bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601).
Authors: Antill Yoland Catherine , Kok Peey Sei , Robledo Kristy , Barnes Elizabeth , Friedlander Michael , Baron-Hay Sally E. , Shannon Catherine M. , Coward Jermaine , Beale Philip James , Goss Geraldine , Meniawy Tarek , Yip Sonia , Smith Deborah , Spurdle Amanda B. , Parry Michelle , Andrews John , Kelly Marzena , Stockler Martin R. , Mileshkin Linda R. ,   Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Published: May 2019

5501

Background: Deficient DNA mismatch repair (dMMR) occurs in approximately 15% of AEC and is associated with a high tumour mutation burden. Expression of PD-1 and PD-L1 has been reported in up to 90% of ECs, including those with proficient DNA mismatch repair (pMMR). We report here preliminary results of PHAEDRA, a single-arm phase 2 trial designed to determine the activity of single-agent durvalumab, an antibody to PD-L1, in 2 cohorts of women with AEC. Methods: Participants (pts) had pMMR AEC progressing after 1-3 lines of chemotherapy, or dMMR AEC progressing after 0-3 lines of chemotherapy, and were treated with durvalumab 1500mg IV Q4W. The primary endpoint was objective tumour response (OTR = complete response [CR] or partial response [PR] by iRECIST). Secondary endpoints included disease control at 16 weeks (DC16w = CR, PR, or stable disease at 16 weeks [SD16w]), immune-related adverse events (irAEs), PD-L1, germline mutations and MLH1 methylation. Other secondary endpoints include: OTR and DC by RECIST1.1, other AE, PFS, OS & quality of life will be reported later. Results: 71 pts with AEC were recruited from Feb 2017 to Sep 2018: 35 dMMR and 36 pMMR. Median follow-up were 8.3 vs 14.8 months in dMMR vs pMMR pts. Median age: 67 (range 36-81); ECOG PS: 0-1 in 68, and 2 in 3. Pathology: endometrioid in 94% and 58%; serous in 0% and 31%; grade: high in 42% and 83% (dMMR and pMMR respectively). Durvalumab was the 1st, 2nd and subsequent line of non-hormonal therapy in 15, 14, and 6 pts with dMMR and 0, 21, and 15 pts with pMMR. Among dMMR pts, the OTR rate was 40% (14/35, 95% CI 26-56), with 4 CR and 10 PR; 7 others had SD 16w for a DC16w rate of 60% (21/35, 95% CI 44-74). OTR rate was 40% as 1st line, 43% as 2nd line, and 33% as subsequent line treatment. Among pMMR pts, the OTR rate was 1/36 (3%, 95% CI 1-14) with 1 PR; 6 others had SD16w for a DC16w rate of 19% (7/36; 95% CI 10-35). IrAEs occurred in 14 pts: hyperthyroidism in 6, hypothyroidism in 6, pneumonitis in 1 and hepatitis in 1. Conclusions: Durvalumab monotherapy showed promising activity and safety in AEC with dMMR regardless of prior lines of chemotherapy, but there was limited evidence of activity in AEC with pMMR. Clinical trial information: ACTRN12617000106336.
Results from neoadjuvant chemotherapy followed by surgery compared to chemoradiation for stage Ib2-IIb cervical cancer, EORTC 55994.
Authors: Kenter Gemma , Greggi Stefano , Vergote Ignace , Katsaros Dionyssios , Kobierski Juliusz , Massuger Leon , van Doorn H. C. , Landoni Fabio , Van Der Velden Jacobus , Reed Nicholas Simon , Coens Corneel , van Luijk Iske , Ottevanger P. B. , Casado Antonio
Published: May 2019

5503

Background: Conflicting evidence on the value of neoadjuvant chemotherapy followed by surgery compared to concomitant chemoradiation in Stage IB2-IIB cervical carcinoma led to this multinational multicenter trial. As the trial is approaching completion of its follow-up, preliminary results are presented. Methods: Between May 2002 and June 2014 a total of 620 patients with FIGO stage Ib2-IIb were randomized between neoadjuvant chemotherapy followed by surgery (NACTS, arm 1, N=311) with standard concomitant chemoradiotherapy (CCRT, arm 2, N=309) . In arm 1, radical hysterectomy was required within 6 weeks after completion of cisplatin-based chemotherapy with a cumulative minimum of 225mg/m2, in arm 2, radiation consisted of 45-50 Gy plus boost concurrent with weekly cisplatin chemotherapy (40 mg/m2 per week). Primary endpoint was 5-yrs overall survival (OS). Results: Median follow-up time was 8.2 years ( 95% CI = 7.8 yrs – 8.6 yrs)) and similar between both arms. A total of 191 deaths (31%) occurred. Age, stage and histological cell type were balanced in both arms. Protocol treatment was completed in 459 (74%) patients (71% for NACTS; 82% for CCRT). In arm 1 238 (76%) patients underwent surgery. Main reasons for not having surgery as per protocol, were toxicity (25/74, 34%), progressive disease (18/74, 24%) and insufficient response to NACT (12/74, 16%). Additional radiotherapy was given to 113 patients (36.3%) in arm 1; additional surgery performed in 9 patients (2.9%) in arm 2. Short term severe adverse events (≥G3) occurred more frequently in arm 1 than in arm 2 (35% vs 21%, p < 0.001). The 5 year OS was 72% in arm 1 and 76% in arm 2 (not statistically significant, difference = 4.0% (95%CI: -4% - 12%); HR 0.87, 95%CI: 0.65-0.15, p=0.332). Conclusions: These preliminary results revealed no difference in 5-year OS between NACTS and CCRT, indicating that quality of life and long term toxicity are important to decide optimal treatment. The final results will be available by April 2019, including long-term toxicity and treatment effect across prognostic factors. Clinical trial information: NCT00039338.
Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.
Authors: Penson Richard T. , Villalobos Valencia Ricardo , Cibula David , Colombo Nicoletta , Leath Charles A. , Bidziński Mariusz , Kim Jae-Weon , Nam Joo-Hyun , Madry Radoslaw , Hernández Carlos Hernández , Mora Paulo Alexandre Ribeiro , Ryu Sang Young , Milenkova Tsveta , Lowe Elizabeth S. , Barker Laura , Scambia Giovanni
Published: May 2019

