Addition of anti-PD1 antibodies to chemotherapy (CT) in first-line treatment of advanced esophageal cancer (EC): A systematic review and meta-analysis.

Authors

null

Anastasia Rice

Federal State Budgetary Institution, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Moscow, Russian Federation

Anastasia Rice , Mikhail Fedyanin , Ekaterina Ignatova , Elizaveta Polyanskaya , Elmira Dinaeva , Natalia Besova , Alexey Tryakin

Organizations

Federal State Budgetary Institution, N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation, Moscow, Russian Federation, Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation, Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology”оf the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation, Federal State Budgetary Institution N.N. Blokhin National Medical Research Center of Oncology оf the Ministry of Health of the Russian Federation (N.N. Blokhin NMRCO), Moscow, Russian Federation

Research Funding

No funding received

Background: The addition of anti-PD-1 antibodies to first-line CT is the new standard of care for pts with advanced EC. However, available data on the efficacy of such therapy in different clinical subgroups is still lacking. Therefore, we performed a meta-analysis to determine the efficacy of combination anti-PD1 and systemic CT in terms of overall survival (OS) in pts with advanced EC. Methods: We searched PubMed, proceedings of ASCO, and ESMO conferences up to February 2022. We included prospective randomized phase III trials comparing the combination of anti-PD1 and CT with CT alone as the first-line treatment option for pts with advanced EC. The primary outcome was OS. Meta-analysis was conducted by Review Manager (Ver. 5.3) software. Results: Five trials with a total of 3163 pts were included, of which 1576 received anti-PD1+CT and 1587 received CT alone. There was a significant improvement in PFS (HR, 0.62; 95% CI, 0.56-0.67; p < 0.00001; I2 = 45%, p for heterogeneity 0.12), OS (HR, 0.69; 95% CI, 0.63-0.76; p < 0.00001; I2 = 0%) and ORR (OR, 2.07; 95% CI, 1.76-2.43; p < 0.00001; I2 = 21%) in pts received anti-PD1+CT. OS was improved in pts regardless of age, race, CT regimen, presence of liver metastases, ECOG PS, or histology. Subgroup analysis suggested that the addition of anti-PD1 have a better effect in pts with PDL expression on tumor cells > 1, ≥ 10, and < 10 and in pts with CPS ≥ 10, but not in pts with PDL < 1. We found a tendency towards survival advantage in pts with CPS < 10. No survival benefit was observed in women (tab). Conclusions: Improved OS was found to be associated with addition of anti-PD1 antibodies to systemic CT in different patient subgroups with advanced EC, except for female and in pts with low PDL expression. Despite of meta-analysis results we need prospective randomized trial for pts with CPS < 10.

Factors
HR (95% CI)
p
I2 (p for heterogeneity)
Man
0.65 (0.58-0.73)
< 0.00001
0% (0.91)
Women
0.85 (0.67-1.07)
0.16
0% (0.42)
Asian race
0.65 (0.59-0.72)
< 0.00001
0% (0.51)
Non-Asian races
0.68 (0.59-0.78)
< 0.00001
0% (0.64)
Age < 65
0.73 (0.63-0.84)
< 0.00001
0% (0.72)
Age ≥ 65
0.6 (0.5-0.73)
< 0.00001
0% (0.75)
ECOG PS 0
0.57 (0.47-0.7)
< 0.00001
0% (0.98)
ECOG PS 1
0.7 (0.61-0.8)
< 0.00001
0% (0.61)
Liver metastases
0.6 (0.44-0.81)
0.0008
0% (0.96)
Without liver metastases
0.7 (0.6-0.83)
< 0.00001
0% (0.34)
Squamous histology
0.7 (0.62-0.78)
< 0.00001
0% (0.7)
Adenocarcinoma
0.7 (0.54-0.92)
0.01
0% (0.52)
PDL expression < 1
0.9 (0,73-1.11)
0.32
0% (0.33)
PDL expression ≥ 1
0.72 (0.56-0.91)
0.007
0% (0.83)
PDL expression < 10
0.79 (0.66-0.94)
0.007
0% (0.94)
PDL expression ≥ 10
0.57 (0.43-0.75)
< 0.0001
0% (0.54)
PDL expression CPS < 10
0.75 (0.56-1.0)
0.05
68% (0.08)
PDL expression CPS ≥ 10
0.64 (0.54-0.76)
< 0.00001
0% (0.59)
Cisplatin plus fluorouracil
0.67 (0.58-0.77)
< 0.00001
0% (0.37)
Cisplatin plus paclitaxel
0.67 (0.57-0.78)
< 0.00001
0% (0.61)

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Abstract Details

Meeting

2022 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Track

Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Sub Track

Esophageal or Gastric Cancer

Citation

J Clin Oncol 40, 2022 (suppl 16; abstr e16055)

DOI

10.1200/JCO.2022.40.16_suppl.e16055

Abstract #

e16055

Abstract Disclosures