Objective. Platinum-resistant epithelial ovarian cancer (EOC), recurrent endometrial cancer (EC), and triple negative breast cancer (TNBC) are difficult to treat after failing standard therapies. This phase I study evaluated mirvetuximab soravtansine (MIRV) and gemcitabine in patients with recurrent FR alpha-positive EOC, EC, or TNBC to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) (primary endpoint). Methods. FR alpha-positive patients with platinum-resistant EOC, EC, or TNBC with <= 4 prior chemotherapy regimens (2 for EC) were enrolled. FR alpha expression requirement varied among eligible tumors and changed during the study. Results. Twenty patients were enrolled; 17 were evaluable for DLT. Half the patients received >= 3 prior chemotherapy lines. Most EOC and EC patients (78%) were medium (50-74%) or high(75-100%) FR alpha expressors. TNBC patients were low (25-49%) FR alpha expressors. The MTD/RP2D was MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days (Dose Level [DL] 3), where 5/7 patients demonstrated a partial response (PR) as their best response, including 2 confirmed ovarian responses whose time-to-progression and duration of response were 7.9/5.4 and 8.0/5.7 months respectively. Most common treatment-related adverse events at MTD were anemia and neutropenia (3/7 each, 43%), diarrhea, hypophosphatemia, thrombocytopenia, and leukopenia (2/7 each, 29%). DLTs were thrombocytopenia (DL1), oral mucositis (DL4) and diarrhea (DL4). Nine of 20 patients (45%; 95% CI: 21.1-68.9%) achieved PR as their best response, with 3/20 patients or 15% (95%CI, 0-32.1%) confirmed PR. Conclusion. MIRV and gemcitabine demonstrate promising activity in platinum resistant EOC at RP2D, but frequent hematologic toxicities.

e17577 Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy improves survival in ovarian cancer patients. Currently, no biomarkers exist to select for patients who best benefit from HIPEC. We compared the slicing landscape of ovarian cancer tumors of good and poor HIPEC responders in a Phase I clinical trial, to identify potential predictive biomarkers. Methods: A total of 35 ovarian cancer patients enrolled in a Phase I HIPEC trial (NCT01970722), in which nine patients had paired pre-and post treatment tissue samples collected. Pre-HIPEC tumor samples had RNA isolated, and whole-transcriptome library construction performed. FASTQ files from tumor samples were aligned to GRCH38 and ran through SplAdder (PMID:26873928) to identify alternative splicing events. Outlier splice events were ranked by mean log-likelihood score and converted to amino acid sequences using Bisbee (PMID:34031440). The top 15 outlier events were run through NetMHCpan (PMID:32406916) and DeepHLApan (PMID:31736974) to predict putative neoantigens. Results: Among nine HIPEC-treated ovarian cancer patients with available RNAseq data, five were considered good responders (≥12months PFS), and four as poor responders (<12 months PFS). Alternative splicing analysis identified 519splice events as outliers between good and poor responders, with 250reported to be novel. Of the 250 novel splicing events, we identified a novel protein coding 3’ end splice event in CPNE1 which was alternatively spliced in at a Percent-Spliced-In (PSI) of 99% in three out four poor responders. The same splice event was alternatively spliced at a PSI of 30.3% in four out of five good responders. CPNE1 plays a role in calcium mediated intracellular processes, and is involved in the TNF-alpha receptor signaling pathway, thus playing an important role in cell proliferation, differentiation, apoptosis, and modulation of immune responses and induction of inflammation. The encoded novel peptide from the CPNE1 splice event produced six predicted strong binding sites based on a binding score>0.80 and an immunogenic score>0.80. Conclusions: CPNE1 was identified as a differentially spliced event in poor HIPEC responders with ovarian cancer. Poor HIPEC responders had higher immunogenic score. Alternative splicing analysis may be a promising method to determine potential biomarkers for HIPEC treatment in ovarian cancer patients. Clinical trial information: NCT01970722 .

Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin confers a survival benefit in epithelial ovarian cancer (EOC) but is associated with renal toxicity. Sodium thiosulfate (ST) is used for nephroprotection for HIPEC with cisplatin, but standard HIPEC practices vary. A prospective, nonrandomized, clinical trial evaluated safety outcomes of HIPEC with cisplatin 75 mg/m2 during cytoreductive surgery (CRS) in patients with EOC (n = 34) and endometrial cancer (n = 6). Twenty-one patients received no ST (nST), and 19 received ST. Adverse events (AEs) were reported according to CTCAE v.5.0. Serum creatinine (Cr) was collected preoperatively and postoperatively (Days 5–8). Progression-free survival (PFS) was followed. Normal peritoneum was biopsied before and after HIPEC for whole transcriptomic sequencing to identify RNAseq signatures correlating with AEs. Forty patients had HIPEC at the time of interval or secondary CRS. Renal toxicities in the nST group were 33