5506

Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m2 D1, D8, D15 q4w] or PLD [50 mg/m2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs >12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [ PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P=0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P=0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P<0.001; median 13.2 vs 8.5 months, respectively). Most common adverse events (AEs) with olaparib were nausea (65% vs 34% [TPC]) and anemia (50% vs 25%) and with TPC were palmar-plantar erythrodysesthesia (PPE; 36% vs 1% [olaparib]) and nausea. Most common grade ≥3 AEs in either arm were anemia (21% [olaparib] vs 0 [TPC]), PPE (0 vs 12%) and neutropenia (6% vs 11%). For olaparib vs TPC, serious AEs were reported by 24% vs 18% and AEs led to treatment discontinuation in 7% vs 20%. Conclusions: Pts with gBRCAm PSR OC receiving olaparib monotherapy had a significant, clinically relevant improvement in ORR and PFS vs TPC, with no new safety signals. Clinical trial information: NCT02282020.
EWOC-1: A randomized trial to evaluate the feasibility of three different first-line chemotherapy regimens for vulnerable elderly women with ovarian cancer (OC): A GCIG-ENGOT-GINECO study.
Authors: Falandry Claire , Savoye Aude Marie , Stefani Laetitia , Tinquaut Fabien , Lorusso Domenica , Herrstedt Jorn , Bourbouloux Emmanuelle , Floquet Anne , Brachet Pierre Emmanuel , Zannetti Alain , Mouret-Reynier Marie-Ange , Sverdlin Robert , D'hondt Veronique , Guillem Olivier , Cojocarasu Oana , Venat-Bouvet Laurence , Rousseau Frederique , Lortholary Alain , Pujade-Lauraine Eric , Freyer Gilles
Published: May 2019

5508

Background: The Geriatric Vulnerability Score (GVS) combining albumin, lymphocyte count, ADL, IADL and HADS scores has been reported (Falandry C Ann Oncol 2013) to identify vulnerable elderly OC patients (pts) as those with a GVS≥3. For such pts, Carboplatin (Cb) monotherapy or weekly Cb plus paclitaxel (Pa) are often proposed as an alternative to Cb-Pa given every 3 weeks. Methods: Pts ≥70 yrs with first line FIGO stage III/IV epithelial OC were screened for GVS. Those with GVS≥3 were randomized to receive either arm A: Cb AUC5-6 + Pa 175mg/m², d1q3week or arm B: Cb AUC5-6 d1q3week or arm C:weekly Cb AUC2 + Pa 60mg/m² d1-d8-d15 q4week. Primary endpoint is treatment feasibility defined as the ability to complete 6 chemotherapy courses without disease progression, early treatment stopping due to unacceptable toxicity or death. Inclusion of 240 pts was planned. Results: Among 444 screened pts, 120 were randomized from 12/2013 to 04/2017 (armA = B = C = 40). Pts characteristics were well balanced between arms A-B-C respectively: median age (79-82-80 yrs), FIGO stage IV (32-37-27%), primary surgery (65-72-70%), absence of macroscopic residuals (CC-0) (7-5-7%), ECOG≥2 (50-50-47%). Feasibility per protocol for arms A-B-C is 65%, 47% and 60% (p = 0.15). Main reasons for treatment arrest are treatment toxicity (A:20%; B:15%; C:22.5%; p = 0.771) and disease progression (A:7.5%; B:30%; C:2%; p = 0.004). Median PFS for arm A-B-C are 12.5 mos (95%CI 10.3-15.3), 4.8 (3.8-15.3) and 8.3 (6.6-15.3), respectively (p < 0.001) and median OS for arm A-B-C is not reached (NR) (21, NR), 7.4 (5.3-NR) and 17.3 (10.8-NR), respectively (p = 0.001). At the pre-planned intermediate analysis, the IDMC recommended to prematurely close the study as survival in armB was found significantly worse and the number of potential pts required to find a significant difference between both Cb-Pa regimens (arms A&C) was out of reach. Conclusions: Compared to 3-weekly and weekly Cb-Pa regimens, Cb single agent was reported to be less active with significant worse survival outcome in vulnerable elderly pts. In this population Cb-Pa combination remains a standard. Clinical trial information: NCT02001272.
Sex hormone, insulin, and insulin-like growth factor signaling in recurrence of high stage endometrial cancer: Results from the NRG Oncology/Gynecologic Oncology Group 210 trial.
Authors: Huang Gloria S. , Merritt Melissa A. , Hutson Alan , Strickler Howard D. , Einstein Mark , Brouwer-Visser Jurriaan , Ramirez Nilsa C. , Lankes Heather A. , El-Bahrawy Mona , Xue Xiaonan , Yu Herbert , Mannel Robert S. , O'Malley David M. , Mutch David Gardner , Disilvestro Paul , Geller Melissa Ann , Guntupalli Saketh R , Birrer Michael J. , Miller David S. , Gunter Marc J.
Published: May 2019

