Recurrent Gynecologic Malignancies Research Articles

Phase 1b study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis

Intravenous immune checkpoint blockade (ICB) has shown poor response rates in recurrent gynecologic malignancies. Intraperitoneal (i.p.) ICB may result in enhanced Tcell activation and anti-tumor immunity. In this phase 1b study, registered at Clinical. gov (NCT03508570), initial cohorts received i.p. nivolumab monotherapy, and subsequent cohorts received combination i.p. nivolumab every 2weeks and i.p. ipilimumab every 6weeks, guided by a Bayesian design. The primary objective was determination of the recommended phase 2 dose (RP2D) of the combination. Secondary outcomes included toxicity, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The trial enrolled 23 patients: 18 with ovarian cancer, 2 with uterine cancer, and 3 with cervical cancer. Study evaluable patients (n= 16) received a median of 2 prior lines of therapy (range: 1-8). Partial response was observed in 2 patients (12.5%; 1 ovarian, 1 uterine), and complete response was observed in 1 patient (6.3%) with cervical cancer, for an ORR of 18.8% (95% confidence interval: 4.0%-45.6%). The median duration of response was 14.8months (range: 4.1-20.8), with one complete response ongoing. Median PFS and OS were 2.7months and not reached, respectively. Grade 3 or higher immune-related adverse events occurred in 2 (8.7%) patients. i.p. administration of dual ICB is safe and demonstrated durable responses in a subset of patients with advanced gynecologic malignancy. The RP2D is 3mg/kg i.p. nivolumab every 2weeks plus 1mg/kg ipilimumab every 6weeks. This work was funded by Bristol Myers Squibb (CA209-9C7), an MD Anderson Cancer Center Support Grant (CA016672), the Ovarian Cancer Moon Shots Program, the Emerson Collective Fund, and a T32 training grant (CA101642).

Long-term outcomes of pelvic exenterations for gynecological malignancies: a single-center retrospective cohort study

BackgroundRecently, with the advancement of medical technology, the postoperative morbidity of pelvic exenteration (PE) has gradually decreased, and it has become a curative treatment option for some patients with recurrent gynecological malignancies. However, more evidence is still needed to support its efficacy. This study aimed to explore the safety and long-term survival outcome of PE and the feasibility of umbilical single-port laparoscopic PE for gynecologic malignancies in a single medical center in China.Patients and methodsPE for gynecological cancers except for ovarian cancer conducted by a single surgical team in Sun Yat-sen University Cancer Center between July 2014 and December 2019 were included and the data were retrospectively analyzed.ResultsForty-one cases were included and median age at diagnosis was 53 years. Cervical cancer accounted for 87.8% of all cases, and most of them received prior treatment (95.1%). Sixteen procedures were performed in 2016 and before, and 25 after 2016. Three anterior PE were performed by umbilical single-site laparoscopy. The median operation time was 460 min, and the median estimated blood loss was 600 ml. There was no perioperative death. The years of the operations was significantly associated with the length of the operation time (P = 0.0018). The overall morbidity was 52.4%, while the severe complications rate was 19.0%. The most common complication was pelvic and abdominal infection. The years of surgery was also significantly associated with the occurrence of severe complication (P = 0.040). The median follow-up time was 55.8 months. The median disease-free survival (DFS) was 17.9 months, and the median overall survival (OS) was 25.3 months. The 5-year DFS was 28.5%, and the 5-year OS was 30.8%.ConclusionPE is safe for patient who is selected by a multi-disciplinary treatment, and can be a curative treatment for some patients. PE demands a high level of experience from the surgical team. Umbilical single-port laparoscopy was a technically feasible approach for APE, meriting further investigation.

Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies.