EP266/#300 Figure 1 Abstracts A158 Int J Gynecol Cancer 2022;32(Suppl 3):A1–A274 on S etem er 3, 2023 by gest. P rocted by coright. http/ijgc.bm jcom / nt J G ynecol C acer: frst pulished as 10.11362022-igcs.356 on 4 D ecem er 222. D ow nladed fom

Objectives Compare nodal yield by minimally-invasive surgical approach in early-stage (I-II) ovarian cancer. Methods The National Cancer Database (NCDB) was queried for patients with early stage (I-II) ovarian cancer between 2004 and 2017 who underwent minimally-invasive staging to compare adequate nodal yield by surgical approach. Results A total of 93,605 early-stage ovarian cancer cases were identified: 49,169 (52.5%) were stage I and 18,747 (20.0%) were stage II. Data was evaluable for 36,440 cases (38.9%). 12.4% (4,529) of lymph node assessments were performed robotically, 17.7% (6,434) were performed laparoscopically, and 69.9% (25,477) were performed via laparotomy. Conversion rates were 0.7% from robotic to open and 3.4% from laparoscopic to open. The most common histologic type was non-epithelial ovarian cancer (67.8%, 24,695). 57.2% of cases reviewed were privately insured, 43.1% received care at academic programs. The odds of sampling more than 10 lymph nodes with a laparoscopic approach was 76% that of open approach [OR 0.758 (95% CI 0.712–0.807), p<0.001] but similar between robotic and open [OR 1.062 (95% CI 0.991–1.138), p=0.091]. Robotic approach was associated with a higher median number of lymph nodes (median: robotic = 8, open = 7, laparoscopic = 4, all p<0.001). Open and robotic approaches were associated with higher LN yield (p<0.001), as was private insurance (p<0.001) figure 1. Nodal yield by surgery Robotic approach leads to a higher yield of pelvic lymph nodes (8) as compared to laparoscopic (4) and open (7). Conclusions Robotic-assisted laparoscopy is associated with the highest number of lymph nodes removed in early-stage ovarian cancer patients.

Objectives: To determine the difference in molecular signatures specific to ovarian endometrioid carcinoma and endometrial endometrioid carcinoma using next-generation cancer genomic sequencing data. Methods: Next-generation sequencing data for ovarian endometrioid carcinoma and endometrial endometrioid carcinoma were obtained from the American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (Project GENIE). All specimens were assessed for the occurrence of any molecular alteration within the most frequently mutated genes in both tumor types. Multivariable logistic regression was then used to determine molecular predictive models specific to ovarian endometrioid carcinoma versus endometrial endometrioid carcinoma. Results: The top 105 mutated genes in both tumor types were queried in 1,813 total tumor specimens, including 181 ovarian endometrioid carcinoma and 1,632 endometrial endometrioid carcinoma. Mutations in the following genes were positively associated with the ovarian endometrioid carcinoma histology (odds ratio, 95% CI, p-value): CTNNB1 (1.728, 1.226-2.435, 0.002), MGA (3.248, 1.653-6.379, <0.001), KDM6B (4.082, 1.385-12.027, 0.011), CIITA (2.758, 1.210-6.288, 0.016), and ENG (6.637, 1.591-27.695, 0.009). Mutations in the following genes were positively associated with the endometrial endometrioid carcinoma histology (odds ratio, 95% CI, p-value): PIK3CA (1.469, 1.037-2.082, 0.030), PTEN (2.997, 2.079-4.319, <0.001), PIK3R1 (1.935, 1.176-3.186, 0.009), CTCF (2.105, 1.091-4.065, 0.027), ZFHX3 (2.890, 1.123-7.440, 0.028), and BCOR (3.753, 1.809-7.786, <0.001). Objectives: To determine the difference in molecular signatures specific to ovarian endometrioid carcinoma and endometrial endometrioid carcinoma using next-generation cancer genomic sequencing data. Methods: Next-generation sequencing data for ovarian endometrioid carcinoma and endometrial endometrioid carcinoma were obtained from the American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (Project GENIE). All specimens were assessed for the occurrence of any molecular alteration within the most frequently mutated genes in both tumor types. Multivariable logistic regression was then used to determine molecular predictive models specific to ovarian endometrioid carcinoma versus endometrial endometrioid carcinoma. Results: The top 105 mutated genes in both tumor types were queried in 1,813 total tumor specimens, including 181 ovarian endometrioid carcinoma and 1,632 endometrial endometrioid carcinoma. Mutations in the following genes were positively associated with the ovarian endometrioid carcinoma histology (odds ratio, 95% CI, p-value): CTNNB1 (1.728, 1.226-2.435, 0.002), MGA (3.248, 1.653-6.379, <0.001), KDM6B (4.082, 1.385-12.027, 0.011), CIITA (2.758, 1.210-6.288, 0.016), and ENG (6.637, 1.591-27.695, 0.009). Mutations in the following genes were positively associated with the endometrial endometrioid carcinoma histology (odds ratio, 95% CI, p-value): PIK3CA (1.469, 1.037-2.082, 0.030), PTEN (2.997, 2.079-4.319, <0.001), PIK3R1 (1.935, 1.176-3.186, 0.009), CTCF (2.105, 1.091-4.065, 0.027), ZFHX3 (2.890, 1.123-7.440, 0.028), and BCOR (3.753, 1.809-7.786, <0.001).

