Interim results analysis of the PERFECTION observational study in patients with metastatic non-small cell lung cancer

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Abstract

Aim. To evaluate the efficacy and safety profile of the pembrolizumab biosimilar, Pembroria, in patients with advanced lung cancer in routine clinical practice.

Materials and methods. The patients eligible for pembrolizumab therapy based on standard clinical indications and without contraindications participated in the multicenter, multicohort, post-marketing, prospective, non-interventional study. The primary endpoint was the best objective response rate (ORR) assessed within six months of treatment initiation. This report presents interim analysis for patients with non-squamous non-small cell lung cancer (nsNSCLC) and squamous non-small cell lung cancer (sNSCLC) using Fleming’s two-stage single-arm design (stages g1 and g2). Thresholds for hypothesis testing and sample size determination were based on established literature benchmarks.

Results

Non-squamous NSCLC. Stage g1 enrolled 20 patients with a median age of 64 years. The follow-up period for assessing the best objective response was 2.57 months. An objective response was achieved in 55% (11/20) of patients, meeting predefined efficacy criteria at stage g1.

Squamous NSCLC. Stage g1 included 23 patients and based on the results of stage g1, the study proceeded to stage g2 with the enrollment of an additional 23 patients in stage g2, yielding a total of 46 participants with a median age of 66 years. An ORR of 47.8% (22/46) was observed, confirming efficacy of the pembrolisumab biosimilar at stage g2. The median follow-up period to the objective response assessment was 2.88 months.

Across the six-month follow-up period, nine adverse events (AEs) were reported among seven patients (8.4%) in the NSCLC cohort. Four AEs were considered therapy-related and classified as Grade 2 per CTCAE v5.0. No AEs Grade 4/5 were recorded.

Conclusion. In the NSCLC cohort, the pembrolizumab biosimilar (Pembroria) has demonstrated an ORR comparable to that of the reference pembrolizumab reported in clinical trials for both nsNSCLC and sNSCLC, regardless of PD-L1 expression levels or pembrolizumab treatment regimens. These findings support the real-world efficacy and safety of Pembroria in a diverse patient population.

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Introduction

Over the past decade, significant advancements have been made in the treatment of advanced non-small cell lung cancer (NSCLC), mainly due to the introduction of immune checkpoint inhibitors (ICIs) into clinical practice. These therapies, utilized both as monotherapy and in combination with other antitumor agents, have revolutionized the therapeutic landscape. ICIs function by reactivating the specific adaptive antitumor immune response of T cells, reversing immune escape mechanisms, and facilitating tumor cell death. Pembrolizumab (Keytruda®) was the first ICI approved in Russia for the treatment of advanced NSCLC. It is indicated for patients with confirmed PD-L1 expression on tumor cells (≥1%) and disease progression during or after platinum-based chemotherapy. The efficacy of pembrolizumab for this indication has been established through four pivotal phase III randomized trials [1–4]. Furthermore, a network meta-analysis of 17 randomized trials encompassing 7,792 NSCLC patients identified pembrolizumab combined with chemotherapy as the top-ranked therapy for achieving disease control compared to other ICIs and their combinations [5]. As a result, pembrolizumab remains a first-line therapeutic option and is consistently included in international and Russian clinical guidelines for NSCLC treatment [6, 7].

In 2022, Pembroria, the first biosimilar of pembrolizumab developed by JSC “BIOCAD,” was approved in Russia. Comprehensive analytical assessments, including comparative physical, chemical, and functional characterizations, confirmed its biosimilarity to the reference pembrolizumab (Keytruda®). Clinical studies further established the equivalence of pembrolizumab biosimilar in terms of pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity [8].

Real-world data (RWD) has emerged as a critical complement to clinical trials, offering insights into the effectiveness and safety of therapies in broader and heterogeneous patient populations [9]. To generate RWD for Pembroria (INN: pembrolizumab), BIOCAD initiated the PERFECTION study—a multicenter, multicohort, post-marketing, prospective, non-interventional trial aimed at evaluating its efficacy and safety in routine clinical practice.

This article reports interim findings from the PERFECTION study, focusing on using the pembrolizumab biosimilar in patients with metastatic non-squamous NSCLC (nsNSCLC) and metastatic squamous NSCLC (sNSCLC). These data provide valuable insights into the clinical utility of the biosimilar in real-world settings, contributing to the growing evidence supporting its integration into clinical practice.