5509

Background: Sex hormone and insulin/insulin-like growth factor (IGF) axis signaling pathways play an important role in endometrial cancer development but their role in endometrial cancer recurrence is unknown. In this study GOG-8015 we evaluated these pathways in a prospective cohort of patients diagnosed with the most common type of endometrial cancer, endometrioid adenocarcinoma. Methods: Stage II-IV endometrioid endometrial adenocarcinoma patients (N = 816) enrolled in the GOG-210 study with pre-treatment specimens were tested for tumor mRNA and protein expression levels of IGF1, IGF2, IGF binding proteins ( IGFBP) -1and -3, the insulin (IR) and IGF-I receptors (IGF1R), and phosphorylated (activated) IR/IGF1R as well as estrogen (ER) and progesterone receptors (PR) using quantitative PCR and immunohistochemistry (IHC). Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone and sex hormone binding globulin were measured using ELISAs. Hazard ratios (HR) and 95% confidence intervals (CI) for risk of recurrence were obtained from multivariable Cox proportional hazard’s models with adjustment for age, stage and grade. Results: Recurrence occurred in 280 (34%) cases during a mean of 5.4 years of follow-up. ER-positivity (HR 0.67, 95% CI 0.47-0.95), IR-positivity (HR 0.53, 95% CI 0.29-0.98) and serum IGF-I levels (highest versus lowest quartile, HR 0.66, 95% CI 0.47-0.92) were inversely associated with recurrence risk. Conversely, circulating estradiol (highest versus lowest tertile, HR 1.55, 95% CI 1.02-2.36) and insulin (per 10 uU/ml, HR 1.52, 95% CI 1.12-2.06) and phosphorylated IGF1R/pIR expression (HR 1.40, 95% CI 1.02-1.92) were associated with increased risk of recurrence. Conclusions: We identified novel sex hormone and insulin/IGF axis tissue and circulating biomarkers of recurrence in a prospective study of high stage endometrioid endometrial cancer. Circulating insulin and estradiol, and tissue phosphorylated (activated) IGR1R/IR were independently associated with recurrence. These findings support prioritizing studies to establish their clinical utility as prognostic biomarkers and to investigate new strategies that target these pathways for prevention and treatment of endometrial cancer recurrence.
Impact of adding nintedanib to neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC) patients: The CHIVA double-blind randomized phase II GINECO study.
Authors: Ferron Gwenael , De Rauglaudre Gaetan , Chevalier Annick , Combe Pierre , Joly Florence , Lortholary Alain , Raban Nadia , Hamizi Salima , Malaurie Emmanuelle , Kaminsky Marie-Christine , Pautier Patricia , Meunier Jérome , Alexandre Jérôme , Berton-Rigaud Dominique , Floquet Anne , Venat-Bouvet Laurence , Favier Laure , Dohollou Nadine , Dubot Coraline , Ray-Coquard Isabelle Laure
Published: May 2019

5512

Background: Nintedanib, an oral inhibitor of VEGF-FGF-PDGF receptors, has been shown to prolong progression-free survival (PFS) when added to adjuvant chemotherapy after primary surgery (duBois A, Lancet Oncol 2015). CHIVA trial explored the role of nintedanib in combination with NACT. Methods: Patients (pts) with FIGO stage IIIC-IV chemotherapy-naive AEOC considered as unresectable after laparoscopic evaluation were randomized (2:1) to be treated with 3 to 4 cycles (cy) of carboplatin (AUC 5 mg/mL/min) and paclitaxel (175 mg/m²) (CP) before interval debulking surgery (IDS) followed by 2 to 3 cy of CP for a total of 6 cy, plus either 200 mg of Nin (armA) or placebo (armB) twice daily on days 2–21 q3week at cy 1&2, 5&6 and maintenance therapy for up to 2 years. The primary endpoint was PFS. Results: Between Jan. 2013 and May 2015, 188 pts were included (124 arm A, 64 arm B) with a median Peritoneal Cancer Index of 22 (range 19-27). Pts characteristics were well balanced between both arms. Median PFS was 14.4 mos (95%CI 12.2-15.4) and 16.8 (13.3-21.4) in arm A and B respectively (HR:1.50, p=0.02). Median OS was 37.7 mos (29.8-41.0) and 44.1 (32.7-not reached) in arm A and B respectively (HR:1.54, p=0.053). Arm A was associated with more toxicity compared to arm B respectively (Grade 3&4 adverse events: 92 versus 71%), with increased early treatment discontinuation before the 3rd cy (14.5 vs 6.2%) & CP dose reduction (12% vs 0%). Pts in Arm A reported inferior RECIST ORR to pre-IDS therapy compared to Arm B (35.1 vs 55.9%). IDS was performed significantly less frequently in arm A (58.1%) vs arm B (76.6%). However among pts who underwent IDS, complete surgical cytoreduction rate (76%) and peri/postoperative complication rate (11.2%) were similar in both arms. Conclusions: The addition of nintedanib to NACT increases toxicity and compromise chemotherapy efficacy leading to a reduced rate of IDS and worse PFS and OS for advanced EOC patient. Clinical trial information: 2011-006288-23.
Adavosertib with chemotherapy (CT) in patients (pts) with platinum-resistant ovarian cancer (PPROC): An open label, four-arm, phase II study.
Authors: Moore Kathleen N. , Chambers Setsuko K. , Hamilton Erika Paige , Chen Lee-may , Oza Amit M. , Ghamande Sharad A. , Konecny Gottfried E. , Plaxe Steven C. , Spitz Daniel Lewis , Geenen Jill J.J. , Troso-Sandoval Tiffany A. , Cragun Janiel M. , Rodrigo Imedio Esteban , Kumar Sanjeev , Mugundu Ganesh M. , Lai Zhongwu , Chmielecki Juliann , Jones Suzanne Fields , Spigel David R. , Cadoo Karen Anne
Published: May 2019

5513

Background: Adavosertib (AZD1775; A), a highly selective WEE1 inhibitor, demonstrated activity and tolerability in combination with carboplatin (C) in primary PROC. This study (NCT02272790) assessed the objective response rate (ORR) and safety of A in PROC. Methods: Pts with recurrent RECIST v1.1 measurable PROC received A with C, gemcitabine (G), weekly paclitaxel (P), or pegylated liposomal doxorubicin (PLD) in 3- (C) or 4-week (G, P, PLD) cycles (Table). Tumor assessments were performed every 2 cycles until disease progression. Primary objective: ORR; other objectives: disease control rate (DCR), progression-free survival (PFS) and safety. Results: In the 94 pts treated (median treatment duration 3 months; range 0–16 months), outcomes were greatest with A (weeks [W]1–3) + C (Table), with ORR of 67% and median PFS (mPFS) of 10.1 months for this cohort. Most common grade ≥3 treatment-emergent adverse events (TEAEs) are shown in the Table, with hematologic toxicity most notable with A (W1–3) + C. TEAEs led to A dose interruptions, reductions and discontinuations in 63%, 30% and 13% of the whole cohort, respectively. A possible positive relationship between CCNE1 amplification and response warrants further investigation. Conclusions: A shows preliminary efficacy when combined with CT. Pts receiving A (W1–3) + C showed greatest benefit. The increased but not unexpected hematologic toxicity is a challenge and could be further studied to optimize the dose schedule and supportive medications. Clinical trial information: NCT02272790. [Table: see text]
Dose-dense early postoperative intraperitoneal chemotherapy in ovarian cancer: Randomized, phase II trial.
Authors: Zang Rongyu , Shi Tingyan , Jiang Rong , Pu Hong , Yang Huijuan , Tu Dongsheng , Dai Zhiyuan , Cai Yulang , Zhang Yuqin , Cheng Xi , Jia Huixun , Tu Ruiqin , Wang Hua-ying , Tang Jie , Luan Yuting , Cai Shumo ,   Shanghai Gynecologic Oncology Group
Published: May 2019

