P2124 - Effectiveness of Gemcitabine Plus S-1 Combination as First-Line Therapy Tested in Japanese Population for Advanced Biliary Tract Cancer: Systematic Review of Clinical Trials

Tuesday, October 26, 2021

10:30 AM – 4:00 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

Ammu Susheela, MD

Loyala Medicine/MacNeal Hospital
Berwyn, IL, United States

Faiza Ahmed, MD, MS, BSc¹, Ujala Nasr, MD², Ammu Susheela, MD³, Faiza Zakaria, MD², Sundus Ali, MD⁴, Alaa Hamdan, MD¹, Anusha Sajja, MD¹, Kim Andrews, MD, PhD, MHA⁵, Sai Harsha Bobba, MD⁶, Shanthi Potla, MD⁷, Aysha Aslam, MD⁸, Marc-Darlene Mezidor, MD⁹, Zeynep Yukselen, MD¹, Karthik Mohan, DO¹, Raza Zarrar, MD¹⁰, Endrit Shahini, MSc, MD¹¹, Thiruvengadam Muniraj, MD, PhD, MRCP¹²
¹Larkin Community Hospital, South Miami, FL; ²Dow Medical College, Karachi, Sindh, Pakistan; ³Loyala Medicine/MacNeal Hospital, Berwyn, IL; ⁴Ascension St. Agnes Hospital, Baltimore, MD; ⁵Prince Mohammad Bin Fahad University, Al Khobar, Ar Riyad, Saudi Arabia; ⁶Swedish Hospital, Chicago, IL; ⁷Beckley ARH Hospital, Beckley, WV; ⁸Louis A Weiss Memorial Hospital, Chicago, IL; ⁹AMITA Health Saint Joseph Hospital, Evanston, IL; ¹⁰Mayo Clinic, Rochester, MN; ¹¹National Institute of Research-Saverio De Bellis, Bari, Basilicata, Italy; ¹²Yale New Haven Health System-Yale Center for Pancreatitis, New Haven, CT

Introduction: Biliary tract cancers (BTC) are uncommon but highly lethal cancers in most parts of the world but is a common cause of mortality in Asia. In Japan, BTC is the sixth leading cause of cancer-related death, and the occurrence is about 10 for every 100,000 people. The standard of care first-line chemotherapy treatment recommended in Japan for patients with advanced BTC is the combination of gemcitabine and cisplatin (GC). In recent decade, trials have been conducted to evaluate gemcitabine and s-1 (GS) combination as the first-line chemotherapy. Here, we present the first systematic review of GS efficacy profile in advanced BTC patients.

Methods: A comprehensive search was performed using multiple databases from inception - April 2021 using the PICO framework and PRISMA guidelines.

Results: A total of six studies (n=217) met the inclusion criteria. All studies are phase II clinical trials that were performed in Japan. There were higher number of males than females enrolled in each trial (sum=125 vs. 92). All trials achieved a median survival time (MST) of 15.9 mon(95% CI,8.9-23.0);vs. 9.0mon(95 %CI,4.0–13.9); vs 8.9mon; vs. 12.5mon(95% CI, 9.0–15.4); vs. 12.7mon(95% CI, 8.4–23.5); vs. 11.6mon (95% CI, 7.3–15.6) and a 1-year survival rate of 44.7 %(95 %CI 29.0–61.5); vs. 52.9%; vs. 52.0%(95% CI, 31.2–69.2%),p=0.02; vs. 44.4%, respectively. The location of primary tumor was classified as intrahepatic, extrahepatic, gallbladder, or ampulla of vater. Five studies reported partial response [5 (13.2%), 6, 6(20%), 7(30.4%), 10(29%)] , overall response rate [15.8%; (20.6% vs. 18.4%); 20%, 30.4%, 34.3%], overall disease control rate [(68.4%, (76.5% vs. 68.4%), 21(70%), 87%, 82.9%)], and stable disease [20(52.6%),19, 15 (50%), 13(56.5%), 17(49%)], respectively. Progressive disease data [(16(15.8%) vs. 8 vs. 8(26.7%)] was provided by Arima et al 2017 , Kim et al 2014, and Sasaki et al 2013. Median time-to-progression was similar in all reported trials [5.8 months (95% CI, 3.1-8.5); vs. 5.6 months; vs. 5.9 months(95% CI, 4.0–7.7)]. For additional information, refer to Table 1.

