Pre-operative opioid use is common and should be considered a comorbidity among surgical candidates. Our objective was to describe the rate of pre-operative opioid use and patterns of post-operative ...outpatient opioid prescribing in a cohort of gynecologic oncology patients.
A retrospective cohort study was conducted with 448 gynecologic oncology surgical patients undergoing surgery for a suspected or known cancer diagnosis from January 2016 to December 2016. Pre-operative opioid users (n=97) were identified. Patient and surgical characteristics were abstracted, as was post-operative opioid prescription (type of opioid, oral morphine equivalents amount) and length of stay. For pre-operative opioid users, the type of opioid prescribed post-operatively was compared with the type of pre-operative opioid. Pre-operative opioid users were compared with non-users, stratified by surgery type. Descriptive statistics were analyzed using χ
statistic, and medians were compared using a Mann-Whitney U statistic.
Pre-operative opioid prescriptions were noted in 21% of patients, and 24% of these had two or more opioid prescriptions before surgery. The majority of pre-operative opioid users (51%) were maintained on the same agent post-operatively at the time of discharge, but 36% were switched to a different opioid and 7% were prescribed an additional opioid. Overall and in laparotomies, pre-operative opioid users received higher volume post-operative prescriptions than non-users. There was no difference in post-operative prescription volume for minimally invasive surgeries or in length of stay between pre-operative users and non-users.
Pre-operative opioid use is common in gynecologic oncology patients and should be considered during pre-operative planning. Pre-operative opioid use was associated with a higher volume and wider range of post-operative prescription. Over 40% of opioid users were discharged with either an additional opioid or a new opioid, highlighting a potential missed opportunity to optimize opioid safety. Further research is needed to characterize the relationship between pre-operative opioid use and peri-operative outcomes and to develop strategies to manage pain effectively in this population without compromising opioid safety.
BackgroundPatients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) have a significant need for effective treatment options. Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific ...antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/major histocompatibility complex interaction. Phase I results in patients with R/R B-NHL demonstrated that odronextamab monotherapy could achieve deep and durable responses with a generally manageable safety profile (ELM-1; NCT02290951). As part of a biomarker analysis of the same study, we investigated potential biomarkers and mechanisms of resistance to odronextamab.MethodsPatients with R/R B-NHL enrolled in ELM-1 received one time per week doses of intravenous odronextamab for 4×21 day cycles, then doses every 2 weeks thereafter. Patient tumor biopsies were obtained at baseline, on-treatment, and at progression. Immune cell markers were analyzed by immunohistochemistry, flow cytometry, single-cell RNA sequencing, and whole genome sequencing.ResultsBaseline tumor biopsies showed that almost all patients had high proportions of B cells that expressed the CD20 target antigen, whereas expression of other B-cell surface antigens (CD19, CD22, CD79b) was more variable. Responses to odronextamab in patients with diffuse large B-cell lymphoma were not related to the relative level of baseline CD20 expression, cell of origin, or high-risk molecular subtype. A potential link was observed between greater tumor programmed cell death-ligand 1 expression and increased likelihood of response to odronextamab. Similarly, a trend was observed between clinical response and increased levels of CD8 T cells and regulatory T cells at baseline. We also identified an on-treatment pharmacodynamic shift in intratumoral immune cell subsets. Finally, loss of CD20 expression through inactivating gene mutations was identified as a potential mechanism of resistance in patients who were treated with odronextamab until progression, as highlighted in two detailed patient cases reported here.ConclusionsThis biomarker analysis expands on clinical findings of odronextamab in patients with R/R B-NHL, providing verification of the suitability of CD20 as a therapeutic target, as well as evidence for potential mechanisms of action and resistance.
Odronextamab is a fully‐human IgG4‐based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T‐cell‐mediated cytotoxicity independent of T‐cell‐receptor ...recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first‐in‐human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B‐cell non‐Hodgkin lymphoma (B‐NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half‐maximal effective concentration values from in vitro cytokine release assays (range: 0.05–0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1–10 mg/L) were useful to predict efficacious concentrations in patients and inform dose‐escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step‐up dosing, the highest‐tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step‐up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B‐NHL.
Sexual dysfunction can be a long-term issue for women with gynecologic cancer. This study assesses the extent of sexual and marital dysfunction women face following treatment of a gynecologic cancer.
...A cross-sectional study of women with gynecologic cancer was conducted using a 181-item survey. Sexual dysfunction was measured by change in the Female Sexual Function Index score; marital dysfunction was measured by change in Intimate Bond Measure from prediagnosis to posttreatment. Paired t tests and Fisher exact test were used to compare women with dysfunction to those without dysfunction.