5514

Background: Dose-dense early postoperative intraperitoneal chemo (DD-EPIC) had been carried out in advanced ovarian cancer (OC) pts in China over the past three decades but it was not proved by a prospective study. This trial was designed to confirm the benefit of DD-EPIC in delaying progression and improving survival. Methods: In a multicenter, phase 2 trial, pts with FIGO IIIC-IV OC and optimal debulking surgery (residual disease ≤1cm) were randomly allocated to receive 4 doses of weekly DD-EPIC with cisplatin (50mg/m2) and etoposide (100mg/m2) followed by 6 cycles of intravenous (iv) chemo with carboplatin and taxane every 3 weeks (DD-EPIC group), or standard iv chemo alone (iv group). (ClinicalTrials.gov, NCT01669226). Results: Between 2009 and 2015, 218 pts were randomized, of whom 215 initiated treatment (106 to DD-EPIC and 109 to iv; for efficacy analyses). Totally, 36 pts (16·7%) were received neoadjuvant chemo. With a median of 61·9 mos follow-up, 122 pts died (54 in DD-EPIC and 68 in iv group). Remarkable OS benefit of DD-EPIC was recorded (67·5 mos for DD-EPIC vs. 46·3 mos for iv; HR 0·70, 95% CI 0·49-1·00, P=0·047). Pts in DD-EPIC had a significantly increased median PFS compared with those in iv group (21·7 vs. 16·8 mos; HR 0·64, 95% CI 0·47-0·86, P=0·003). Median TFST was 25·1 vs. 18·0 mos in favor of DD-EPIC (HR 0·62, 95%CI 0·46-0·83, P=0·002). Similar findings were detected in TSST (42·2 vs. 29·3 mos; HR 0·66, 95%CI 0·47-0·94, P=0·019). Grade 3 and 4 Leucopenia (53·8% vs. 35·2%), anemia (23·6% vs. 5·6%) and gastrointestinal events (10·4% vs. 1·9%) were more common in DD-EPIC ( P=0·006, P<0·001 and P=0·010, respectively). Ninety-one pts were detected by gBRCA testing, with 25·3% of cases carrying deleterious BRCAm, but PFS and OS benefit were observed in patients with BRCA-wild type (HR 0·46 and 0·55, 95%CI 0·27-0·81 and 0·27-1·11, respectively). Conclusions: DD-EPIC with a higher completion rate and acceptable treatment burden was associated with longer OS than standard iv alone. Owing to the benefit of relatively long-term OS, DD-EPIC may be considered as a valuable option for OC, particularly in developing countries and BRCA-wild type pts. Clinical trial information: NCT01669226. [Table: see text]
Surveillance in stage I MOGCTs (malignant ovarian germ cell tumors): A MITO prospective study (multicenter Italian trials in ovarian cancer).
Authors: Bergamini Alice , Giorda Giorgio , Ferrandina Gabriella , Cormio Gennaro , Lorusso Domenica , Cassani Chiara , Raspagliesi Francesco , Marinaccio Marco , Bertone Elena , Frigerio Luigi , Scarfone Giovanna , Perrone Myriam , Bocciolone Luca , Savarese Antonella , Pignata Sandro , Mangili Giorgia
Published: May 2019

5516

Background: The standard of treatment of stage I MOGCTs is surgery followed by BEP (bleomycin + etoposide + cisplatin) chemotherapy, except for stage IA dysgerminoma (D) and IAG1 immature teratoma (IT). Surveillance has emerged as a possible option to avoid adjuvant chemotherapy in IB-C1 D, IA-C G2 – G3 IT, and in stage IA mixed and yolk sac tumors (YST), after comprehensive surgical staging (CSS) with negative postoperative markers. The aim of this study was to analyze oncological outcome of stage I MOGCT patients included in the MITO9 study. Methods: MITO9 was a prospective observational study analyzing data collected between 2013 and 2018. 41 patients with stage I conservatively treated MOGCTs were included. Three groups were identified: group A. IA D and IAG1 IT candidate to surveillance according to guidelines; group B. stages IB-C1 D, stage IA-C G2-G3 IT, stage IA mixed and YST were consulted about the option of close surveillance vs adjuvant chemotherapy in case of CSS; group C. all other patients receiving BEP. Results: Median age was 25.6 years (range 14-40). Median follow up was 36,4 months. Group A included 12 patients, 5 IA G1 IT and 7 IA D. Group B included 24 patients. Of these, 2 out of 5 patients (40%) were positive at restaging and were excluded from surveillance protocol. Seven of the 22 remaining patients (31.8%) received chemotherapy, while 15 (68.1%) were enrolled in the surveillance protocol. Out of these 15 patients, 4 were stage IC D (one IC1, one IC2 and two IC3), 2 were mixed stage IA with YST tumor, 9 were G3 IT (four IA, three IC2, one IC3 and one IB). The 7 patients receiving chemotherapy were: 1 dysgerminoma IC2, 2 YST IA, 3 IT G3 (one IA and one IC2) and 1 mixed IA tumour. Group C included 5 patients, three IC YST and two mixed IC2 with YST. Survival of these patients was 100%, while disease free survival was 97.5%. Only one patient in C Group, a stage IA G3 IT treated with adjuvant BEP, relapsed as mature teratoma. None of the patients in the surveillance protocol experienced relapse. Conclusions: These data suggest that close surveillance could be an alternative option to avoid adjuvant chemotherapy in properly staged IB-C1 D, stage IA G2 – G3 IT, stage IA mixed and YST. These findings deserve further confirmation in an international cooperative setting.
A comparison of adjuvant therapy approaches for patients with early-stage uterine serous carcinoma.
Authors: Kurnit Katherine , Pedra Nobre Silvana , Fellman Bryan M. , Iglesias David A , Lindemann Kristina , Eriksson Ane Gerda Zahl , Atasevan Beyhan , Glaser Gretchen Elizabeth , Mueller Jennifer Jean , Soliman Pamela T.
Published: May 2019