PURPOSE Hyperthermic intraperitoneal chemotherapy (HIPEC) confers a survival benefit in epithelial ovarian cancer (EOC) and in preclinical models. However, the molecular changes induced by HIPEC have not been corroborated in humans. PATIENTS AND METHODS A feasibility trial evaluated clinical and safety outcomes of HIPEC with cisplatin during optimal cytoreductive surgery (CRS) in patients with EOC diagnosed with stage III, IV, or recurrent EOC. Pre- and post-HIPEC biopsies were comprehensively profiled with genomic and transcriptomic sequencing to identify mutational and RNAseq signatures correlating with response; the tumor microenvironment was profiled to identify potential immune biomarkers; and transcriptional signatures of tumors and normal samples before and after HIPEC were compared to investigate HIPEC-induced acute transcriptional changes. RESULTS Thirty-five patients had HIPEC at the time of optimal CRS; all patients had optimal CRS. The median progression-free survival (PFS) was 24.7 months for primary patients and 22.4 for recurrent patients. There were no grade 4 or 5 adverse events. Anemia was the most common grade 3 adverse event (43%). Hierarchical cluster analyses identified distinct transcriptomic signatures of good versus poor responders to HIPEC correlating with a PFS of 29.9 versus 7.3 months, respectively. Among good responders, significant HIPEC-induced molecular changes included immune pathway upregulation and DNA repair pathway downregulation. Within cancer islands, % programmed cell death protein 1 expression in CD8+ T cells significantly increased after HIPEC. An exceptional responder (PFS 58 months) demonstrated the highest programmed cell death protein 1 increase. Heat shock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors. CONCLUSION Distinct transcriptomic signatures identify responders to HIPEC, and preclinical model findings are confirmed for the first time in a human cohort.

Objectives: To determine if hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival in patients undergoing cytoreductive surgery (CRS) for newly diagnosed stage III or stage IV ovarian cancer at Commission on Cancer (CoC)-accredited cancer programs in the United States. Methods: The National Cancer Database was queried for patients with stage III or stage IV ovarian cancer undergoing CRS+HIPEC between 2004 and 2017. A control population of patients from 38 HIPEC-performing institutions undergoing CRS only was obtained using propensity score matching and adjusted for facility volume, age, Charlson-Deyo-Comorbidity-Index (CDCI), and stage. All patients in this study underwent complete cytoreduction to no gross residual (NGR) disease. Univariate survival analyses were performed using the log-rank test and adjusted for covariates using Cox proportional hazards regression. All analyses were performed using IBM SPSS Statistics 27. Results: A total of 66 patients who underwent CRS+HIPEC and had available survival data were identified. An additional 66 patients who underwent CRS only at HIPEC performing institutions were included in all comparisons based on propensity score match parameters. Demographics for the CRS+HIPEC group versus the CRS only group revealed no significant difference between median age (58 vs 61 years old) or median CDCI (score 0 vs 0), while significant differences were observed in primary CRS (46% vs 76%) (p<0.001), interval CRS (54% vs 24%) (p<0.001), stage III (65% vs 82%) (p=0.007), and stage IV (35% vs 18%) (p=0.007). Patients undergoing CRS+HIPEC had a significantly higher median overall survival (OS) of 42.1 months (95% CI: 31.8-52.4 months) compared to patients undergoing CRS only, who had a median OS of 34.9 months (95% CI: 23.4-46.4 months, p=0.015). Fifty percent of patients undergoing CRS+HIPEC were still alive at 60 months compared to 30.3% of patients undergoing CRS only. On multivariable analysis, patients undergoing CRS+HIPEC were 38.9% less likely to die compared to those who underwent CRS alone (HR of death: 0.611, 95% CI 0.402-0.928, p=0.021). Conclusions: On retrospective review of patients undergoing complete CRS for newly diagnosed stage III or stage IV ovarian cancer at CoC-accredited cancer programs in the United States, we found CRS+HIPEC to be associated with significantly improved survival compared to CRS only. These findings are especially notable given the higher proportion of stage IV patients in the CRS+HIPEC group. Thus, stage IV patients who respond well to neoadjuvant chemotherapy and can undergo complete interval CRS should also be considered for HIPEC. Objectives: To determine if hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival in patients undergoing cytoreductive surgery (CRS) for newly diagnosed stage III or stage IV ovarian cancer at Commission on Cancer (CoC)-accredited cancer programs in the United States. Methods: The National Cancer Database was queried for patients with stage III or stage IV ovarian cancer undergoing CRS+HIPEC between 2004 and 2017. A control population of patients from 38 HIPEC-performing institutions undergoing CRS only was obtained using propensity score matching and adjusted for facility volume, age, Charlson-Deyo-Comorbidity-Index (CDCI), and stage. All patients in this study underwent complete cytoreduction to no gross residual (NGR) disease. Univariate survival analyses were performed using the log-rank test and adjusted for covariates using Cox proportional hazards regression. All analyses were performed using IBM SPSS Statistics 27. Results: A total of 66 patients who underwent CRS+HIPEC and had available survival data were identified. An additional 66 patients who underwent CRS only at HIPEC performing institutions were included in all comparisons based on propensity score match parameters. Demographics for the CRS+HIPEC group versus the CRS only group revealed no significant difference between median age (58 vs 61 years old) or median CDCI (score 0 vs 0), while significant differences were observed in primary CRS (46% vs 76%) (p<0.001), interval CRS (54% vs 24%) (p<0.001), stage III (65% vs 82%) (p=0.007), and stage IV (35% vs 18%) (p=0.007). Patients undergoing CRS+HIPEC had a significantly higher median overall survival (OS) of 42.1 months (95% CI: 31.8-52.4 months) compared to patients undergoing CRS only, who had a median OS of 34.9 months (95% CI: 23.4-46.4 months, p=0.015). Fifty percent of patients undergoing CRS+HIPEC were still alive at 60 months compared to 30.3% of patients undergoing CRS only. On multivariable analysis, patients undergoing CRS+HIPEC were 38.9% less likely to die compared to those who underwent CRS alone (HR of death: 0.611, 95% CI 0.402-0.928, p=0.021). Conclusions: On retrospective review of patients undergoing complete CRS for newly diagnosed stage III or stage IV ovarian cancer at CoC-accredited cancer programs in the United States, we found CRS+HIPEC to be associated with significantly improved survival compared to CRS only. These findings are especially notable given the higher proportion of stage IV patients in the CRS+HIPEC group. Thus, stage IV patients who respond well to neoadjuvant chemotherapy and can undergo complete interval CRS should also be considered for HIPEC.