Three hundred twenty women were enrolled (mean age, 56.0 SD, 12.0 years). Among all women, sexual function declined from a score of 21.3 (SD, 10.4) prior to 15.3 (SD, 10.2) (P < 0.001), and sexual activity decreased from 6.1 (SD, 6.8) to 2.6 (SD, 4.9) times per month following treatment (P < 0.001). Among the 208 women who were sexually active at the time of study, sexual dysfunction after treatment was associated with younger age (50.9 SD, 11.7 years to 57.3 SD, 12.3 years), ovarian (40.7% vs 30.7%) or cervical (21.0% vs 10.2%) cancer diagnosis, chemotherapy treatment (72.8% vs 50.4%), and being in a relationship (97.3% vs 82.7%). Among women in relationships, 27% experienced marital dysfunction.
Women who are younger, have an ovarian or cervical cancer diagnosis, receive chemotherapy, or are in a committed relationship are at particularly high risk of sexual dysfunction. These women should be provided information about the risks associated with their cancer treatment.
The Fertility Attitudes and Cancer Treatment Study (FACTS) aims at better understanding the reasons and priorities of young adult cancer patients making decisions for fertility preservation (FP). ...Identifying the factors that center around a patient's fertility decisions will support the development of educational tools for providers and improve clinical care to meet patients' reproductive needs.
An exploratory qualitative study was conducted of 27 newly diagnosed male and female cancer patients who had presented for an oncofertility consultation. Interviews lasted ∼30 minutes and were transcribed verbatim. A thematic analysis was conducted to explore the factors driving decisions for future fertility. Themes were grouped to address the following topics: reasons for/against FP, patient priorities, informational needs, support, wellness, and satisfaction with information. Strength of the theme was determined by examining the frequency of a response.
Patients who chose FP versus those who did not choose FP and men versus women proved to be more similar than different in their reasoning, priorities, and informational needs for FP decisions. Patients who chose FP identified a "concern for future fertility" as a top reason to do so and "parenthood" as a top priority. For those who did not choose FP, "cancer treatment" was identified as their top priority. For patients identifying financial barriers, 50% of them were able to overcome this to pursue FP.
Reproductive-aged patients diagnosed with a new cancer should be referred to a reproductive specialist and provided the opportunity to come to a fertility decision on their own before initiating cancer treatment.
The Fertility Attitudes and Cancer Treatment Study (FACTS) is a two-phase research initiative aimed to understand factors involved with decision making for future fertility. The FACTS will improve ...services and utilization of fertility preservation (FP) before cancer treatment. Phase-I examined patient characteristics as associated with FP decision.
A retrospective cohort study of 108 reproductive-aged (18-45 years) males and females who received a fertility consultation before cancer treatment from January 1, 2012 to April 30, 2014 was conducted. Chi-square, student's t-test, and logistic regression were conducted to examine associations with FP decision.
The utilization rate of FP following fertility consultation was 49%. Gender was the most significant factor contributing to FP decision; 74% of those who choose FP were male (odds ratio = 12.5; 95% confidence interval 5.1-31.4). Those who opted for FP were more likely to be Caucasian (p = 0.042), have a solid tumor (p = 0.03), and have a shorter time from diagnosis to fertility consultation (29.5 vs. 58.8 days; p = 0.017). Age, relationship, tumor location, treatment plan, and parity were not significant predictors of FP.
Current perceptions about patient demographics do not predict FP utilization by young adult cancer patients. Providing patients an informed fertility consultation has demonstrated an increase in FP utilization to nearly one-half of patients. Despite gender being a significant factor in choosing FP, the study did not provide reasons as to why. The phase-II study will explore patients' reasons for FP decision in a qualitative design to understand these differences.
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Background: Women report distress over relationships, body image and sexual function after cancer; those < 50 have a 3-times greater risk of sexual dysfunction following ...treatment. Survivors desire integrated and multifaceted interventions to maintain optimal sexual health. Methods: We employed a mixed-method (concurrent nested) design to identify women’s need for sexual health support after diagnosis. Women 18-50 years old were recruited at a national conference for young survivors and local breast/gynecologic clinics. Qualitative and quantitative assessments identified sexual health factors and support needs most prevalent. Summary statistics and theme analysis using grounded theory was conducted. Results: Participants included 128 women (mean diagnosis age 35.6) and were: married (71%), breast cancer (46%), mastectomy (40%), hysterectomy (30%), chemotherapy (81%), radiation (51%) and completed treatment (67%). Nearly 1/3 of women reported their relationship worsening, 97% contribute it to less sexual activity; 71% were unsatisfied with their sexual relationship compared to before diagnosis. Women (77%) feel their oncologist should discuss sexual health and 74% prefer information prior to treatment. When asked to identify resources 82% desired helpful products/strategies; other desired resources include: written education (65%), medications/lubricants (68%), personal counseling (37%), sex therapist (41%) and local/web-based support groups (36%). When asked to describe their experience with sexual health women reported the following themes: supportive partners, sexual health status, guilt, stolen identity, loss of desire, isolation, treatment side effects, menopause, vaginal changes, maintaining relationships, coping mechanisms, fertility, self-image, grief, intimacy, and desire for oncologist support. Conclusions: Sexual health support after diagnosis is an unmet need that can be integrated into treatment to greatly improve the quality of life for survivors. Women desire their oncologist to provide information before treatment and through survivorship on products/strategies, education, and medications/lubricants to maintain sexual function. Young women do not desire social support resources.
