BackgroundEftilagimod alpha (efti; IMP321) is a soluble LAG-3 protein (LAG-3Ig) that binds to a subset of MHC class II molecules and mediates activation of antigen-presenting cells followed by CD8 ...T-cells. Weekly paclitaxel is a standard of care chemo-regimen after failure of endocrine-based therapy for metastatic breast carcinoma (MBC). AIPAC (Active Immunotherapy PAClitaxel) investigated the addition of efti to weekly paclitaxel in these patients (pts).MethodsThis placebo-controlled, double-blinded, 1:1 randomized phase IIb trial enrolled pts with measurable disease, HR+ HER2- MBC after endocrine-based therapy. Pts received paclitaxel (80 mg/m² IV on D1, D8, D15) + efti (30 mg) or placebo on D2, D16 (every 2 weeks) for up to 24 weeks following efti/placebo for up to 52 weeks. The primary endpoint (EP) was progression-free survival (RECIST1.1) by BICR. Secondary EPs included overall survival (OS), PFS (local read), overall response rate (ORR), biomarker, quality of life. Exploratory EPs included univariate/multivariate analyses.Results227 pts were randomized (Jan2017-Jul2019). All except 1 received ≥1 treatment and were included in the full analysis set efti (n=114); placebo (n=112). Data cut-off was 14May2021 (min. follow-up= 22 months). Median age was 60 yrs with ECOG 0 in 61.5%. 91.6% had visceral disease. Pts were mostly endocrine resistant (84%) and partially pre-treated with CDK4/6 inhibitors (44.2%). Post-study treatment was similar. Median OS was 20.4 (95% CI: 14.3-25.1) months in the efti group vs. 17.5 (95% CI: 12.9-21.9) in the placebo group. HR was 0.88 (95%CI: 0.64-1.19; p=0.197). In predefined univariate analyses, younger pts, low baseline monocytes and luminal B showed significant/clinically meaningful improvement in OS (table 1).Efti increased PBMC/T cell (CD4/CD8) count vs. placebo, correlating with improved OS (Spearman Rho=0.6, p=0.02 for CD8 T cells). In a whole population multivariate cox regression model, increasing BMI and prior treatment with CDK4/6 were independent significant poor prognostic markers for PFS and OS.TEAEs leading to discontinuation were similar at 5.3%(efti) & 6.3%(placebo). PFS (Primary EP) and safety were reported at SABCS 2020 (Abstract#132).Abstract 948 Table 1Overall survival by subgroups at final analysisConclusionsEfti added to paclitaxel led to a non-significant 2.9 months median OS increase in HR+ HER2- MBC pts after endocrine-based therapy. Effects were significant in pts <65yrs, with low monocytes and more aggressive disease (luminal B). Efti increased circulating CD4/CD8 T cells, which significantly correlated to improved OS. Weekly paclitaxel + efti should be further investigated in MBC.Trial RegistrationThe trial identifiers are IMP321-P011 (code for sponsor), 2015-002541-63 (EudraCT) and NCT02614833 (ClinicalTrials.gov).Ethics ApprovalThe study was approved by relevant ethic committees and institutional review boards.
Primary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly in elderly women. The diagnosis is based on histology and immunohistochemistry of a biopsy. Given the rarity of ...vaginal melanoma, no standardized treatment guidelines are established; however, surgery is the primary treatment modality in the absence of metastatic disease. Most reports in the literature are retrospective single cases, case series, and population-based studies. The open surgical approach is the main modality reported. Here, we report for the first time a 10-step combined robotic-vaginal technique, with
resection of the uterus and total vagina, for treating clinically early-stage primary vaginal melanoma. In addition, the patient in our case underwent a robotic pelvic bilateral sentinel lymph node dissection. The literature on the surgical approach for vaginal melanoma is reviewed.
