PMID- 38347177
OWN - NLM
STAT- MEDLINE
DCOM- 20240318
LR  - 20240319
IS  - 1573-0646 (Electronic)
IS  - 0167-6997 (Print)
IS  - 0167-6997 (Linking)
VI  - 42
IP  - 2
DP  - 2024 Apr
TI  - PD-1 inhibitor combined with albumin paclitaxel and apatinib as second-line 
      treatment for patients with metastatic gastric cancer: a single-center, 
      single-arm, phase II study.
PG  - 171-178
LID - 10.1007/s10637-024-01425-3 [doi]
AB  - BACKGROUND: Immune checkpoint inhibitors have been approved for first- and 
      third-line treatment of advanced gastric cancer. However, pembrolizumab alone in 
      the second line did not improve overall survival compared to chemotherapy in the 
      KEYNOTE-061 study. In this study, we aimed to explore the efficacy and safety of 
      a three-drug regimen of PD-1 inhibitor combined with albumin paclitaxel and 
      apatinib (a VEGFR inhibitor) for the second-line treatment of patients with 
      metastatic gastric cancer (mGC). METHODS: This was a single-center, single-arm, 
      phase II clinical study. Patients with mGC with stable microsatellite and 
      negative HER-2 expression who failed first-line chemotherapy were enrolled. The 
      enrolled patients were treated with PD-1 inhibitor (selected according to 
      patients' requirements) in combination with albumin paclitaxel (125 mg/m(2), 
      intravenously, days 1 and 8, or 250 mg/m(2), intravenously, day 1) and apatinib 
      (250 or 500 mg, orally, days 1-21) every 3 weeks. The primary endpoint was 
      progression-free survival (PFS), and the secondary endpoints were overall 
      survival (OS), objective response rate (ORR), disease control rate (DCR), 
      duration of response, and adverse events (AEs). RESULTS: From July 11, 2019, to 
      October 13, 2022, a total of 43 patients were enrolled, of whom 10 were PD-L1 
      negative, 11 were PD-L1 positive, and 22 had unknown PD-L1 expression. As of the 
      data cutoff on April 1st, 2023, nine patients had partial response, 29 had stable 
      disease, and five experienced progressive disease, with the ORR of 20.9% and DCR 
      of 88.3%. The median PFS was 6.2 months (95% CI, 3.9-9.3), and the median OS was 
      10.1 months (95% CI, 7.5-14.1). All patients suffered from alopecia and 
      neurotoxicity. The other main AEs of grade 1 or 2 were bone marrow suppression 
      (N = 21, 48.8%), hand-foot reaction (N = 19, 44.2%), hypertension (N = 18, 
      41.9%), hypothyroidism (N = 11, 25.6%), gastrointestinal bleeding (N = 3, 7.0%), 
      and liver function damage (N = 5, 11.6%). Two patients reported grade 3-4 
      immune-related liver damage. CONCLUSION: Second-line PD-1 inhibitor combined with 
      albumin paclitaxel and apatinib showed certain efficacy and safety in patients 
      with mGC. TRIAL REGISTRATION: Clinical trials, NCT04182724. Registered 27 
      November 2019; retrospectively registered, 
      https://clinicaltrials.gov/study/NCT04182724.
CI  - (c) 2024. The Author(s).
FAU - Gou, Miaomiao
AU  - Gou M
AD  - Medical Oncology Department, The Fifth Medical Center, Chinese People's 
      Liberation Army General Hospital, Haidian District, Fuxing Road 28, Beijing, 
      100853, People's Republic of China.
FAU - Zhang, Yong
AU  - Zhang Y
AD  - Medical Oncology Department, The Second Medical Center, Chinese People's 
      Liberation Army General Hospital, Beijing, People's Republic of China.
FAU - Wang, Zhikuan
AU  - Wang Z
AD  - Medical Oncology Department, The Fifth Medical Center, Chinese People's 
      Liberation Army General Hospital, Haidian District, Fuxing Road 28, Beijing, 
      100853, People's Republic of China.
FAU - Qian, Niansong
AU  - Qian N
AD  - Respiratory and Critical Care Medicine Department, The Eighth Medical Center, 
      Chinese People's Liberation Army General Hospital, Beijing, People's Republic of 
      China. 18701317301@qq.com.
FAU - Dai, Guanghai
AU  - Dai G
AD  - Medical Oncology Department, The Fifth Medical Center, Chinese People's 
      Liberation Army General Hospital, Haidian District, Fuxing Road 28, Beijing, 
      100853, People's Republic of China. daigh60@sohu.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT04182724
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20240212
PL  - United States
TA  - Invest New Drugs
JT  - Investigational new drugs
JID - 8309330
RN  - P88XT4IS4D (Paclitaxel)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 5S371K6132 (apatinib)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Albumins)
RN  - 0 (Pyridines)
SB  - IM
MH  - Humans
MH  - *Paclitaxel/adverse effects
MH  - Immune Checkpoint Inhibitors/therapeutic use
MH  - *Stomach Neoplasms/drug therapy/etiology
MH  - B7-H1 Antigen
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Albumins/therapeutic use
MH  - *Pyridines
PMC - PMC10944415
OTO - NOTNLM
OT  - Albumin paclitaxel
OT  - Endpoint
OT  - Metastatic gastric cancer
OT  - Second line
COIS- The authors declare no competing interests.
EDAT- 2024/02/13 00:42
MHDA- 2024/03/18 06:44
PMCR- 2024/02/12
CRDT- 2024/02/12 23:28
PHST- 2023/12/14 00:00 [received]
PHST- 2024/01/22 00:00 [accepted]
PHST- 2024/03/18 06:44 [medline]
PHST- 2024/02/13 00:42 [pubmed]
PHST- 2024/02/12 23:28 [entrez]
PHST- 2024/02/12 00:00 [pmc-release]
AID - 10.1007/s10637-024-01425-3 [pii]
AID - 1425 [pii]
AID - 10.1007/s10637-024-01425-3 [doi]
PST - ppublish
SO  - Invest New Drugs. 2024 Apr;42(2):171-178. doi: 10.1007/s10637-024-01425-3. Epub 
      2024 Feb 12.