Clinical and morphological features in patients with advanced endometrial cancer treated with immunotargeting therapy

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Abstract

Background. Endometrial cancer (EC) is one of the most significant oncogynecological problems. The main mortality cause in this disease, as in the case of other malignant neoplasms, is the tumor progression. The presence of mutations associated with mismatch repair-deficient is of great prognostic importance. Immunotargeting therapy (ITT), lenvatinib in combination with pembrolizumab, seems to be the most effective solution in the second line treatment of advanced EC without microsatellite instability. At the same time, the group of such patients is heterogeneous in terms of progression-free survival (PFS) on ITT. So that it determines the continuing need to search for reliable parameters steadily associated with the PFS duration in this type of treatment.

Aim. To analyze the clinical and morphological features in patients with advanced EC depending on the PFS duration on ITT. Materials and methods. The study included data on patients (n = 36) with advanced EC who received ITT in oncological dispensaries in Siberia and the Russian Far East. The overall patients’ group was analyzed using the Kaplan-Meier method. PFS was defined as the time from the ITT initiation until progression or death against the background of treatment. The influence of the selected factors (clinical and morphological parameters, treatment features, and adverse events) on PFS was assessed using a log-rank criterion. The study participants were then divided into 2 subgroups (15 women and 9 women) according to median PFS. Mann–Whitney tests for independent samples (quantitative measures), and Fisher’s tests (qualitative measures) were used to identify significant differences in comparison subgroups for the selected factors. Differences were considered statistically significant when the significance level was reached (p <0.05); data at the statistical trend level (p <0.10) were also discussed.

Results. In the study group, median PFS on ITT was 9.7 months (cut-off point), which was accepted as a response criterion. Among the 74 parameters reflecting clinical and morphological features in patients with advanced EC, metastatic lesions of pelvic lymph nodes (p = 0.028), para-aortic lymph nodes (p = 0.014), bone metastases (p = 0.080), and degree of estrogen receptor expression in tumor cells (p = 0.071) were associated with PFS. Partial regression as the maximal response to ITT (62.5 % vs 7.14 %, p = 0.011), as well as longer duration of response (median PFS 15.11 ± 1.10 months vs 4.47 ± 0.57 months, p = 0.00007), and the absence of foci in the pelvic/para-aortic lymph nodes (89 % vs 50 %, p = 0.069, and 89 % vs 47 %, p = 0.048, respectively), were more frequently observed in patients with a duration of median PFS ≥9.7 months compared to those with progression before 9.7 months. Stabilization as the maximum response to ITT (78.6 % vs 37.5 %, p = 0.072) was more frequently registered in the subgroup of patients with progression up to 9.7 months.

Conclusion. ITT can be considered as a potentially promising therapeutic option in advanced EC. Further research in this direction should be aimed at finding criteria to identify patients with EC who would have most benefit from this type of therapy more accurately.

About the authors

L. A. Kolomiets

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University, Ministry of Health of Russia

Author for correspondence.
Email: kolomietsla@oncology.tomsk.ru
ORCID iD: 0000-0002-6854-8940

Larisa A. Kolomiets.

5 Kooperativnyy Pereulok, Tomsk 634009; 2 Moskovskiy Trakt, Tomsk 634050

Russian Federation

M. N. Stakheeva

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical University, Ministry of Health of Russia; National Research Tomsk State University, Ministry of Education and Science of Russia

ORCID iD: 0000-0003-0601-2240

5 Kooperativnyy Pereulok, Tomsk 634009; 2 Moskovskiy Trakt, Tomsk 634050; 36 Lenina Prospekt, Tomsk 634050

Russian Federation

O. N. Churuksaeva

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID iD: 0000-0003-3439-8830

5 Kooperativnyy Pereulok, Tomsk 634009

Russian Federation

A. B. Villert

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID iD: 0000-0002-2773-1917

5 Kooperativnyy Pereulok, Tomsk 634009

Russian Federation

A. L. Chernyshova

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences

ORCID iD: 0000-0002-8194-2811

5 Kooperativnyy Pereulok, Tomsk 634009

Russian Federation

V. G. Sisakyan

Siberian State Medical University, Ministry of Health of Russia; Novosibirsk Regional Clinical Oncology Center

2 Moskovskiy Trakt, Tomsk 634050; 2 Plakhotnogo St., Novosibirsk 630108

Russian Federation

I. Yu. Lots

Novosibirsk Regional Clinical Oncology Center

ORCID iD: 0009-0004-0139-4491

2 Plakhotnogo St., Novosibirsk 630108

Russian Federation

N. M. Chernorubashkina

Regional Oncology Center

32 Frunze St., Irkutsk 664035

Russian Federation

V. N. Zhurman

Primorsky Regional Oncology Center; Pacific State Medical University, Ministry of Health of Russia

59 Russkaya St., Vladivostok 690105; 2 Ostryakova Prospekt, Vladivostok 690002

Russian Federation

A. A. Grechkina

Primorsky Regional Oncology Center

59 Russkaya St., Vladivostok 690105

Russian Federation

E. N. Aleksandrova

Yakut Republican Oncology Center

Build. 1, 81 Stadukhina St., Yakutsk 677005

Russian Federation

N. E. Musaeva

A.I. Kryzhanovsky Krasnoyarsk Regional Oncological Center

16 1-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

O. V. Diduk

A.I. Kryzhanovsky Krasnoyarsk Regional Oncological Center

16 1-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

N. A. Bulygina

A.I. Kryzhanovsky Krasnoyarsk Regional Oncological Center

16 1-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

D. A. Pyatina

A.I. Kryzhanovsky Krasnoyarsk Regional Oncological Center

16 1-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

I. L. Obraz

A.I. Kryzhanovsky Krasnoyarsk Regional Oncological Center

16 1-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

A. V. Krechetova

A.I. Kryzhanovsky Krasnoyarsk Regional Oncological Center

16 1-ya Smolenskaya St., Krasnoyarsk 660133

Russian Federation

M. A. Danilova

Sakhalin Regional Oncology Center

3 Gorkogo St., Yuzhno-Sakhalinsk 693010

Russian Federation

M. A. Khodzhakhova

M.S. Rappoport Kuzbass Clinical Oncology Center

35 Volgogradskaya St., Kemerovo 650036

Russian Federation

A. A. Malsteva

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences

5 Kooperativnyy Pereulok, Tomsk 634009

Russian Federation

N. A. Ermak

Oncology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences

5 Kooperativnyy Pereulok, Tomsk 634009

Russian Federation

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