5542 Background: Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. MIRV has promising single agent activity in FRα-positive medium/high expression epithelial ovarian cancer (EOC), at 6 mg/kg, based on adjusted ideal body weight (AIBW) IV every (q) 21 days. This study evaluated MIRV and G in recurrent EOC, endometrial and triple negative breast cancer. The recommended phase 2 dose (RP2D) was established at MIRV 6 mg/kg AIBW IV, day 1 and G 800 mg/m2 IV, d1, 8 q21 days (J Clin Oncol 37, 2019, Abs. #3009). Here we report the results from the EOC cohort. Methods: Patients (pts) with FRα-positive platinum resistant EOC with ≤4 prior chemotherapy (CT) regimens, were eligible. FRα positivity was initially defined as ≥ 25% of cells with PS2+ staining intensity (low to high FRα expression) and was subsequently revised to require medium/high FRα expression (≥50%/ ≥75% of cells with PS2+ staining intensity). Results: From 10/2017 to 12/2020, 113 EOC pts underwent FRα screening, with 74 FRα-positive results. Thirty total EOC pts (with median 3 prior lines of therapy) were treated; 8 pts during dose escalation and 22 EOC pts at the RP2D (all evaluable for response). Fifteen (50%) pts had high FRα, 10 pts (33%) medium FRα, and 5 pts (17%) low FRα expression. Eleven (36%) of the 30 EOC pts achieved a partial response (PR), 15 pts (50%) had SD and 4 pts (13%) progressed. Among the 11 responders, 5 pts had high FRα, 4 pts medium FRα and 2 pts low FRα expression. Non-heme clinically significant adverse events (AEs) included: G2 sensory neuropathy (4 pts) G3 diarrhea (3 pts), G3 fatigue (2 pts), G3 pneumonitis (2 pts), and 1 pt with G5 respiratory failure (secondary to pneumonia but drug-induced pneumonitis could not be ruled out). Conclusions: MIRV in combination with G has promising clinical activity in late line platinum resistant FRα-positive EOC, with best responses observed in high FRα expression. The regimen is well tolerated with expected AEs based on the known toxicities of each agent. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by ImmunoGen Corp and Cancer Center Support Grant P30CA033572. Clinical trial information: NCT02996825.