Discussion: The combination of GS chemotherapy exhibited promising antitumor activity for improving survival in Japanese patients with advanced BTC. Further comparative clinical trials between GS and GC are warranted to confirm the superiority of GS treatment in such patients. Additionally, large long-term clinical trials should be conducted in Western countries population to evaluate GS efficacy in gradually increasing BTC cases.

	*Arima et al 2017*	*Kim et al 2015*	*Sasaki et al 2013*	*Morizane et al 2013*	*Kanai et al 2011*	*Sasaki et al 2010*
Country	Japan	Japan	Japan	Japan	Japan	Japan
Treatment	Gemcitabine: IV, 1,000 mg/m2 over 30 min on days 1, 8, S-1: oral, 60/80/100 mg/day based on the BSA, twice daily, day1-14 (treatment repeated every 3 weeks)	Gemcitabine: IV, 1,000 mg/m2 over 30 min, days 1, 8 S-1: oral, 40 mg/m2, twice daily, days 1–14 (treatment repeated every 3 weeks)	Gemcitabine: IV, 1,000 mg/m2 over 30 min on days 1,15; repeated every 4 weeks. S-1: oral, 40 mg/m2 b.i.d., twice daily, on days 1–14, followed by 2-week rest.	Gemcitabine: IV, 1000 mg⁄m2, day 1, 8 S-1: oral, 60 mg⁄m2, twice daily, days 1–14 (treatment repeated every 3 weeks)	Gemcitabine: IV, 1,000 mg/m2 over 30 min on days 1, 8 S-1: oral, daily 60 mg/m2 on days 1–14. (treatment repeated every 3 weeks)	Gemcitabine: IV, 1,000 mg/m2 over 30 min on day 1,15; repeated every 4 weeks. S-1: oral,40 mg/m2 b.i.d., twice daily, days 1–14, followed by 2-week rest.
Sample Size	38	38	62 (GS=30; Gem alone=32)	101 (GS=51;s-1 alone=50)	25	35
Male/Female (%)	19(50%) / 19(50%)	23(60.5%) / 15(39.5%)	16(53%) / 14(47%)	27 / 24	18(72%) / 7 (28%)	22(63%) /13(37%)
Median age (range)	66 (44-81)	60.5 (44-71)	68 (47-83)	66 (30-78)	63 ( 32-78)	67 (49-79)
ECOG performance status	0=31(82%); 1=6(16%); 2=1(2%)	0=23(60.5%); 1=15(39.5%)	0=18(60%); 1=11(37%); 2=1(3%); p=1.00	0=39 (76.5%); 1=12 (23.5%)	NA	0=16(46%); 1=18(51%); 2=1(3%)
Location of the primary tumor	Intrahepatic: 12(37%) Extrahepatic: 14(31%) Gallbladder: 9(24%) Ampulla of Vater: 3(8%)	Intrahepatic: 2(5.3%) Extrahepatic: 21(55.2%) Gallbladder: 12 (31.6%) Ampulla of Vater: 3(7.9%)	Intrahepatic: 8(27%) Extrahepatic: 6(20%) Gallbladder: 16(53%)	Intrahepatic: 20 (39.2%) Extrahepatic: 9 (17.6%) Gallbladder: 19(37.3%) Ampulla of Vater: 3 (5.9%)	Intrahepatic: 5(20%) Extrahepatic: 11(44%) Gallbladder: 8(32%) Ampulla of vetor: 1(4%)	Intrahepatic: 14(40%) Extrahepatic: 6(17%) Gallbladder: 14(40%) Ampulla of vetor: 1(3%)
Disease Status	NA	NA	Locally advanced: 7(23%); Metastatic: 20(67%); Recurrent: 3(10%); P=1.00	Locally advanced: 8(15.7%); Metastatic: 29(56.9%); Recurrent: 14(27.5%)	unresectable: 21(84.0%); Recurrent: 4(16.0%)	Locally advanced: 3(9%); Metastatic: 25(71%); Recurrent: 7(20%)
Median Carcinoembryonic antigen (CEA ) ng/ml (range)	NA	NA	6.7(1.8-3,540);p=0.14	NA	4.5 (0.3-468)	6.4(0.9-471.5)
Median CA19-9 carbohydrate antigen U/mL (range)	NA	NA	368(2.0-60,800);p=0.60	NA	167 (1-6,373)	155 (1- 311276)
Median overall survival time (MST)	15.9 months (95% CI=8.9-23.0 months)	9.0 months (95 %CI 4.0–13.9)	8.9 months	12.5 months (95% CI, 9.0–15.4)	12.7 months (95% CI, 8.4–23.5 months),	11.6 months (95% CI, 7.3–15.6 months)
1-year survival rate	NA	ITT population: 44.7 % (95 %CI 29.0–61.5)	NA	52.9%	52.0% (95% CI, 31.2–69.2%);p=0.02	44.4%
Complete response (CR)	1 (2.6%)	1	0	NA	NA	2(6%)
Partial response (PR)	5 (13.2%)	6	6 (20%)	NA	7 (30.4%)	10(29%)
Stable Disease	20(52.6%)	19	15 (50%)	NA	13 (56.5%)	17(49%)
Progressive Disease	6 (15.8%)	8	8(26.7%)	NA	NA	NA
overall response rate ( ORR)	15.8%	Per-protocol [PP] population:7(20.6 % , 95 % CI 8.5–36.7) Intention-to-treat [ITT] population:7(18.4 % ,95 %CI 6.1–30.7)	6(20%)	NA	30.4%	34.3%
Disease control rate	68.4%	PP population: 26 (76.5 %, 95 %CI 60.6–87.6) ITT population: 26(68.4%, 95% Cl 52.5-80.9)	21(70%)	NA	87%	82.9%
Median progression free survival (PFS)	5.8 months	4.4 months (95 %CI 1.8–6.9)	NA	7.1 months (95% CI, 5.7–8.6)	NA	6 month=48.8
Median time-to- progression	5.8 months (95% CI, 3.1-8.5 months)	NA	5.6 months	NA	NA	5.9 months (95% CI, 4.0–7.7 months)