5517

Background: Uterine serous carcinoma is a less common subtype of endometrial cancer that is associated with poorer survival. The optimal post-operative adjuvant treatment strategy for these patients remains uncertain. Methods: This multi-institutional, retrospective cohort study evaluated patients with early stage uterine serous carcinoma. Patients with FIGO Stage IA-II disease after surgery, whose tumors had serous or mixed serous/non-serous histology were included. Patients with carcinosarcoma were excluded. Clinical data were abstracted from local medical records. Summary statistics, Fisher’s exact, and Kruskal-Wallis tests were used to analyze demographic and clinical characteristics. Univariable and multivariable analyses were performed for recurrence-free survival (RFS) and overall survival (OS). Results: 634 patients were included. 77% of patients had Stage IA disease, 42% showed no myometrial invasion. The majority had pure serous histology (72%) and LVSI (76%). Adjuvant treatment varied: 12% received no adjuvant therapy, 7% had chemotherapy alone, 51% had cuff brachytherapy, 12% had cuff brachytherapy with chemotherapy (cuff/chemo), and 19% underwent pelvic radiation (EBRT). Complete RFS and OS data were available for 607 and 609 patients, respectively, and the median follow-up time was 58 months. As compared with patients who received no adjuvant therapy, patients who received cuff or cuff/chemo had improved RFS (cuff: HR 0.70, p = 0.02; cuff/chemo HR 0.53, p = 0.01) and OS (cuff HR 0.56, p = 0.001; cuff/chemo HR 0.48, p = 0.01). In a direct comparison, patients with cuff/chemo had better RFS and OS than those with chemotherapy alone (RFS HR 0.52, p = 0.03; OS HR 0.50, p = 0.05). There were no differences in RFS or OS for women who received chemotherapy alone or EBRT. Improved survival with cuff and cuff/chemo persisted on multivariable analyses (included age, stage, LVSI, adjuvant therapy type); additionally, EBRT was also associated with improved OS. In analyses limited to patients without myometrial invasion, patients with cuff or cuff/chemo had improved RFS and OS compared with observation alone. Conclusions: The use of adjuvant cuff brachytherapy with and without chemotherapy was associated with improved RFS and OS in patients with early stage uterine serous carcinoma.
Exploratory analysis of the effect of maintenance rucaparib on postprogression outcomes in patients (pts) with platinum-sensitive recurrent ovarian carcinoma (OC) and updated safety data from the phase 3 study ARIEL3.
Authors: Coleman Robert L. , Oza Amit M. , Lorusso Domenica , Aghajanian Carol , Oaknin Ana , Dean Andrew Peter , Colombo Nicoletta , Weberpals Johanne I , Clamp Andrew R. , Scambia Giovanni , Leary Alexandra , Holloway Robert W. , Amenedo Margarita , Fong Peter C.C. , Goh Jeffrey C. , O'Malley David M. , Cameron Teresa , Maloney Lara , Goble Sandra , Ledermann Jonathan A.
Published: May 2019

5522

Background: In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo in all predefined, nested cohorts: BRCA mutation; BRCA mutation + wild-type BRCA/high loss of heterozygosity (LOH); and intent-to-treat (ITT) population. Methods: Pts were randomized 2:1 to receive oral rucaparib 600 mg BID or placebo. Exploratory endpoints of time to first subsequent therapy (TFST), time to investigator-assessed PFS on the subsequent line of treatment or death (PFS2), and time to second subsequent therapy (TSST) were assessed in the predefined cohorts. Results: Exploratory efficacy endpoint data are given in the Table. As of Dec 31, 2017, the most common treatment-emergent adverse events (TEAEs) of any grade (rucaparib vs placebo) were nausea (75.8% vs 36.5%), asthenia/fatigue (70.7% vs 44.4%), dysgeusia (39.8% vs 6.9%), and anemia/decreased hemoglobin (39.0% vs 5.3%). The most common grade ≥3 TEAEs were anemia/decreased hemoglobin (21.5% vs 0.5%) and alanine/aspartate aminotransferase increase (10.2% vs 0.0%). Conclusions: Rucaparib significantly improved the clinically meaningful endpoints TFST, PFS2, and TSST vs placebo in all predefined cohorts of pts with platinum-sensitive, recurrent OC. The updated safety profile was consistent with prior reports. Clinical trial information: NCT01968213. [Table: see text]
A phase I study of veliparib incorporated into front-line platinum based cheotherpy and bevacizumab in epithelial ovarian cancer (NCT00989651): A GOG/nrg trial.
Authors: Armstrong Deborah Kay , Moore Kathleen N. , Miller Austin , Bell-McGuinn Katherine M. , Schilder Russell J. , Fracasso Paula M. , Walker Joan L. , Duska Linda R. , Mathews Cara Amanda , Chen Alice P. , O'Malley David M. , Gray Heidi J. , O'Cearbhaill Roisin Eilish , Guntupalli Saketh R , Hagemann Andrea R. , Aghajanian Carol
Published: May 2019