Objectives: To demonstrate safety and tolerability of HIPEC in ovarian cancer. Methods: A phase I, single-institution feasibility study was designed to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS) in ovarian cancer patients, followed by optional normothermic intraperitoneal chemotherapy, at City of Hope National Comprehensive Cancer Center (Duarte, CA). Primary endpoint of the trial was to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS). Progression-free survival was a secondary end-point. Exploratory endpoints included the assessment of molecular markers in tumors. Eligibility criteria included epithelial ovarian cancer (stage III or IV), primary or recurrent, ECOG 0-1, and appropriate surgical candidates. 35 patients were enrolled between 2015 and 2019, who underwent optimal CRS (gross residual disease less than 1 cm), and received HIPEC intra-operatively with cisplatin at 75 mg/m2 for 60 minutes immediately following optimal CRS. Patients were stratified as either 1) primary disease (n=19), defined as having received HIPEC at time of interval CRS following neoadjuvant chemotherapy for primary EOC; 2) recurrent disease (n=16), defined as having received HIPEC at time of interval or upfront CRS for recurrent (salvage) EOC. Adjuvant chemotherapy was given at the discretion of the treating oncologist following HIPEC. Results: Median age was 58 years (36-74 years), with a mean BMI of 26. Primary (interval) patients represented 54% of patients, with pretreatment clinical stages III (53%) and IV (47%). Recurrent (salvage) patients represented 45.7%, with platinum-sensitive (75%) and platinum-resistant (25%). The most common histological subtype was high grade serous (69%). All primary (interval) patients underwent neoadjuvant chemotherapy (3-4 cycles) prior to interval CRS and HIPEC. The majority of recurrent patients (81%) did not receive neo-adjuvant chemotherapy. Thirty-three patients underwent closed technique and two underwent laparoscopic technique. Total mean operating time was 8.4 hours (4.6-15.3). Mean length of stay was 10 days (3-30). All patients underwent optimal cytoreduction (69% with complete R0 resection). Peritoneal carcinomatosis index (PCI) ranged 2 to 30 (median of 8). Patients with PCI < 8 had significantly improved PFS of 26.9 months compared to PCI >/= 8 whose PFS was 12.6 (p=0.04). Time to initiation of adjuvant chemotherapy in recurrent patients was 8.4 weeks. 22.9% of the ovarian cancer cohort was gBRCA mutated. Median PFS for primary patients was 12.6 months (95% CI 6.4; NR); with median follow up of 22.1 months (95% CI 12.6, 31.5). Median PFS for recurrent patients was 18.8 months (95% CI 7.2; 28.7), with median follow up of 36.3 months (95% CI 21.1, 51.5). There were no grade 4 or 5 AEs. Anemia was the most common Grade 3 AE (43%), followed by liver dysfunction and electrolyte abnormalities. The most common AE of any grades were abdominal pain (86%), anemia (77%), and nausea (66%). Two patients (6%) had grade 3 acute kidney injury and one patient had grade 3 chronic kidney disease. Sodium thiosulfate was introduced to the trial in January 2018, following which there were no grade 1-4 acute or chronic kidney injuries. Conclusions: HIPEC in ovarian cancer was well tolerated, without any grade 4 or 5 AEs. Renal toxicities were mitigated with sodium thiosulfate. Patients with a low PCI (< 8) had better PFS than those with PCI >/= 8. To demonstrate safety and tolerability of HIPEC in ovarian cancer. A phase I, single-institution feasibility study was designed to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS) in ovarian cancer patients, followed by optional normothermic intraperitoneal chemotherapy, at City of Hope National Comprehensive Cancer Center (Duarte, CA). Primary endpoint of the trial was to evaluate the safety and feasibility of HIPEC at time of optimal cytoreductive surgery (CRS). Progression-free survival was a secondary end-point. Exploratory endpoints included the assessment of molecular markers in tumors. Eligibility criteria included epithelial ovarian cancer (stage III or IV), primary or recurrent, ECOG 0-1, and appropriate surgical candidates. 35 patients were enrolled between 2015 and 2019, who underwent optimal CRS (gross residual disease less than 1 cm), and received HIPEC intra-operatively with cisplatin at 75 mg/m2 for 60 minutes immediately following optimal CRS. Patients were stratified as either 1) primary disease (n=19), defined as having received HIPEC at time of interval CRS following neoadjuvant chemotherapy for primary EOC; 2) recurrent disease (n=16), defined as having received HIPEC at time of interval or upfront CRS for recurrent (salvage) EOC. Adjuvant chemotherapy was given at the discretion of the treating oncologist following HIPEC. Median age was 58 years (36-74 years), with a mean BMI of 26. Primary (interval) patients represented 54% of patients, with pretreatment clinical stages III (53%) and IV (47%). Recurrent (salvage) patients represented 45.7%, with platinum-sensitive (75%) and platinum-resistant (25%). The most common histological subtype was high grade serous (69%). All primary (interval) patients underwent neoadjuvant chemotherapy (3-4 cycles) prior to interval CRS and HIPEC. The majority of recurrent patients (81%) did not receive neo-adjuvant chemotherapy. Thirty-three patients underwent closed technique and two underwent laparoscopic technique. Total mean operating time was 8.4 hours (4.6-15.3). Mean length of stay was 10 days (3-30). All patients underwent optimal cytoreduction (69% with complete R0 resection). Peritoneal carcinomatosis index (PCI) ranged 2 to 30 (median of 8). Patients with PCI < 8 had significantly improved PFS of 26.9 months compared to PCI >/= 8 whose PFS was 12.6 (p=0.04). Time to initiation of adjuvant chemotherapy in recurrent patients was 8.4 weeks. 22.9% of the ovarian cancer cohort was gBRCA mutated. Median PFS for primary patients was 12.6 months (95% CI 6.4; NR); with median follow up of 22.1 months (95% CI 12.6, 31.5). Median PFS for recurrent patients was 18.8 months (95% CI 7.2; 28.7), with median follow up of 36.3 months (95% CI 21.1, 51.5). There were no grade 4 or 5 AEs. Anemia was the most common Grade 3 AE (43%), followed by liver dysfunction and electrolyte abnormalities. The most common AE of any grades were abdominal pain (86%), anemia (77%), and nausea (66%). Two patients (6%) had grade 3 acute kidney injury and one patient had grade 3 chronic kidney disease. Sodium thiosulfate was introduced to the trial in January 2018, following which there were no grade 1-4 acute or chronic kidney injuries. HIPEC in ovarian cancer was well tolerated, without any grade 4 or 5 AEs. Renal toxicities were mitigated with sodium thiosulfate. Patients with a low PCI (< 8) had better PFS than those with PCI >/= 8.

