LION (Phase III Trial): Lymphadenectomy for LN-Negative Advanced Ovarian Cancer Following Complete Resection CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals LN, lymph node. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

Lymphadenectomy in Resected, LN-Negative Advanced Ovarian Cancer: Background In pts with advanced ovarian cancer Upfront surgery achieving macroscopic complete resection part of current standard of care[1] Randomized trial of systematic pelvic and para-aortic LNE demonstrated significant improvement in PFS, but not OS, in pts with little to no residual disease[2] Retrospective analysis of phase III data suggested potential OS benefit of LNE in pts without gross residual disease[3] Current prospective, randomized phase III trial investigated PFS and OS benefits of LNE in pts with LN-negative advanced ovarian cancer following macroscopic complete resection[4] LN, lymph node; LNE, lymphadenectomy. 1. Goff BA. J Gynecol Oncol. 2013;24:83-91. 2. Panici PB, et al. J Natl Cancer Inst. 2005;97:560-566. 3. du Bois A, et al. J Clin Oncol. 2010;28:1733-1739. 4. Harter P, et al. ASCO 2017. Abstract 5500. Slide credit: clinicaloptions.com

LION: Study Design Multicenter, prospective, randomized, open-label phase III trial All centers required to demonstrate surgical skill prior to participation Primary endpoint: OS Secondary endpoints: PFS, QoL, number of resected LN Stratified by center, age, ECOG PS Adult pts with suspected or proven FIGO stage IIB-IV epithelial ovarian cancer, macroscopic complete resection, ECOG PS 0/1, and clinically/ radiologically negative pelvic and para-aortic LN; no prior CT or LN dissection (N = 647) Lymphadenectomy (n = 323) No lymphadenectomy (n = 324) CT, chemotherapy; ECOG, Eastern Cooperative Oncology Group; FIGO, International Federation of Gynecology and Obstetrics; LN, lymph node; PS, performance status; QoL, quality of life. Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

LION: Baseline Characteristics LNE (n = 323) No LNE (n = 324) Median age, yrs (range) 60 (21-83) 60 (23-78) ECOG PS, n (%) 1 272 (84.2) 51 (15.8) 280 (86.4) 44 (13.6) Histologic diagnosis, n (%) Before registration Ovarian, fallopian tube, peritoneal Other 106 (32.8) 304 (94.1) 19 (5.9) 106 (32.7) 303 (93.5) 21 (6.5) Median pre-op CA 125, U/mL (IQR) 416 (138-1276) 347 (122-1025) Characteristic, n (%) LNE (n = 323) No LNE (n = 324) Final FIGO stage I-IIA IIB-IIIA III-IV Missing 15 (4.6) 41 (12.7) 261 (80.8) 6 (1.9) 17 (5.2) 52 (16.0) 244 (75.3) 11 (3.4) Histology Grade 2/3 serous Other 234 (72.4) 89 (27.6) 227 (70.1) 97 (29.9) ECOG, Eastern Cooperative Oncology Group; FIGO, International Federation of Gynecology and Obstetrics; IQR, interquartile range; LNE, lymphadenectomy; PS, performance status. Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

LION: Characteristics of Surgery Characteristic, n (%) LNE (n = 323) No LNE (n = 324) Bilateral salpingo-oophorectomy* 319 (98.8) 320 (98.8) Hysterectomy* 321 (99.4) 322 (99.4) Omentectomy (Partial) peritonectomy Pelvis Paracolic Diaphragm 291 (90.1) 276 (85.5) 193 (59.8) 173 (53.6) 291 (89.8) 278 (85.8) 208 (64.2) 196 (60.5) Characteristic, n (%) LNE (n = 323) No LNE (n = 324) GI tract resection Stoma 169 (52.3) 34 (10.5) 167 (51.5) 24 (7.4) Splenectomy 62 (19.2) 56 (17.3) Porta hepatis/lesser omentum 61 (18.9) 69 (21.3) Partial pancreatectomy 7 (2.1) Partial hepatectomy 27 (8.4) 28 (8.6) Pleurectomy 20 (6.2) Complete resection 321 (99.4) 322 (99.4) GI, gastrointestinal; LNE, lymphadenectomy *Includes procedures performed earlier. Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

LION: Efficacy and QoL Outcomes All Pts (N = 647) Median OS, mos (95% CI) 5-yr OS, % 67.2 (61.2-74.8) 55.9 Median PFS, mos (95% CI) 25.5 (21.9-28.6) Outcome, Mos LNE (n = 323) No LNE (n = 324) HR (95% CI) P Value Median OS 65.5 69.2 1.057 (0.833-1.341) .65 Median PFS 25.5 1.106 (0.915-1.338) LNE, lymphadenectomy; QoL, quality of life. No difference in QoL between arms at baseline, discharge, end of chemotherapy, or 6 mos post chemotherapy Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

LION: Intraoperative Outcomes LNE (n = 323) No LNE (n = 324) Difference P Value Study procedure per randomization, n (%) 320 (99.1) 313 (96.6) Median total resected LN (IQR) Para-aortic Pelvic 57 (45-73) 22 (16-33) 35 (26-43) LN metastases, n (%) 180 (55.7) Median surgery duration, min (IQR) 340 (270-420) 280 (210-360) + 1 hour < .001 Median blood loss, mL (IQR) 650 (400-1000) 500 (300-900) + 150 mL Transfusions, n (%) Massive (> 10 RBC/24 hrs) 205 (63.7) 7 (2.2) 181 (56.0) 2 (0.6) + 8% .005 .09 Fresh-frozen plasma, n (%) 117 (36.3) 96 (29.7) + 7% .07 Intermediate/intensive care unit, n (%) 250 (77.6) 223 (69.4) .01 IQR, interquartile range; LN, lymph node; LNE, lymphadenectomy; RBC, red blood cell. Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

LION: Postoperative Outcomes Outcome, n (%) LNE (n = 323) No LNE (n = 324) P Value Infections requiring antibiotics 83 (25.8) 60 (18.6) .03 Asymptomatic lymph cysts 14 (4.4) 1 (0.3) < .001 Symptomatic lymph cysts 10 (3.1) .001 Readmission 40 (12.4) 27 (8.3) .09 Relaparotomy for complications 21 (6.5) .01 60-day post-op mortality 3 (0.9) .049 Platinum/taxane chemotherapy 257 (79.6) 274 (84.6) IQR, interquartile range; LNE, lymphadenectomy No statistically significant difference between arms in rates of fever, sepsis, thrombosis, pulmonary embolism, secondary wound healing, prolonged ileus, peripheral sensory/motor neurologic events, fistula Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

LION: Conclusions In pts with advanced ovarian cancer, intra-abdominal complete resection, and clinically/radiologically negative lymph nodes: Median OS: 67.2 mos; 5-yr OS: 55.9%; median PFS: 25.5 mos Systemic pelvic and para-aortic LNE Did not improve OS or PFS despite removal of subclinical LN metastases in 56% of pts Significantly increased postoperative morbidity and mortality Investigators conclude that systematic LNE not recommended in this pt population LN, lymph node; LNE, lymphadenectomy. Slide credit: clinicaloptions.com Harter P, et al. ASCO 2017. Abstract 5500.

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