Antibiotic use preceding immune checkpoint inhibitor (ICI) treatment has been associated with a decreased efficacy of ICI in solid tumors. In this study, we evaluated the effect of antibiotic use before ICI therapy on oncological outcomes. We examined patients with recurrent gynecologic malignancies at two academic institutions. The clinical data, including antibiotic use within 60 days of ICI initiation, type of antibiotics, reasons for antibiotic use, body mass index, tumor site, chemotherapy-free interval, prior history of radiotherapy, disease control rate (DCR), and overall survival (OS), were assessed. Of 215 patients, 22.9% (n = 47) received antibiotics before ICI treatment. The most common cancer was ovarian (52.1%, n = 112), followed by cervical (24.7%, n = 53) and endometrial (16.7%, n = 36). When we divided the cohort based on antibiotic use before ICIs, there were no significant differences in the DCR and baseline characteristics between the two groups. On multivariate analyses, the variables associated with poor OS were previous use of antibiotics for a cumulative duration of >14 days (HR 2.286, 95% CI 1.210-4.318; p = 0.011); Eastern Cooperative Oncology Group 2 or 3 (HR 4.677, 95% CI 2.497-8.762; p < 0.001); and chemotherapy-free interval of <6 months (HR 2.007, 95% CI 1.055-3.819; p = 0.034). Prior use of antibiotics for a cumulative duration of >14 days was associated with reduced survival in recurrent gynecologic malignancies.

ME07 Management of women with advanced and recurrent gynecologic malignancies

ME07 Management of women with advanced and recurrent gynecologic malignancies

Image-guided Interstitial Brachytherapy in the Treatment of Primary and Recurrent Vulvovaginal Gynaecological Malignancies

AimsTo evaluate the use, outcomes and toxicities of high dose rate brachytherapy (HDRB) to the vulvovaginal region in previously irradiated and radiotherapy-naïve patients for primary or recurrent gynaecological malignancies. Materials and methodsFrom January 2010 to December 2020, 94 women with a median age of 64 years (range 31–88 years) were treated with interstitial HDRB for vulvovaginal disease. Treatment details, including cumulative radiotherapy doses, were recorded together with reported toxicity, using Common Terminology Criteria for Adverse Events (CTCAE) grading. Dosimetric parameters, including D90, V100 and V150 together with treatment response at 3 months, overall survival, relapse-free survival and long-term toxicity data, were collated from referring centres. ResultsThe median follow-up was 78 months (range 2–301). Primary sites of disease included vagina (37), endometrium (29), vulva (16), ovary (7) and cervix (5). Eighty-six (91.5%) patients were treated with curative intent, eight (8.5%) were palliative treatments. Fifty patients received HDRB for recurrent disease, 39 patients for primary disease and five as part of adjuvant treatment. The anatomical site of disease treated with HDRB ranged from vagina (76), vulva (14) and peri-urethral sites (four). The 2- and 5-year local relapse-free survival rates were 76% and 72%, respectively; 15 patients experienced local failure only, whereas six patients had local and nodal/distant failure. The median time to local recurrence was 8 months (range 2–88 months). The 2- and 5-year overall survival rates for all patients were 67% and 47%, respectively; the median overall survival was 59 months. Seventy-nine (84%) patients had a complete response measured with imaging at 3 months. Grade 3 toxicity was reported in 14 patients (14.8%). ConclusionThis retrospective series suggests the use of interstitial brachytherapy for vulvovaginal gynaecological malignancy to be an effective and safe treatment option. Good local control was achieved with a tolerable toxicity profile; it is a valuable treatment modality.

Phase Ib Study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis (1243)

Phase Ib Study of intraperitoneal ipilimumab and nivolumab in patients with recurrent gynecologic malignancies with peritoneal carcinomatosis (1243)

Minimally invasive pelvic exenteration for gynaecological malignancies: the challenge of patients' selection.

Pelvic exenteration is a radical procedure representing a salvage option in patients with recurrent or persistent gynaecological malignancies. It can be performed with an open or minimally invasive approach. Different studies have demonstrated optimal peri-operative outcomes of minimally invasive pelvic exenteration with no survival difference when compared with an open approach. In this article, we discuss the importance and the challenge of patient selection for pelvic exenteration and more specifically for minimally invasive pelvic exenteration.