5523

Background: Veliparib, a poly-(ADP-ribose)-polymerase inhibitor, increases anti-tumor activity when combined with platinum chemotherapy and has monotherapy activity in BRCA deficient tumors. This study was done to determine the recommended phase II dose (RP2D) of veliparib in combination with front line treatment for epithelial ovarian cancer (EOC). Methods: Eligible patients had newly diagnosed, stage II-IV EOC. Six regimens were evaluated, 3 variations of chemo delivery with either continuous (D1-21) or intermittent (days-2-5) veliparib BID. Chemo included 1: IV q3week carboplatin (C) (AUC 6) and paclitaxel(T) (175mg/m2); 2, IV q3week C (AUC 6) and weekly T(80mg/m2); and 3, IV T (135mg/m2, day 1), IP cisplatin (75mg/m2, day 1 or 2) and IP T (60mg/m2, day 8). Bevacizumab 15mg/kg started cycle 2 and continued as monotherapy cycles 7-22. A 3+3 dose escalation design evaluated dose-limiting toxicities (DLTs) in cycles 1 and 2. Once < 2/6 patients experienced a DLT, that dose level was expanded to evaluate feasibility over 4 cycles. Results: The study accrued 424 treated patients. For regimen 1, continuous (Reg1c) the maximum tolerated dose (MTD) was 250mg veliparib BID but the feasible dose was found to be 150mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250mg BID respectively. For Reg2c the MTD and feasible dose were the same at 150mg BID. For Reg2i the MTD and feasible dose were 250 and 150mg BID respectively. For Reg3c the MTD and feasible dose are both 150mg BID and for Reg3i, the MTD was 400mg BID and the feasible dose felt to be 300mg BID. Median PFS by residual disease and BRCA status is: (Positive residual disease) 14.6, 19.1 and 16.9 months for BRCA+, BRCAwt and BRCA ukn respectively. For no gross residual disease the PFS is NR, 34.2 and 24.5 months respectively. Conclusions: Given the difficulty with toxicity not defined as a DLT, the RP2D for all regimens is veliparib 150mg BID. This data informed the dose that moved into the phase III trial GOG 3005/Velia: NCT02470585. Velia also incorporated maintenance veliparib instead of maintenance bevacizumab among all high grade serous patients (BRCA+ and wt). These results will determine utilization of veliparib in this space. Clinical trial information: NCT00989651.
Human papillomavirus genotype and prognosis of invasive cervical cancer: A nationwide cohort study.
Authors: Lei Jiayao , Ploner Alexander , Lagheden Camilla , Eklund Carina , Nordqvist Kleppe Sara , Andrae Bengt , Elfström Klara Miriam , Dillner Joakim , Sparén Pär , Sundström Karin
Published: May 2019

5525

Background: The role of human papillomavirus (HPV) in development from oncogenic infection to invasive cervical cancer (ICC) has been well established. However, the association of HPV genotypes and prognosis of ICC is controversial. Methods: We identified all ICC diagnosed in Sweden during the years 2002-2011 (4254 confirmed cases after clinical and histo-pathological review), requested all archival formalin-fixed, paraffin-embedded blocks and subjected them to comprehensive HPV genotyping. Twenty out of twenty-five archives agreed to the study, contributing a total of 2845 confirmed cases with valid HPV results. Cases were followed up from date of cancer diagnosis to 31 December, 2015, migration from Sweden, or death; whichever occurred first. Five-year relative survival ratios (RSRs) were calculated and excess hazard ratios (EHRs) with 95% confidence intervals (CIs) were estimated using Poisson regression. Results: HPV was detected in 2365 tumors (83.1% of all cases). The five-year RSR by tumor HPV status was 0.54 (HPV negative), 0.76 (HPV16 positive), 0.73 (HPV18 positive), 0.72 (other high-risk HPV positive) and 0.56 (low-risk HPV positive) compared to the age-matched general female population. Compared to cases with HPV-negative tumor, a significantly lower excess mortality was seen if the tumor was positive for HPV16 (EHR:0.54, 95% CI 0.44-0.65), other high-risk HPV (EHR:0.47, 95% CI 0.37-0.60), and low-risk HPV (EHR:0.48, 95% CI 0.32-0.74), after adjustment for age, time since cancer diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, educational level and histology. However, the mortality among women with HPV18 positive tumors were not statistically significantly different from cases with HPV-negative tumors. In women with a single HPV infection of either HPV16 or HPV18, those with HPV18-positive tumors had 56% (EHR:1.56, 95% CI: 1.13-1.97) higher excess mortality compared to women with HPV16-positive tumors. Conclusions: HPV genotype in cervical cancer tumor is associated with prognosis of ICC. Single HPV18 positivity indicated a poorer prognosis than single HPV16 positivity. This could add information of value beyond the established clinical prognostic factors for women diagnosed with ICC.
Prognostic significance of the number of pelvic lymph-nodes resection in patients with cervical adenocarcinoma: An analysis from JGOG 1070S study.
Authors: Ikeda Yuji , Kita Tsunekazu , Furusawa Akiko , Takekuma Munetaka , Mikami Mikio
Published: May 2019

5529

Background: Although resection of more than 20 lymph-nodes is considered to be adequate in pelvic lymphadenectomy for cervical cancer patients, prognostic significance of the number of resected lymph-nodes (PLN-num) is clinically still unknown. Methods: This nationwide multicenter retrospective study (JGOG 1070S) examined consecutive 693 patients with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy including pelvic and/or para-aortic lymphadenectomy between 2008-2009 at 87 institutions of the Japanese Gynecologic Oncology Group. Maximum number of enrollments from one institution was limited 10 or less to minimize the inter-institutional bias. Correlation between PLN-num and prognosis was analyzed using Cox hazard model with considering histological subtypes. Results: Of 473 eligible cases in this study, the average PLN-num per a case in each institution was positively correlated with the number of total cases treated in each institution per year. (R = 0.42, P = 0.012). Patients with high PLN-num showed favorable progression free survival (PFS) (P = 0.12). Focusing on adeno and adeno-squamous carcinomas, significantly improved PFS was shown in high PLN-num cases (P = 0.012), although no significance was found in squamous cell carcinoma (P = 0.754). Multivariate analysis in adeno and adeno-squamous cases showed PLN-num as an independent prognostic factor (HR; 0.46, 95%CI; 0.24–0.84, P = 0.026) along with disease stage and adjuvant therapeutics. Subset analysis of adeno and adeno-squamous cases without adjuvant therapeutics showed significant improvement of survival in high PLN-num group (P = 0.019). Conclusions: In our study, PLN-num in lymphadenectomy for patients with cervical adeno or adeno-squamous carcinoma was clarified to be a significant prognostic factor. Systematic total lymphadenectomy is recommended for these patients to obtain a favorable prognosis.
Cervical cancer harboring a Rb1 mutation may sensitize to cisplatin via PI3K/AKT pathway by regulating apoptosis.
Authors: Luo Peng , Zou Jingwen , Bu Junguo , Meng Hui , Chen Jie , Zhang Jian
Published: May 2019