Introduction: This study aims to assess the role of route of hysterectomy, operative times, and lymphadenectomy on sexual function using the female sexual function index (FSFI) questionnaire. ...Methods/materials: The FSFI, a survey of validated instruments, was used to assess sexual dysfunction in 171 women with gynecologic cancer in this cross-sectional study. A sub-analysis was performed for patients who underwent hysterectomy. A significant decline in sexual function was determined to be a decrease of 5.8 points from pre-diagnosis to post-treatment scores using a Reliable Change Index Statistic. Statistical analysis included chi-square, Student's t-tests, and logistic regression. The primary outcome was determination if surgical route is associated with sexual dysfunction. Secondary outcomes were effect of operative time, lymphadenectomy, and lymph nodes removed on postoperative sexual function. Results: Hysterectomy was performed in 123 patients; 67% (n = 82) had total abdominal hysterectomy (TAH) and 33% (n = 41) had minimally invasive surgery (MIS). Women with TAH reported greater sexual dysfunction (50% vs. 22%; OR: 3.6; 95% CI 1.5-8.4), were more likely to be age < 50 (36.6% vs. 14.6%; OR: 3.4; 95% CI 1.3-8.9), have longer operating times (270 min ± 108 vs. 230 min ± 49; p = 0.02), and have more lymph nodes removed (15.9 ± 6.2 vs. 12.2 ± 9.8; p = 0.05). In logistic regression, TAH and age < 50 were independent predictors of sexual dysfunction, while operative time and lymphadenectomy were not. Conclusions: TAH and age < 50 are risk factors for sexual dysfunction following hysterectomy for gynecologic cancer.
TPS7093 Background: Approximately 30–40% of patients (pts) with high-risk, aggressive B-NHL are refractory to or relapse after first-line chemoimmunotherapy. Although autologous stem cell ...transplantation (ASCT) and chimeric antigen receptor (CAR) T-cell therapies are available in the second line, access, eligibility, tolerability, and cost pose limitations for pts, and there remains a need for well-tolerated, effective off-the-shelf therapies in this setting. Odronextamab, a CD20×CD3 bispecific antibody, demonstrated encouraging clinical activity (complete response CR rate 31.5%; median duration of CR 17.9 months) and a generally manageable safety profile as monotherapy in pts with heavily pretreated R/R diffuse large B-cell lymphoma (DLBCL) in the Phase 2 ELM-2 study (Ayyappan, et al. ASH 2023). This study will evaluate odronextamab versus SOC treatment in pts with DLBCL who have relapsed early (within 1 year) or were refractory to first-line therapy. Methods: OLYMPIA-4 (EudraCT 2022-502783-21-00) is a Phase 3, randomized, open-label, multicenter study of odronextamab versus SOC in pts with previously treated aggressive B-NHL. Odronextamab will be administered intravenously in 21-day cycles, with step-up dosing during Cycle (C) 1 to mitigate the risk of cytokine release syndrome, at 160 mg on Days 1, 8, and 15 of C2–4, then as maintenance at 320 mg Q2W until one year from the start of treatment, progressive disease, or death. Treatment in the SOC arm consists of physician’s choice of salvage therapy with intent to proceed to ASCT. SOC regimens are: ifosfamide, carboplatin, and etoposide (ICE); dexamethasone, cisplatin, and cytarabine (DHAP); or gemcitabine, dexamethasone, and cisplatin (GDP), ± rituximab. Pts will receive up to three 21-day cycles of salvage therapy, followed by ASCT. Pts without an optimal response to salvage therapy or ASCT may cross over to receive one year of odronextamab treatment. Key inclusion criteria: ≥18 years of age; aggressive B-NHL that is primary refractory or relapsed within one year of first-line treatment initiation; intent to proceed to ASCT; measurable disease; ECOG performance status 0–1; and adequate organ and hematologic function. Pts with central nervous system lymphoma or active infection are excluded. The primary endpoint is event-free survival, as assessed by independent central review. Key secondary endpoints are progression-free survival, best overall response, and change from baseline in physical function, as measured by EORTC QLQ-C30. Other secondary endpoints include CR rate, duration of response, overall survival, minimal residual disease, pharmacokinetics, and incidence and severity of treatment-emergent adverse events. The trial is currently recruiting and is expected to enroll ~216 pts at ~200 global sites. Clinical trial information: 2022-502783-21-00.
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