Balloon Trocar Is a Suitable Instrument for Retroperitoneal Para-aortic Lymphadenectomy in Gynecologic Malignant Diseases

To demonstrate the surgical technique of retroperitoneal para-aortic lymphadenectomy to prevent peritoneal rupture in gynecologic malignant disease. In this video, the authors describe how to use a balloon trocar to create a safe and efficient working space without peritoneal rupture. A step-by-step video demonstration of a surgical technique. Department of Gynecology and Obstetrics, Mie University, Tsu, Japan. Para-aortic lymphadenectomy is a part of most gynecologic oncology procedures for primary and recurrent gynecologic malignancies. There are 2 approaches to para-aortic lymphadenectomy: transperitoneal and retroperitoneal approaches. Although there are no significant differences between these approaches (such as in terms of the number of isolated lymph nodes or related complications), they are performed based on the operator's preference. The retroperitoneal approach is an unfamiliar surgical technique compared with usual laparotomy and laparoscopic surgery, and its disadvantages include a steeper learning curve for attaining proficiency. It is also difficult to develop the retroperitoneal space without a peritoneal rupture. In this video, we demonstrate the use of balloon trocars to create a retroperitoneal compartment. The patient was placed in the lithotomy position with the pelvis elevated at 5° to 10°. The left internal iliac approach, which is considered the standard approach, was used in this case (Fig 1). After identifying the left psoas muscles and the ureter crossing the common iliac artery, dissection of the left para-aortic lymph node was initiated (Supplemental Video 1, 2). Herein, we demonstrated a successful surgical technique for retroperitoneal para-aortic lymphadenectomy to prevent peritoneal ruptures.

R0 Resection in Recurrent Gynecologic Malignancy: Pelvic Exenteration and Beyond.

Pelvic exenteration is a radical surgery, but oftentimes, it is the last curative option for patients with recurrent gynecologic malignancies who have exhausted more conservative therapies. Mortality and morbidity outcomes have improved over time, but there are still significant peri-operative risks. Considerations before pursing pelvic exenteration must include the likelihood of oncologic cure and patients' fitness to undergo such a procedure, particularly given the high rate of surgical morbidity. Pelvic sidewall tumors have been a traditional contraindication for pelvic exenteration due to the difficulty in obtaining negative margins, but the use of laterally extended endopelvic resection and intra-operative radiation therapy allows for more radical resection of recurrent disease. We believe that these procedures to achieve R0 resection can expand the use of curative-intent surgery in recurrent gynecologic cancer, but require the surgical expertise of colleagues in orthopedic and vascular surgery and collaboration with plastic surgery for complex reconstruction and optimization of post-operative healing. Surgery of recurrent gynecologic cancer including pelvic exenteration, requires careful patient selection, pre-operative medical optimization and prehabilitation, and thorough counseling to optimize outcomes, both oncologic and peri-operative. We believe the creation of a well-developed team, including surgical teams and supportive care services, can lead to the best patient outcomes and improved professional satisfaction amongst providers.

Ocular toxicity and mitigation strategies for antibody drug conjugates in gynecologic oncology

Recently, two antibody drug conjugates were FDA approved for the treatment of recurrent gynecologic malignancies. Both of these new agents are associated with ocular toxicity. Ocular toxicity can be prevented and mitigated by utilizing recommended eye care strategies.

Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies.

We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. The median age of the patients was 56 years (range, 35-79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4-49.6). Reasons for first ICI discontinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4-10.4). The median overall survival was 21.3 months (range, 10.1-52.7). Neither patient who discontinued ICI treatment due to AEs experienced AE relapse during second ICI treatment. These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely support this practice.

569P Pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide for recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer: Real-life clinical experience

Single agent immune checkpoint inhibitors are largely ineffective in treating recurrent ovarian cancer (OC). In a recently completed phase 2 clinical trial at our institute (NCT02853318), we combined pembrolizumab with anti-VEGF bevacizumab and oral metronomic cyclophosphamide in patients with recurrent ovarian cancer. Our phase 2 trial had a median progression free survival (PFS) of 10.0 months and 25% of the recurrent OC patients had a PFS > 12 months with excellent quality of life. Based on the results of this trial, our center has been using this regimen off label in patients with recurrent gynecologic malignancies, given the limited efficacy of traditional second line chemotherapies in this patient population.