Materials and methods

A multicenter, multicohort, post-marketing, prospective, non-interventional study was conducted to evaluate the efficacy and safety of Pembroria (INN: pembrolizumab) concentrate for solution for infusion (25 mg/mL, BIOCAD JSC, Russia), in patients with advanced malignancies of various localizations in real-world clinical practice. The study is being conducted in 70 centers across the Russian Federation. The primary endpoint is the objective response rate (ORR), defined as the proportion of patients achieving complete response (CR) or partial response (PR) as assessed by RECIST version 1.1 criteria within six months of treatment initiation. Secondary endpoints include the best objective response rate, progression-free survival, overall survival, and duration of response. Safety is evaluated continuously throughout the study and its assessment includes the incidence and nature of adverse events (AEs) and serious adverse events (SAEs), frequency of treatment discontinuations due to AEs/SAEs, proportion of patients with Grade 3–4 AEs (per CTCAE v5.0), incidence of immune-related AEs (e.g., pneumonitis, colitis, nephritis, endocrinopathies, hepatitis, and dermatologic reactions), and performance status as measured by the ECOG scale. Eligibility criteria: patients eligible for pembrolizumab treatment in routine clinical practice were included if they met standard clinical indications without contraindications and at the time of enrollment they had already initiated on-label Pembroria therapy (with at least one but no more than two doses administered).

Within the scope of the current non-interventional study, the therapy efficacy was preliminary assessed using the Fleming sequential design for a single-group study with two stages (g1 and g2) to test dichotomous endpoints (p) [10].

The results of the analysis will be presented separately for each of the following eight defined subgroups of patients: patients with metastatic non-small cell lung cancer (NSCLC); patients with squamous non-small cell lung cancer (sNSCLC); patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC); patients with locally advanced or metastatic urothelial cancer (UC); patients with advanced renal cell carcinoma (RCC); patients with metastatic or recurrent cervical cancer (CC); patients with advanced endometrial cancer without high microsatellite instability or mismatch repair deficiency (EC non-MSI-H/dMMR); patients with advanced endometrial cancer with high microsatellite instability or mismatch repair deficiency (EC MSI-H/dMMR). Interim efficacy assessments for each subgroup will be conducted using the Fleming method as patient enrollment reaches the pre-calculated sample sizes. Only the primary efficacy endpoint will be assessed during these analyses. Fleming’s design involves defining thresholds for acceptance (Ag) or rejection (Rg) of the null hypothesis, testing the proportion of responders (p) under the following conditions:

H0: p≤P0 (therapy is insufficiently effective) versus HA: p>P1 (therapy is acceptably effective and warrants further investigation)

 

Table 1. Established P0 and P1 threshold values, %

Subgroup

Study

ORR based on published data

ORR Control Group for Defining P0/P1

Thresholds

Р0

Р1

nsNSCLC

KEYNOTE-189

47.6 (95% CI: 42.6–52.5)

18.9

18

42

sNSCLC

KEYNOTE-407

62.6 (95% CI: 56.6–68.3)

38.4

35

57

 

An interim safety analysis across all subgroups is scheduled six months after the enrollment of the first patient.

This article focuses on the preliminary efficacy of Pembroria using the Fleming method for nsNSCLC and sNSCLC subgroups, as well as safety data for these patients. The P0 and P1 thresholds were defined based on pembrolizumab efficacy data from the KEYNOTE-189 [4, 11] and KEYNOTE-407 [3] studies for nsNSCLC and sNSCLC, respectively (Table 1).

Sample sizes for the Fleming method were calculated based on these thresholds. For nsNSCLC, stage g1 required 20 patients, with efficacy demonstrated if at least 9 patients responded and insufficient efficacy concluded if 3 or fewer patients responded. If 4 to 8 responses were observed, the study would proceed to stage g2 with an additional 20 patients. Efficacy at stage g2 would be confirmed if at least 12 of 40 patients responded. The statistical power was set at 0.95, with a Type I error rate of 0.044 (Figure 1).

For the squamous NSCLC (sNSCLC) cohort, the first stage (g1) requires the enrollment of 23 patients. If 8 or fewer patients achieve an objective response, the cohort will be closed due to insufficient efficacy. If 14 or more patients achieve a response, efficacy will be confirmed. If the response is observed in more than 8 but fewer than 14 patients, the study will proceed to the second stage (g2) with an additional 23 patients enrolled. At stage g2, the efficacy threshold will be confirmed if at least 22 of 46 patients achieve an objective response. The study's statistical power is 0.91, with an alpha error of 0.05 (Figure 2).

The objective response rate is defined as the proportion of patients with either a complete or partial objective response to treatment, according to RECIST 1.1 criteria for the assessment of solid tumor response. If a patient experiences at least one PR or CR during the study treatment period, that patient will be considered a responder. The analysis includes all assessments made during the first 6 months of therapy. If patients had their first response assessments within 6–9 months from the start of therapy, they could also be recorded for statistical analysis. Once the planned objective response rate is reached, enrollment in the study continues to evaluate the safety profile of the treatment.