Table: Table 1

Disclosures:
Faiza Ahmed indicated no relevant financial relationships.
Ujala Nasr indicated no relevant financial relationships.
Ammu Susheela indicated no relevant financial relationships.
Faiza Zakaria indicated no relevant financial relationships.
Sundus Ali indicated no relevant financial relationships.
Alaa Hamdan indicated no relevant financial relationships.
Anusha Sajja indicated no relevant financial relationships.
Kim Andrews indicated no relevant financial relationships.
Sai Harsha Bobba indicated no relevant financial relationships.
Shanthi Potla indicated no relevant financial relationships.
Aysha Aslam indicated no relevant financial relationships.
Marc-Darlene Mezidor indicated no relevant financial relationships.
Zeynep Yukselen indicated no relevant financial relationships.
Karthik Mohan indicated no relevant financial relationships.
Raza Zarrar indicated no relevant financial relationships.
Endrit Shahini indicated no relevant financial relationships.
Thiruvengadam Muniraj indicated no relevant financial relationships.

Faiza Ahmed, MD, MS, BSc¹, Ujala Nasr, MD², Ammu Susheela, MD³, Faiza Zakaria, MD², Sundus Ali, MD⁴, Alaa Hamdan, MD¹, Anusha Sajja, MD¹, Kim Andrews, MD, PhD, MHA⁵, Sai Harsha Bobba, MD⁶, Shanthi Potla, MD⁷, Aysha Aslam, MD⁸, Marc-Darlene Mezidor, MD⁹, Zeynep Yukselen, MD¹, Karthik Mohan, DO¹, Raza Zarrar, MD¹⁰, Endrit Shahini, MSc, MD¹¹, Thiruvengadam Muniraj, MD, PhD, MRCP¹². P2124 - Effectiveness of Gemcitabine Plus S-1 Combination as First-Line Therapy Tested in Japanese Population for Advanced Biliary Tract Cancer: Systematic Review of Clinical Trials, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.