Negative effects of antibiotics and low BMI on overall survival of PD-1 inhibitors in patients with recurrent gynecologic malignancies (166)

<b>Objectives:</b> Antibiotic use or BMI has been reported to be associated with the effectiveness of ICI in solid tumors. We evaluated associations between antibiotic use either prior to ICI or during ICI, BMI at ICI initiation, and oncological outcomes. <b>Methods:</b> We examined patients with recurrent gynecologic malignancies who underwent PD-1 monotherapy at two academic institutions. Clinical data, including antibiotic use within 30 days of initiation of ICI or during ICI treatment, BMI, tumor site, chemotherapy-free interval, prior history of radiotherapy, the objective response at 12 weeks, PFS, and OS, were assessed. <b>Results:</b> A total of 204 patients were eligible, of whom 22.1% (45/204) and 41.2% (84/204) received antibiotics before and during ICI, respectively. Among the patients, 18.1% (37/204) were underweight. Based on tumor site, ovarian cancer was most common (51.0%, 104/204), followed by the cervix (24.5%, 50/204) and endometrial cancer (17.6%, 36/204). About 45.1% of patients had one or two previous lines of chemotherapy, and 80.4% (164/204) patients had chemotherapy-free intervals of less than six months. In terms of overall survival, endometrial cancer showed the best survivals among gynecologic malignancies (p = 0.034). In addition, low BMI, antibiotic use before or during ICI, and chemotherapy-free interval were associated with poor overall survival. In multivariate analyses, the negative association between low BMI (HR: 2.209; 95% CI: 1.236-3.949; p=0.007) and antibiotic use during ICI (HR: 1.910; 95% CI: 1.106-3.297; p=0.02) remained significant for OS. No significant association between objective response rates at 12 weeks and BMI or antibiotics use was observed. <b>Conclusions:</b> Antibiotics use during ICI, or low BMI were associated with reduced survival from ICI in recurrent gynecologic malignancies, which is in line with previous reports on non-gynecologic malignancies. Further research is needed to find a strategy to improve clinical outcomes with ICI in this population.

Colostomy for large bowel obstruction at the end of life: What do patients gain from palliative surgery? (598)

Colostomy for large bowel obstruction at the end of life: What do patients gain from palliative surgery? (598)

LIO-1: Initial phase 2 experience of lucitanib + nivolumab in patients with metastatic or recurrent cervical cancer (NCT04042116; ENGOT-GYN3/AGO/LIO) (034)

<b>Objectives:</b> Lucitanib is a potent, selective inhibitor of the tyrosine kinases VEGFR1-3, PDGFRα/ß, and FGFR1-3 that is being investigated in combination with the programmed cell death receptor 1 (PD-1) inhibitor nivolumab in four recurrent gynecologic malignancies (cervical, endometrial, ovarian, and ovarian/endometrial clear-cell cancers) in an ongoing phase II study, using a Simon's two-stage design. To maximize lucitanib exposure and potential clinical benefit of the combination, individualized lucitanib dose titration is utilized. We presented initial data from the cervical cancer cohort. <b>Methods:</b> Patients with metastatic or recurrent cervical cancer of squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma histology, who received ≥1 prior platinum-based chemotherapy regimen, with or without bevacizumab, were enrolled. Prior treatment with a PD-1 or programmed cell death ligand-1 (PD-L1) inhibitor was prohibited. All patients-initiated treatment with lucitanib 6 mg orally once daily (QD) + nivolumab 480 mg intravenously every 28 days. Lucitanib dose was escalated from 6 mg to 8 mg and up to 10 mg QD in patients who met safety-based titration criteria. Tumor response was assessed by investigators per RECIST v1.1. Data cut-off was September 1, 2021. <b>Results:</b> Twenty patients have been treated to date (median treatment duration: 85 days, range: 1-343+); 15 (75%) remain on treatment (13 remain on the combination and two on nivolumab monotherapy). Eleven (55%) patients received ≥2 prior anticancer regimens; nine (45%) had prior bevacizumab. To date, 17 (85%) patients have completed ≥1 cycle; two patients have escalated lucitanib to a dose of 8 mg, and three to the maximum dose of 10 mg. The most frequent anygrade treatment-emergent adverse events (TEAEs) have been hypertension (<i>n</i>=13, 65%), decreased appetite (<i>n</i>=11, 55%), asthenia/fatigue (<i>n</i>=10, 50%), and nausea (<i>n</i>=10, 50%). The most frequent grade ≥3 TEAE has been hypertension (<i>n</i>=4, 20%). Three (15%) patients discontinued lucitanib due to a related TEAE (colonic fistula, hypertension, and proteinuria). As of the data cut-off, 17 patients had at least one post-baseline tumor assessment, with four confirmed partial responses (PRs), eight patients with stable disease (7 remain ongoing), and five patients with the best response of progressive disease reported. The durations of PR range from 1.8+ to 9.3+ months. Of the four responding patients, three had received prior bevacizumab. <b>Conclusions:</b> Promising signs of antitumor activity in patients with metastatic or recurrent cervical cancer were noted in this initial analysis. Toxicity has been manageable and is consistent with that previously reported for lucitanib and nivolumab, and other agents of both classes. Having met Simon's two-stage stage I requirements (≥3 confirmed responses), study accrual continues in stage II of the cervical cancer cohort. Additional and more mature data, including biomarker analyses, will be presented at the meeting.