5531

Background: Cervical cancer is one of the most common malignant tumors in women and major causes of cancer death in women. Although concurrent chemoradiotherapy has improved the treatment of cervical cancer, due to the heterogeneity of the tumor to chemotherapy or radiation therapy, especially the varied response to chemotherapy, the patients respond differently to the same therapeutic regimen, furthermore some patients get rapid progression. Therefore, we attempted to analyze the potential relationship between genomic mutation and chemotherapy response and survival in cervical cancer patients. Methods: Clinical information and sequencing data of Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) in Genomic Data Commons (GDC) data portal were obtained through TCGAbiolinks. Only patients with stage IIB-IV CESC who received cisplatin only and were included. Cisplatin sensitivity data and sequencing data of CESC cell lines were obtained from the Genomics of Drug Sensitivity in Cancer (GDSC). Cox regression analysis, Kaplan-Meier survival analysis, differential analysis of gene expression and functional enrichment were used to explore the role of different mutations in survival and cisplatin sensitivity. Results: A total of 48 patients with stage IIB-IV CESC were enrolled. 77 genes with mutation frequency > 10% were included in final analysis . Multivariate analysis showed that the mutation of Rb1 was an independent predictor of overall survival (OS) (HR = 0.07, 95%CI 0.01-0.73, P = 0.026). Patients with mutant Rb1 had better overall survival (134.2 versus 86.8 months) compared with patients with wild-type Rb1. The half maximal inhibitory concentration (IC50) of the mutant Rb1 cell line to cisplatin was significantly lower than that of the wild-type cell line (3.49 versus 10.15μM, P = 0.038). A total of 332 differently expressed genes (DEGs) were identified and the KEGG pathway enrichment analysis showed that most DEGs were enriched in the PI3K/AKT pathway (P = 0.015). Conclusions: We found that Rb1 mutation was an independent survival predictor in stage IIB-IV CESC, and CESC patients with Rb1 mutation may be more sensitive to cisplatin.
Efficacy and safety of tivozanib in recurrent, platinum-resistant ovarian, fallopian tube or primary peritoneal cancer.
Authors: Swetzig Wendy M , Lurain John Robert , Berry Emily , Pineda Mario Javier , Shahabi Shohreh , Perry LaToya , Neubauer Nikki Lynn , Nieves-Neira Wilberto , Schink Julian C. , Schiller Alissa , Novak Karen , Anderson Nancy Jean , Burdett Kirsten Bell , Strohl Anna Everett , Kocherginsky Masha , Matei Daniela
Published: May 2019

5538

Background: Tivozanib is a potent, selective pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor with a long half-life. This study assessed its activity in patients with recurrent, platinum-resistant ovarian cancer (OC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC). Methods: This open-label phase II study used a Simon’s two-stage design. Eligible patients had recurrent, platinum-resistant OC, FTC or PPC; ECOG PS of 0-1; normal end organ function; and measurable or detectable disease. There was no limit on the number of prior regimens. Treatment consisted of tivozanib 1.5 mg orally once daily (3 weeks on/1 week off). The primary endpoint was response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity assessment. If 1 partial response (PR) was observed in stage I [n = 12], enrollment proceeded to stage II. The null hypothesis was rejected for ≥ 4 responses in 30 patients. Results: Thirty-one patients were enrolled, and 30 were treated. Twenty-three had OC [76.67%], 5 FTC [16.67%] and 2 PPC [6.67%]. Twenty-six had measurable [86.67%] and 4 detectable disease [13.37%]. The median age was 60, and median number of prior regimens was 4 [range 1-9]. Four PRs [13.33%] were recorded. Twelve patients had stable disease (SD) [40%]. The clinical benefit rate (PR + SD) was 53%. Seven patients [23.33%] survived progression-free for > 6 mos. One patient continued treatment for > 2 yrs. The median PFS was 4 mos [range 1-25] and median OS was 8 mos [range 1-39]. There were no treatment-related deaths. Grade 3-4 related toxicities were hypertension [8], fatigue [3], fistula [2], hyponatremia [2], intestinal perforation, obstruction, stroke, proteinuria, hypomagnesemia, hypoalbuminemia, portal hypertension, nausea and anemia [1 each]. Frequent grade 1-2 related toxicities included fatigue [19], hypertension [13], anorexia [12], arthralgia [11], diarrhea [11], weight loss [10], hoarseness [8], headache [8] and nausea [7]. Exploratory analyses in tumor samples are ongoing. Conclusions: Tivozanib is active in patients with recurrent OC, FTC or PPC, without substantial toxicity, supporting its further development. Clinical trial information: NCT01853644.
Genomics of HER2+ breast cancer in young women before and after exposure to chemotherapy (chemo) plus trastuzumab (H).
Authors: Waks Adrienne Gropper , Jain Esha , Collins Laura C. , Rosenberg Shoshana M. , Ruddy Kathryn Jean , Tamimi Rulla M , Schapira Lidia , Come Steven E. , Peppercorn Jeffrey M. , Borges Virginia F. , Warner Ellen , Snow Craig , Partridge Ann H. , Wagle Nikhil
Published: May 2019