Background Immunogenic cell death has been suggested as a mechanism for HIPEC, through the release of heat shock proteins, and resulting in activation of tumor-specific T cells. Methods This is a subgroup analysis of a Phase I trial using HIPEC with cisplatin 75 mg/m2 at time of optimal cytoreduction. Metastatic tumors from nine ovarian cancer patients were collected intraoperatively before and after HIPEC. Differentially expressed genes and pathways of pre- and post-HIPEC tumors were analyzed via whole-transcriptome sequencing (WTS). Immunofluorescent (IF) staining and multispectral imaging were used to determine composition and PD-1 expression of CD8+ and conventional CD4+ tumor-infiltrating lymphocytes (TILs), using antibodies against CD8, FOXP3, PD-1, and pancytokeratin (to distinguish cancer islands from stroma). Kaplan-Meier and log-rank tests compared the overall and progression free survivals (PFS) of patients with low versus high%PD-1 changes, based on dichotomization with respect to the median%PD-1 change. Results Heatshock proteins comprised the top differentially upregulated genes in HIPEC-treated tumors. Gene set enrichment analysis revealed significant upregulation of immune pathways, including antigen processing/presentation. IF staining demonstrated increased%PD-1 in cancer islands of CD8+ and CD4+ TILs after HIPEC. In stroma, the largest%PD-1 change occurs in an exceptional responder (PFS, OS 5 years), while the lowest%PD-1 change occurred in a poor responder. Kaplan-Meier curves demonstrate superior PFS in patients with high stromal PD-1 changes in TILs after HIPEC. Conclusions Increased PD-1 expression after HIPEC suggests early HIPEC-induced T cell activation, and is associated with improved survival, implicating a potential future role for PD-1 inhibitors following HIPEC in ovarian cancer.

Mirvetuximab soravtansine (MIRV) is an ADC comprising a FRα-binding antibody, linked to the tubulin-disrupting maytansinoid DM4. MIRV has promising single agent activity in FRα-positive epithelial ovarian cancer (EOC), at 6 mg/kg, based on adjusted ideal body weight (AIBW) IV every (q) 21 days. Clinical data in other FRα-positive solid tumors has been limited. This study is evaluating MIRV and G in recurrent EOC, EC and triple negative breast cancer (TNBC). The recommended phase II dose (RP2D) reported at ASCO 2019, was established at DL3 (MIRV 6 mg/kg AIBW IV, day 1 and G 800 mg/m2 IV, d1, 8) q21 days. Here we report the results in the EC cohort treated at the RP2D. Pts with FRα-positive EC with ≤ 2 prior chemotherapy (CT) regimens are eligible. FRα positivity by immunohistochemistry was initially defined as ≥25% of cells with PS2+ staining intensity (low to high FRα levels) and was subsequently revised to ≥ 50% of cells with PS2+ (medium/high FRα levels, with high defined as ≥ 75% of cells with PS2+). The expansion cohort of 12 pts with FRα-positive EC treated at the RP2D pre-specified that ≥ 2 responders are required to declare the combination promising. From October 2017 to May 2020, 55 EC pts underwent FRα screening, with 4 results pending. Out of 51 EC pts with results, 12 pts (23.5%) have medium/high FRα levels with 5 pts (9.8%) have low FRα level. 5 EC pts were treated at the RP2D (1 too early and 4 evaluable for response of which 1 pt had medium FRα and 3 pts had low FRα). 2 of the 4 evaluable EC pts at the RP2D achieved a partial response (PR). 1 PR was observed on cycle 7 (the only medium FRα level pt) and the second PR was on cycle 3. One pt. had SD after 4 cycles and remains on treatment, and 1 pt progressed in the 1st cycle. Grade (G) 3-4 adverse events (AEs) in the 4 evaluable pts treated at the RP2D were infrequent and included: Gr 4 lymphopenia (1 pt), Gr 3 ANC/WBC/PLT (1 pt), and Gr 3 HTN and lymphopenia (1pt). The combination of MIRV with G has promising clinical activity in FRα-positive EC. The regimen is tolerable with the expected treatment related AEs of these agents.