Laterally extended endopelvic resection for advanced or recurrent gynecological malignancies: clinicopathological analysis

To explore the feasibility and safety of laterally extended endopelvic resection (LEER) for advanced and recurrent gynecological malignancies with pelvic sidewall involvement and to evaluate this therapeutic potential of this novel salvage treatment. The clinicopathological data of 5 patients with gynecological malignancies who received laparoscopic LEER treatment in Obstetrics and Gynecology Hospital of Fudan University from January 2019 to September 2021 were retrospectively analyzed, including 3 cases of recurrent cervical cancer, 1 case of primary advanced endometrial cancer and 1 case of pelvic aggressive angiomyxoma. Among them, four patients achieved complete resection (R0) with a negative resection margin; the other patient with recurrent cervical cancer did not complete surgery because of the extreme risk of continuing surgery. The median operation time was 345 (225-482) minutes and the median blood loss was approximately 300 (200-600) ml. Complications occurred in three patients, including lymphocysts, urinary tract infections, and deep venous thrombosis of the lower extremities. Within a median follow-up time of 283 (128-715) days, 4 patients survived tumor-free, and 1 patient died. The high rate of complete resection (R0) and the encouraging oncological outcomes suggest that LEER may be an alternative treatment option for patients with advanced and recurrent gynecological malignancies involving the pelvic sidewall.

The impact of art therapy on anxiety and hope in patients with gynecologic cancer undergoing chemotherapy

Clinical research investigating the benefits of art therapy in individuals undergoing cancer treatment is growing, yet study designs focusing on certain cancers such as gynecologic malignancies are lacking. This study aimed to assess the impact of art therapy interventions on both anxiety and hope in patients with gynecologic cancer patients. The study design was prospective and non-randomized. Eligible patients had a primary or recurrent gynecologic malignancy, and were scheduled to receive at least six cycles of chemotherapy over eighteen weeks. Patients completed State Hope and State Anxiety questionnaires before and after each of five art therapy interventions during chemotherapy. Eighteen patients completed the study. Both anxiety and hope significantly improved after each art therapy session except for one. In addition, both anxiety and hope significantly improved between visit 1 and visit 5: State Hope -Visit 1 vs. Visit 5 (35.3 ± 7.8 vs. 40.0 ± 7.2), p = 0.019, effect size = 0.63; State Anxiety -Visit 1 vs. Visit 5 (32.8 ± 9.3 vs. 27.8 ± 8.8), p = 0.038, effect size = −0.53. The results showed art-based interventions facilitated by a board-certified art therapist positively impacted two domains in the quality of life of gynecologic cancer patients undergoing chemotherapy. The attitude of patients, namely, a willingness to accept art therapy, may influence the outcome of the interventions.

Radiofrequency and microwave ablation for treatment of recurrent gynecologic malignancies

ObjectiveRadiofrequency ablation and microwave ablation are used to vaporize tumors not amenable to surgical resection. We sought to evaluate the safety and efficacy of radiofrequency and microwave ablation for the...