A 73-year-old woman was referred to our tertiary cancer center and was clinically staged according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging for vaginal cancer as FIGO-stage I (cT1bN0M0) and according to the American Joint Committee on Cancer (AJCC) for (cutaneous) Melanoma Staging as clinical stage IB. Preoperative imaging with magnetic resonance imaging, FDG-positron emission tomography-computed tomography, and ultrasound of the groins did not reveal any adenopathy nor metastases. The patient was planned for a combined vaginal and robotic
total vaginectomy and hysterectomy, as well as a pelvic bilateral sentinel lymph node dissection.
The surgical procedure was performed in 10 steps described in this case report. The pathology revealed free surgical margins and negative test results for all sentinel lymph nodes. The postoperative recovery process was uneventful, and the patient was discharged on day 5.
The main surgical approach reported for primary early-stage vaginal melanoma is open surgery. A minimally invasive surgical approach, described here as a combined vaginal-robotic
total vaginectomy and hysterectomy, for the surgical treatment of early-stage vaginal melanoma enables precise dissection, low surgical morbidity, and fast recovery for the patient.
Objective
Discrepancies exist among international guidelines on the surgical staging of para-aortic lymph nodes in locally advanced cervical cancer (LACC), varying from considering a para-aortic ...lymph node dissection, at least up to the inferior mesenteric artery, to a complete para-aortic lymph node dissection. In this study, we aim to assess the reproducibility of our recently reported robotic technique using indocyanine green for identifying besides primary pelvic sentinel lymph nodes (SLNs), secondary para-aortic SLNs in a first case-cohort of cervical cancer patients.
Methods
A retrospective case series of LACC patients with/without suspicious pelvic lymph nodes (LNs) on imaging (including two patients with an additional suspicious para-aortic LN) is reported. All patients underwent a robotic pelvic SLN and para-aortic sentinel/nonsentinel LN dissection using the da Vinci Xi platform. Indocyanine green was used as a fluorescent tracer, at a concentration of 1.9 mg/mL, and injected as 0.5 mL in each quadrant of the cervix.
Results
In a total of 10 cases, primary pelvic SLNs (90% bilateral) with subsequent secondary para-aortic SLNs were identified in all cases. Lower para-aortic SLNs were present in all cases, and upper para-aortic SLNs were found in 9 out of 10 cases. The mean age of the cervical cancer patients was 49.8 years (SD ± 6.89), and the mean body mass index (BMI; kg/m
2
) was 23.96 (SD ± 4.60). The median total operative time was 105.5 min (range: 89–141 min). The mean numbers of primary pelvic SLNs and secondary lower and upper para-aortic SLNs were 3.10 (SD ± 1.10), 2.90 (SD ± 0.74), and 2.30 (SD ± 1.57), respectively. The median number of total para-aortic LNs (PALNs) dissected per patient was 11.5. Six patients had positive primary pelvic SLNs, and two had secondary positive para-aortic SLNs. The nonsentinel para-aortic LNs were negative in all cases. There were no intra- or postoperative complications.
Conclusion
Our preliminary experience demonstrates the reproducibility of identifying, besides primary pelvic SLNs, secondary lower and upper para-aortic SLNs during robotic staging in LACC. A surgical approach limiting a complete para-aortic LN dissection could reduce the potential risks and morbidity associated with this procedure. To determine the sensitivity and negative predictive value of this new surgical approach, and whether the lower para-aortic SLNs under the inferior mesenteric artery are representative of the whole para-aortic region, large prospective observational studies are needed in LACC and/or those with suspicious pelvic LNs but apparent normal para-aortic LNs on imaging.