To evaluate intraperitoneal (IP) nab-paclitaxel in patients with advanced malignancies that are primarily confined to the peritoneal cavity in a phase I trial. Using a 3 + 3 dose escalation of IP nab-paclitaxel on days 1, 8, and 15 of a 28-day cycle, we evaluated six dose levels (35–175 mg/m2/dose). Maximum tolerated dose (MTD) and pharmacokinetics (PK) of IP nab-paclitaxel were determined. There were no dose-limiting toxicities (DLTs) in cohorts 1–3. There was a DLT in one of six patients in cohort 4 (112.5 mg/m2) (grade 3 neutropenia causing treatment delay > 15 days) and a DLT in one of three patients in cohort 6 (175 mg/m2) (grade 4 neutropenia and grade 3 abdominal pain). A second patient in cohort 6 experienced a serious adverse event (cycle 1, grade 4 ANC ≤ 7 days, cycle 4, grade 2 left ventricular dysfunction). This dose level was determined to be above the MTD. No DLTs were seen in seven patients treated in cohort 5 (140 mg/m2). The MTD of IP nab-paclitaxel was established at 140 mg/m2 on days 1, 8, and 15 of a 28-day cycle. There was a PK advantage for IP nab-paclitaxel, with an IP plasma area under the concentration–time curve (AUC) ratio of 147-fold (range 50–403) and therapeutic range systemic drug levels. Eight of 27 enrolled patients had progression-free survival ≥ 6 months. One patient experienced complete response, and one patient experienced partial response. Six patients had stable disease. Weekly IP nab-paclitaxel has a favorable toxicity profile, a significant pharmacologic advantage, and promising clinical activity. NCT00825201.

3009 Background: IMGN853 is an antibody-drug conjugate targeting the folate receptor alpha (FOLR1), linked to maytansinoid, DM4. IMGN853 has promising single agent activity in FOLR1+ EOC. The recommended phase 2 dose (RP2D) is 6 mg/kg, based on adjusted ideal body weight (AIBW) IV every 3 wks. This study evaluates IMGN853 and G. Methods: Patients (pts) with FOLR1+ tumors including: platinum resistant EOC with ≤4 prior chemotherapy (CT) regimens, EC with ≤2 CT and TNBC ≤4 CT are eligible. FOLR1 + is defined as ≥25% of tumor staining (all tumors) ≥2+ intensity (EOC, EC) and ≥1+ (TNBC). A standard 3+3 design combines IMGN853 and G. EOC pts undergo one research biopsy to assess intratumoral vs. circulating DM4 level and biopsy vs. archival tissue FOLR1 expression. Dose-limiting toxicity (DLT) is assessed during cycle 1. Responses as per RECIST 1.1 are assessed at 12 wks. and adverse events (AEs) are evaluated by CTCAE v4.0. Results: From 10/2017 to 1/2019 a total of 15 pts. were treated (3 additional pts have consented on dose level [DL] 4):10 EOC, 3 EC and 2 TNBC. One pt. on DL1 had grade (G) 4 thrombocytopenia (PLT) DLT. Three pts were inevaluable for DLT and were replaced: 1 pt. at DL1 with G4 neutropenia without fever of unknown duration due to delayed follow up blood work, 1 pt. at DL2 and 1 pt. at DL3 due to incomplete cycle 1. No DLTs were observed on DL2-3. Day 8 cycle 1 dose modifications were required in 3 of 4 patients on DL3 (for mucositis [1 pt.], and PLT [2 pts]). We are now enrolling at the RP2D for both agents, and MTD will be determined prior to May 2019. Conclusions: IMGN853 in combination with G is achievable at clinically relevant doses and the recommended Phase 2 dose and MTD will be reported. Support: NCCN grant; with support from ImmunoGen Corp and Cancer Center Support Grant P30CA033572. Clinical trial information: NCT02996825. [Table: see text]

Vulvar cancer is a rare malignancy with high curability in early-stage disease, yet poor outcomes for advanced-stage and recurrent disease. Surgical management is at the cornerstone of treatment for most vulvar cancers, and includes conservative and radical resection of the primary vulvar tumor and excision of local lymph nodes, which are major prognostic factors and drive adjuvant treatment. This review summarizes the surgical management of primary squamous cell carcinoma of the vulva, specifically initial treatment guidelines by stage, based on the 2017 NCCN Clinical Practice Guidelines in Oncology for Vulvar Cancer.