CtDNA in treatment response monitoring in patients with relapsed gynecologic malignancies.

e17501 Background: The role of immunotherapy in gynecologic malignancies continues to evolve. Use of immune checkpoint blockade (ICB) agents have consistently demonstrated less than a 15% response rate in ovarian, cervical, and subsets of endometrial cancer. Given the limited number of responders, a novel approach to treatment monitoring is needed to better sequence therapies. Circulating tumor DNA (ctDNA) surveillance in patients treated with ICB is one such approach that has been shown to predict clinical benefit. We sought to evaluate this approach in patients with recurrent gynecologic malignancies managed with ICB therapy. Methods: In this retrospective analysis of real-world data, plasma samples (n = 208) from 28 patients with recurrent/metastatic ovarian (n = 8), endometrial (n = 14), and cervical (n = 6) cancers were identified as having received ICB therapy. A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for the detection of ctDNA in plasma samples. Serial time points were collected to monitor ctDNA levels in response to immunotherapy. Results: Response assessment results and longitudinal plasma samples were available for 19 patients. Pre-ICB plasma samples were available for 11 patients. Of these ctDNA was detected in 73% (8/11) of patients. All patients with progressive disease (10/10) had rising ctDNA levels that preceded radiological findings by a median of 2.8 months. One patient with rising ctDNA concentration presented with stable disease by imaging at the last follow-up. The remaining 8 patients demonstrated response to therapy that coincided with a declining or negative ctDNA level; 5 with partial response had a decline in ctDNA level prior to imaging (n = 3) or lack of ctDNA detection (n = 2), and 3 with complete response remained ctDNA negative, prior to imaging. Patients that exhibited a rise in ctDNA concentration (n = 11) (consecutive time points) while undergoing ICB therapy were associated with resistance to treatment (HR = 4.58 95%CI: 1.048-20.03, p = 0.04). TMB and MSI status (binary) were not predictive of response in univariate (p = 0.8, p = 0.9) analyses. Conclusions: ctDNA monitoring during the course of immunotherapy for relapsed gynecologic malignancies allows for accurate determination of therapeutic response and early prediction of disease progression. This enables timely assessment with imaging, and change in treatment plan. Our data suggest that patients with gynecologic malignancies may benefit from personalized, tumor-informed ctDNA testing to guide treatment decisions. Prospective studies are needed to establish the clinical utility of ctDNA monitoring in patients with gynecologic malignancies undergoing systemic therapies.

Efficacy and Safety of Recombinant Human Adenovirus Type 5 (H101) in Persistent, Recurrent, or Metastatic Gynecologic Malignancies: A Retrospective Study.

BackgroundTo assess the efficacy and safety of recombinant human adenovirus type 5 (H101) in patients with persistent, recurrent, or metastatic gynecologic malignancies.MethodsThe study retrospectively enrolled patients with persistent/recurrent/metastatic gynecologic malignancies who received H101-containing treatment at The First Affiliated Hospital of Xi’an Jiaotong University from September 1, 2019 to September 30, 2021. H101 was injected intratumorally into target lesions and dosage was calculated based on tumor diameter once a day for five consecutive days. The primary endpoint was local control (LC) rate. Secondary endpoints included objective response rate (ORR), duration of response (DOR) and progression-free survival (PFS). Safety was the exploratory endpoint. Depending on prior treatment, patients received H101 either as monotherapy or as a combination therapy.ResultsTotally, 29 patients were enrolled in the study. Median follow-up was 6.3 months (range: 3.2-27.9) from data analysis cut-off on December 31, 2021. The LC rate at 3 months was 44.8%, while ORR was 72.4%. Median DOR and PFS rates were not determined. The DOR rate, PFS rate at 6 and 12 months were 88.1%, 74.6% and 70.5%, 62.2%, respectively. Responses were observed in all four cancer types. Most treatment-related adverse events (90.5%) were grade 1 or 2, with the most common being fever (70%). Clinically significant adverse events were uncommon (7.9% in grade 3 and 1.6% in grade 4). No treatment-related deaths occurred.ConclusionOur study showed that H101 (either monotherapy or combination therapy) has promising efficacy and favorable safety in patients with persistent, recurrent, metastatic gynecologic malignancies.