (P=0.72) (reported post-study drug treatment in 8 cases in the rucaparib arm and 6 in the placebo arm).

Conclusions

These data support the use of rucaparib as a maintenance treatment for recurrent ovarian carcinoma; although no OS benefit was seen, the PFS benefit for rucaparib was maintained through the subsequent line of therapy.

Objectives

This study investigates the selection criteria for omitting interval debulking surgery (IDS) after neoadjuvant chemotherapy (NACT) due to a higher response to chemotherapy for advanced ovarian cancer.

Methods

We searched the ovarian, fallopian, or primary peritoneal cancer database registered between January 2000 and May 2021. We included patients with clinical stage III to IV high-grade serous carcinoma of the ovary (HGSC) who received NACT after serial measurement of serum levels of CA-125 regardless of IDS. We calculated the CA-125 ELIMination of Rate Constant K (KELIM) value during two cycles of NACT. Then, we calculated the cut-off values of KELIM for predicting platinum resistance and then evaluated the effect of IDS on progression-free survival (PFS) and overall survival (OS) based on the values.

Results

Among 279 patients, 194 (76%) were treated with NACT/IDS, and 61 (24%) were treated with chemotherapy alone. Although NACT/IDS showed better PFS and OS than chemotherapy alone in patients with lower KELIM (<0.95), no difference in survival was shown in higher KELIM (≥0.95; Figure 1). In multivariate analysis, IDS was associated with better OS in Low KELIM patients (hazard ratio [HR], 0.517, p=0.016), while IDS was not associated with better survival in High KELIM patients (HR, 0.739, p=0.390). Also, radiologic complete response (CR) and partial response (PR) were associated with better survival regardless of KELIM score.

Conclusions

In conclusion, for stage III/IV HGSC patients presenting higher KELIM (≥0.95), IDS may be omitted when the radiologic CR or PR is accomplished during NACT.

Objectives

The aim of this study was to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (ICS) in clinical practice

Methods

This is a prospective, multicenter, cohort study, a total of 205 patients were enrolled. 9 patients were excluded, because they did not meet the inclusion criteria. We enrolled stage III/IV ovarian cancer who had at least three cycles of neoadjuvant chemotherapy followed by ICS either with or without HIPEC at seven Korean Gynecologic Oncology Group institutions between 2017 and 2021. The primary end point was progression-free survival (PFS). Overall survival (OS) and safety profile were key secondary endpoint.

Results

196 patients were included in this trial. 87 patients receive ICS without HIPEC and 109 patients receive ICS with HIPEC. The median duration of follow up was 28.2 months. 128 (65.3%) patients had disease recurrence and 30 (15.3%) patients had died. ICS with HIPEC was associated with significantly improved PFS (22.9 vs. 14.2 months; p = 0.005) and OS (not reached vs. 53.0; p = 0.002), compared with IDS without HIPEC. Grade III/IV postoperative complications were similar in the two groups (p = 1.000). Peritoneal recurrences were more common in ICS without HPEC compared to the ICS with HIPEC (41/64 [64.1%] vs 21/64 [32.8%], p = 0.001].

Conclusions

The incorporation of HIPEC to IDS resulted in longer PFS and OS than IDS alone without higher rates of side effects in advanced-stage ovarian cancer. Lower rate of peritoneal recurrence after HIPEC might have a prominent impact on OS.

Objectives

Despite recommendations for the integration of molecular classification in endometrial cancers (EC) into pathology reporting and clinical management, uptake is inconsistent. To assign ProMisE subtype, all molecular components must be available (POLE mutation status, MMR and p53 immunohistochemistry (IHC)) and often components are performed at different stages of care and/or at different centers resulting in diagnostic delays. We assess the performance of a one step DNA-based molecular classifier (ProMisE-2) compared to ProMisE.

Methods

DNA was extracted from ECs that had previously undergone molecular classification using ProMisE (POLE sequencing, IHC for p53 and MMR). ProMisE2 was derived using the Imagia Canexia Health Find It next-generation sequencing assay to assess mutations in POLE, TP53 and presence of microsatellite instability (MSI). Molecular subtypes assigned by ProMisE and ProMisE-2 were assessed for concordance metrics and the ability to recapitulate Kaplan-Meier survival curves.

Results

ProMisE-2 was assessed in 91 ECs with 2 cases failing sequencing coverage thresholds. 85/89 of cases were concordant with a kappa statistic 0.93 and an overall accuracy of 0.96. Five of six cases where ProMisE-2 was performed on matched biopsy and hysterectomy specimens were concordant. Molecular subtype assignment was associated with outcomes (PFS, DSS, OS) in both ProMisE and ProMisE-2 (Figure1).

Conclusions

We demonstrate high concordance of a one step DNA-based EC molecular classifier when compared to the original ProMisE classifier, importantly maintaining the prognostic value of ProMisE and presenting an option for centers where routine MMR and p53 IHC are not performed. Further validation is needed before implementation into clinical practice.