554

Background: HER2+ breast cancer (BC) is particularly common in young women. Genomic features of HER2+ tumors before and after H-based therapy have not been described in a population of young women and may point to clinically targetable mechanisms of resistance. Methods: From a large prospective cohort of women diagnosed with BC age ≤40 years, we identified those with HER2+ BC and tumor tissue available for sequencing before and after chemo+H. Whole exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. Evolutionary analysis was performed for patients with both pre- and post-treatment (tx) samples. Results: 22 women had successful WES samples from at least one timepoint; 13 of these had paired sequencing results both before and after chemo+H. For the majority of women, post-tx sample was following neoadjuvant chemo + H, though post-tx timepoint for other women represented locoregional or distant metastasis (Table). TP53 was the only gene that was significantly recurrently mutated in both pre- and post-tx samples. Comparison of matched pre-tx and post-tx samples demonstrated that large changes in HER2 CN over the course of tx were uncommon, only 2/13 pts had > 2-fold change in HER2 CN. Other clonal and subclonal genomic alterations were found to be acquired in the post-tx sample compared to the pre-tx sample. One patient acquired a putative activating mutation in ERBB2. Another patient acquired a clonal hotpsot mutation in TP53. MYC gene amplification was observed in 4 post-tx tumors. NOTCH2 alterations were found in post-tx biopsies from 2 different patients, and mutations in STIL were also found in post-tx biopsies from 2 patients, though the function of these mutations is not known. Conclusions: HER2+ breast tumors in young women display genomic evolution following tx with chemo+H. HER2 CN changes are uncommon, but we identified several genes that warrant exploration as potential mechanisms of resistance to therapy in this population.[Table: see text]
Results of the VENUS study: Bevacizumab efficacy and safety in platinum-sensitive recurrent ovarian cancer (OC)—A real-life ambispective study.
Authors: Ray-Coquard Isabelle Laure , Alexandre Jerome , Goldwasser Francois , Spano Jean-Philippe , Berton-Rigaud Dominique , Savoye Aude-Marie , Fabbro Michel , Bazan Fernando , Kalbacher Elsa , Raban Nadia , Giraud Claire , Pottier Virginie , Selle Frédéric , Patsouris Anne , Garnier-Tixidre Claire , Mercier Blas Anne , Provencal Jocelyne , Brocard Fabien , Berdougo-Tritz Jessica , Launay-Vacher Vincent ,   VENUS Study Group
Published: May 2019

5540

Background: The VENUS study reports on the efficacy/safety of bevacizumab (Bev) in patients (pts) treated in the real-life setting. Methods: In this multicentric observational ambispective VENUS study, all Pts were naive of any antiVEGF and received Bev +/- chemotherapy. Pts were followed until progression or death, for a maximum of 3 years since Bev initiation. De novo side effects were defined as symptoms for which patients were naïve at baseline. Results: 148 OC pts were included (27 centres), 10 excluded and 8 were lost of follow-up. 52 were retrospective. Median age 64 years (55-70). 84.1% were advanced. Median duration of Bev was 8.6 months, min 1 max 36 months. Initial Bev dose was 15 mg/kg Q3W for 65.3%, 10.0 for 22.5%, 7.5 for 10.2% and 5.0 for 2%. 2 pts presented with thrombotic micro-angiopathy (1.4%). Before Bev, hypertension (HTN) was present in 28.9%; proteinuria in 11.3%. Incidence of de novo HTN was 25%. 43 pts (31.2%) experienced de novo Grade 1-2 Pu, for a total of 56 events, no grade 3-4 was observed. A total of 12 Grade 4 events occurred: 9 neutropenia and 3 thrombopenia. Mean overall survival (OS) and progression free survival (PFS) were 30.0 and 13.3 months, respectively. Conclusions: 1) 1/3 of pts were treated at low doses in this real-life study; 2) safety of Bev in real-life was manageable and as expected, 3) OS and PFS were consistent with those reported in the OCEANS study: PFS 12.4 and OS 33.6 months but lower than in the GOG-0213 study: PFS 13.8 and OS 42.6 months. De novo events recorded during follow-up. [Table: see text]
SOLO1 versus SOLO2: Cost-effectiveness of olaparib as maintenance therapy for newly diagnosed and platinum-sensitive recurrent ovarian carcinoma among women with germline BRCA mutations (gBRCAmut).
Authors: Wolford Juliet Elizabeth , Tewari Krishnansu Sujata , Liang Su-Ying , Bai Jiaru , Mann Amandeep Kaur , Moore Kathleen N. , Pujade-Lauraine Eric , Ledermann Jonathan A. , Monk Bradley J. , Chan John K.
Published: May 2019

5545

Background: With the December 19, 2018 regulatory approval by the US FDA of olaparib tablets as maintenance therapy for women with deleterious or suspected deleterious germline or somatic BRCAmut advanced ovarian carcinoma, it becomes important to clarify the role of PARP inhibitors in this disease. We evaluated cost-effectiveness of olaparib in the upfront (SOLO1) versus the recurrent maintenance setting (SOLO2). Methods: Data were obtained from SOLO1, the phase 3 placebo-controlled randomized upfront maintenance study among gBRCAmut patients [median PFS greater than 49.8 vs 13.8m: HR 0.30; 95% CI, 0.23-0.41; p < 0.001, NCT01844986] and SOLO2, the phase 3 placebo-controlled randomized maintenance study among gBRCAmut patients with platinum-sensitive recurrence and at least two prior lines of therapy [median PFS 19.1 vs 5.5m: HR 0.30; 95% CI, 0.22-0.41; p < 0.0001, NCT01874353]. Investigator-assessed median PFS and toxicity data from the trials were incorporated in a Markov model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2015, the costs of pre-treatment testing (eg. gBRCAmut), medications, and management of adverse effects were analyzed. Incremental cost-effectiveness ratios (ICERs) per month of life gained and individual PFS-life year saved (PFS-LYS) were also calculated and compared. Results: In SOLO1, cost prior to progression was 1.7x that of SOLO2 ($937,440 vs $564,451). With the extended, estimated median PFS of at least 49.8m for SOLO1 and 19.1m for SOLO2, upfront maintenance therapy was more cost-effective. SOLO 1 was associated with $312,480 PF-LYS per individual patient, while SOLO2 demonstrated $498,045 PF-LYS. Maintenance olaparib was found to be more cost-effective in the 1st-line setting, with an ICER of $12,149 per month of life gained when compared directly to SOLO2. Conclusions: Although the higher cost associated with olaparib in SOLO1 reflects the longer time patients stay on drug due to extended PFS, the ICER supports early use in the disease course as first-line maintenance therapy among women with gBRCAmut advanced ovarian carcinoma.