2553 Background: nab-Paclitaxel is albumin-bound paclitaxel that achieves higher intratumoral concentrations and undergoes receptor-mediated transcytosis across cell membranes. Previous clinical trials have demonstrated an advantage to IP chemotherapy. A phase I study was undertaken to evaluate the safety, tolerability and pharmacokinetics of IP nab-paclitaxel. Methods: Eligible pts received IP nab-paclitaxel on D1, 8, 15 of a 28-day cycle with a 3+3 dose-escalation design. Plasma and peritoneal pharmacokinetic (PK) samples were drawn prior to dose, immediately upon completion of infusion, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose on C1D1 and C1D15. Results: The trial is complete with 27 pts with peritoneal carcinomatosis secondary to GYN (n=14), GI (n=12) malignancies and 1 pt with peritoneal mesothelioma. The starting dose level was 35mg/m2 and escalated to 170mg/m2. The MTD of IP nab-paclitaxel was established at 140 mg/m2. DLTs included grade 3 neutropenia resulting in treatment delay >15 days, grade 3 abdominal pain and grade 4 neutropenia > 7 days. Plasma and IP PK data are summarized below in the Table. Over the four dose levels, the data show a ~150-fold PA to IP nab-paclitaxel with low intra-pt variability. The lowest PA was 50-fold. Conclusions: PK results suggest a significant PA to IP nab-paclitaxel (i.e. higher peritoneal exposure compared to plasma).The inter- and intra-patient variability appears to be low. The plasma AUC's resulting from IP nab-paclitaxel at the MTD of 140 mg/m2 are similar to plasma AUC's associated with IV nab-paclitaxel at 100 mg/m2. In addition to achieving high local drug levels in the peritoneum, patients are also exposed to therapeutic systemic drug levels. This study was funded by the National Comprehensive Cancer Network (NCCN) with support from Celgene Corporation. Clinical trial information: NCT00825201. nab-Paclitaxel Dose (mg/m2) N Treatment Day Plasma AUC (mg/L x hr) Peritoneal AUC (mg/L x hr) Ratio (%) 35 1 Cycle 1 Day 1 0.6 89 160 Cycle 1 Day 15 0.5 93 172 70 1 Cycle 1 Day 1 1.5 299 194 Cycle 1 Day 15 1.6 321 199 90 1 Cycle 1 Day 1 1.1 207 94 Cycle 1 Day 15 1.1 194 72 112.5 3 Cycle 1 Day 1 3.0 (0.8-4.2) 305 (210-427) 134 (50-389) Cycle 1 Day 15 2.5 (0.6-3.2) 290 (230-358) 118 (88-403)

Intraperitoneal chemotherapy poses both potential benefits as a cancer treatment and negative consequences on patient and family quality of life.The profound multi-dimensional quality of life impact of intraperitoneal (IP) chemotherapy upon women with advanced ovarian cancer makes the early integration of palliative care particularly important for this population. Numerous opportunities occur throughout the treatment process to improve the delivery of biopsychosocial-spiritual support to women receiving IP chemotherapy.

PURPOSE OF THE RESEARCH:Intraperitoneal (IP) chemotherapy is a viable and superior treatment to standard intravenous (IV) chemotherapy in women with small volume residual ovarian cancer following optimal debulking. Despite this clinical advantage, widespread adoption of the treatment regimen has been hampered by concerns related to toxicities and complications. The purpose of this descriptive study was to describe nursing implications related to toxicities, complications and clinical encounters in 17 women with ovarian cancer who received IP chemotherapy.METHODS AND SAMPLE:Women with ovarian cancer who received IP chemotherapy at one NCI-designated comprehensive cancer center were accrued. Data related to IP chemotherapy summary, clinical encounters and admissions were obtained through comprehensive chart audits.KEY RESULTS:Common treatment-related toxicities included nausea and vomiting, fatigue, hypomagnesia, pain, neuropathy, anemia, and constipation. Reasons for dose-modifications were multi-factorial, and were primarily related to catheter complications and chemotherapy toxicities. The number of clinical encounters was high, and they were primarily related to admissions for inpatient IP chemotherapy and follow-up clinic visits.CONCLUSIONS:Treatment-related toxicities and complications were common in women with ovarian cancer who received IP chemotherapy. Use of IP chemotherapy results in multiple clinical encounters, such as outpatient clinic visits and inpatient admissions. Nursing is a critical part of the interdisciplinary approach in caring for women treated with IP chemotherapy. Interdisciplinary teams with high levels of knowledge and skills related to IP chemotherapy administration are needed to manage treatment-related toxicities and complications, and support multiple clinical encounters during treatment.