Background: Patients with persistent or recurrent cervical cancer, following primary treatment with concurrent chemoradiation, represent a subgroup eligible for pelvic exenteration. In light of the ...substantial morbidity associated with open pelvic exenterations, minimally invasive surgical techniques have been introduced. This systematic review aims to analyze and discuss the current literature on robotic-assisted pelvic exenterations in cervical cancer. In addition, novel aspects of compartment-based magnetic resonance imaging (MRI) are highlighted. Methods: This systematic review followed the PRISMA guidelines, and a comprehensive literature search on robotic-assisted pelvic exenterations in cervical cancer was conducted to assess, as main objectives, early and late postoperative complications as well as oncological outcomes. Inclusion and exclusion criteria were applied to select eligible studies. Results: Among the reported cases of robotic-assisted pelvic exenterations in cervical cancer, 79.4% are anterior pelvic exenterations. Intraoperative complications are minimal and early/late major complications averaged between 30–35%, which is lower compared to open pelvic exenterations. Oncological outcomes are similar between robotic and open pelvic exenterations. Sensitivity for locoregional invasion increases up to 93% for compartment-based MRI in colorectal cancer. A refined delineation of the seven pelvic compartments for cervical cancer is proposed here. Conclusions: Robotic-assisted pelvic exenterations have demonstrated feasibility and safety, with reduced rates of major complications compared to open surgery, while maintaining surgical efficiency and oncological outcomes. Compartment-based MRI holds promise for standardizing the selection and categorization of pelvic exenteration procedures.
During the last decade several case series have been published on robotic surgery in early and advanced stage ovarian cancer. Although most studies lack a significant oncological follow-up, more ...importantly criteria for patient selection for both robotic surgical staging (R-SS) and robotic interval debulking surgery (R-IDS) are not well defined. The objective of this study was to assess the surgical and oncological outcomes, using well-defined selection criteria, between robotic and open surgery in early and advanced stage ovarian cancer.
Single-center retrospective case cohort study including 96 ovarian cancer patients. For early stage ovarian cancer, patients were selected for R-SS after laparoscopic salpingo-oophorectomy of a suspicious adnexal mass. For advanced stage ovarian cancer, only patients receiving neoadjuvant chemotherapy and IDS were included in the study. Exclusion criteria were the presence of residual peritoneal disease after NACT and/or patients requiring additional complex surgical procedures.
For early stage ovarian cancer, similar median operative times were seen between R-SS and open surgical staging (O-SS), 132 min and 120 min respectively. Pelvic/para-aortic lymph node yield was similar between R-SS and O-SS, 22/11 nodes and 18/8 nodes respectively. Surgical upstaging occurred in 11.5% in the R-SS group and in 27.6% in the O-SS group. In advanced stage ovarian cancer, the BMI was significantly higher in the R-IDS group compared to the O-IDS group (27.8 vs 23.5; p =.006). The median follow was 52 months in the R-IDS group and 31 months in the O-IDS group. Recurrent disease occurred in 42.9% of the R-IDS group and in 45% of the O-IDS group. The length of hospitalization was significantly longer in the O-SS and O-IDS group (p <.00001).
Patients with clinically early stage ovarian cancer, confirmed after laparoscopic removal of a suspicious adnexal mass, are candidates for R-SS whilst maintaining similar surgical and oncological outcome measures as O-SS. In advanced ovarian cancer, suitable candidates for R-IDS are those who receive NACT with good response and no residual peritoneal disease, especially in patients with a high BMI, but large prospective randomized trials with well-defined criteria are needed.
Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue ...factor-directed antibody–drug conjugate, in this patient population.
This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396.
102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1–13·0). The confirmed objective response rate was 24% (95% CI 16–33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 38% of 101 patients), epistaxis (30 30%), nausea (27 27%), conjunctivitis (26 26%), fatigue (26 26%), and dry eye (23 23%). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three 3% patients), fatigue (two 2%), ulcerative keratitis (two 2%), and peripheral neuropathies (two 2% each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two 2% patients) and pyrexia (two 2%). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes.
Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer.
Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups.
Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a ...poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.
This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control.
Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio HR, 0.71 95% CI, 0.57 to 0.89;
= .003) and durvalumab + olaparib arms (HR, 0.55 95% CI, 0.43 to 0.69;
< .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR durvalumab
control, 0.42 95% CI, 0.22 to 0.80; HR durvalumab + olaparib
control, 0.41 95% CI, 0.21 to 0.75) and pMMR subgroups (HR durvalumab
control, 0.77 95% CI, 0.60 to 0.97; HR durvalumab + olaparib
control 0.57; 95% CI, 0.44 to 0.73); and in PD-L1-positive subgroups (HR durvalumab
control, 0.63 95% CI, 0.48 to 0.83; HR durvalumab + olaparib
control, 0.42 95% CI, 0.31 to 0.57). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab
control: HR, 0.77 95% CI, 0.56 to 1.07;
= .120; durvalumab + olaparib
control: HR, 0.59 95% CI, 0.42 to 0.83;
= .003). The safety profiles of the experimental arms were generally consistent with individual agents.
Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.
Abstract
Leiomyosarcomas of the uterine cervix are rare, mostly occurring in perimenopausal women. Diagnosis is based on pathology and immunohistochemistry. Surgery with a total abdominal ...hysterectomy and bilateral salpingo-oophorectomy remains the standard. A female patient in her 60s presented with heavy postmenopausal bleeding. Vaginal ultrasound scan and magnetic resonance imaging showed a large strongly vascularized cervical mass with features suspicious of sarcomatous degeneration. Positron Emission Tomography-Computed Tomography (PET-CT) did not reveal any evidence of metastases nor lymphadenopathy, but presence of right hydronephrosis. An abdominal hysterectomy with bilateral salpingo-oophorectomy, and end-to-end anastomosis of the right ureter, was performed. Pathology showed an International Federation of Gynecology and Obstetrics (FIGO)-stage 1B leiomyosarcoma of the uterine cervix. No adjuvant treatment was given. Adjuvant radiotherapy reduces the risk of recurrence but no survival impact. The benefit of adjuvant chemotherapy is questionable given the lack of randomized trials. Multidisciplinary research concerning molecular alterations of the disease is required to determine optimal management strategies with potential novel molecular therapies.
We report bone scan changes in 3 patients receiving aromatase inhibitors as adjuvant treatment for postmenopausal hormone receptor-positive breast cancer. Compared with bone scans before treatment, ...repeated scans after at least 10 months of aromatase inhibitor treatment showed increased activity in the peripheral skeleton and the skull. In 2 patients, these alterations could be correlated with increased markers of bone turnover. They probably result from high bone turnover induced by estrogen depletion caused by aromatase inhibitors. This effect should be taken into account in the differential diagnosis of a bone scan pattern suggestive of hyperparathyroidism, which was ruled out.
IntroductionPrimary vaginal melanoma is extremely rare, has a poor prognosis, and occurs mostly in elderly women. The diagnosis is based on histology and immunohistochemistry of a biopsy. Given the ...rarity of vaginal melanoma, no standardized treatment guidelines are established; however, surgery is the primary treatment modality in the absence of metastatic disease. Most reports in the literature are retrospective single cases, case series, and population-based studies. The open surgical approach is the main modality reported. Here, we report for the first time a 10-step combined robotic-vaginal technique, with en bloc resection of the uterus and total vagina, for treating clinically early-stage primary vaginal melanoma. In addition, the patient in our case underwent a robotic pelvic bilateral sentinel lymph node dissection. The literature on the surgical approach for vaginal melanoma is reviewed. Case presentationA 73-year-old woman was referred to our tertiary cancer center and was clinically staged according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging for vaginal cancer as FIGO-stage I (cT1bN0M0) and according to the American Joint Committee on Cancer (AJCC) for (cutaneous) Melanoma Staging as clinical stage IB. Preoperative imaging with magnetic resonance imaging, FDG-positron emission tomography-computed tomography, and ultrasound of the groins did not reveal any adenopathy nor metastases. The patient was planned for a combined vaginal and robotic en bloc total vaginectomy and hysterectomy, as well as a pelvic bilateral sentinel lymph node dissection. ResultsThe surgical procedure was performed in 10 steps described in this case report. The pathology revealed free surgical margins and negative test results for all sentinel lymph nodes. The postoperative recovery process was uneventful, and the patient was discharged on day 5. ConclusionThe main surgical approach reported for primary early-stage vaginal melanoma is open surgery. A minimally invasive surgical approach, described here as a combined vaginal-robotic en bloc total vaginectomy and hysterectomy, for the surgical treatment of early-stage vaginal melanoma enables precise dissection, low surgical morbidity, and fast recovery for the patient.
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