Sample size calculations for a preliminary efficacy assessment in various subgroups were performed using Fleming's method. The target probability of Type I error was 5% (0.05) and the target power was 90–95% (0.90–0.95). Calculations were performed using PASS 2021 software (NCSS LLC, www.ncss.com).

Results

Non-Squamous Non-Small Cell Lung Cancer (nsNSCLC)

Stage g1 of the study included 20 patients who received at least one dose of Pembroria. Patient characteristics are summarized in Table 2. The median age of the overall population was 64 years, and most patients (70%) were male. An ECOG performance status of 1 was noted in 75% of all included patients. PD-L1 expression levels were determined in almost half of the patients. Data are presented for both the patients analyzed for ORR at stage g1 and all patients with nsNSCLC enrolled at the time of publication.

 

Table 2. Characteristics of included patients (nsNSCLC subgroup)

Characteristics

g1 (N=20)

Overall (N=40)

Median age (range), years

64 (40–74)

64 (20–76)

Male, n (%)

17 (85.0)

28 (70.0)

Female, n (%)

3 (15.0)

12 (30.0)

ECOG PS 0, n (%)

7 (35.0)

10 (25.0)

ECOG PS 1, n (%)

13 (65.0)

30 (75.0)

Current smoker, n (%)

12 (60.0)

22 (55.0)

Brain metastases, n (%)

0 (0.0)

3 (7.5)

Liver metastases, n (%)

2 (10.0)

3 (7.5)

Lung metastases, n (%)

9 (45.0)

18 (45.0)

PD-L1 expression determined, n (%)

9 (45.0)

21 (52.5)

PD-L1 expression, n (%)

TPS*<1%

1 (11.1)

6 (28.6)

TPS 1–49%

3 (33.3)

9 (42.8)

TPS≥50%

5 (55.5)

6 (28.6)

Prior therapy excluding ICIs, n (%)

Yes

2 (10.0)

5 (12.5)

Surgery performed for the primary disease

6 (30.0)

9 (22.5)

*Tumor Proportion Score (TPS).

 

 

Fig. 1. Study design for nsNSCLC patient subgroup

Рис. 1. Дизайн исследования для пациентов с нпНМРЛ.

 

Fig. 2. Study design for sNSCLC patient subgroup.

Рис. 2. Дизайн исследования для пациентов с пНМРЛ.

 

Most patients received pembrolizumab biosimilar in combination with pemetrexed and carboplatin – 16 (40.0%), while 17.5% received monotherapy. Most patients received pembrolizumab biosimilar at a dose of 200 mg every three weeks (Table 3).

The median follow-up period for ORR evaluation in stage g1 was 2.57 months, the maximum follow-up duration in this group was 4.9 months, and the mean value was 3.24. Objective tumor response was observed in 11 of 20 patients, corresponding to an ORR of 55% (Table 4). According to the study design, the efficacy threshold for stage g1 required at least 9 responses, confirming the efficacy of Pembroria for nsNSCLC.

Squamous Non-Small Cell Lung Cancer (sNSCLC)

Forty-six patients were enrolled across stages g1 (n=23) and g2 (n=23), with their characteristics presented in Table 5. The median age in stage g2 was 66 years, and 87% of patients were male. PD-L1 expression was determined in 69.6% of patients, with TPS≥50% observed in 34.8%.

Most patients received pembrolizumab biosimilar in combination with paclitaxel and carboplatin – 28 (60.9%), while 17 (37.0%) patients received monotherapy. Most patients received pembrolizumab at a dose of 200 mg every 3 weeks (Table 6).

The median follow-up duration for the assessment of the best objective response at stage g1 was 2.8 months, while at stage g2 (in all patients with this diagnosis), it was 2.88 months.

At stage g1, an objective tumor response to therapy was observed in 11 out of 23 patients with squamous NSCLC (sNSCLC). According to the study design, since the number of responses exceeded 8 but was fewer than 14 at stage g1, patient enrollment continued to evaluate the primary endpoint, and an additional 23 patients were included. At stage g2, an objective response was observed in 22 out of 46 patients (47.8%) (Table 7). At least 22 patients were required to achieve an objective response to confirm the efficacy of Pembroria at this stage. Thus, Pembroria demonstrated equivalence to the original pembrolizumab therapy regimen for the treatment of sNSCLC.

 

Table 3. Pembroria Therapy Regimens (nsNSCLC subgroup), n (%)

  

g1

Overall

Treatment scheme with Pembroria

Pembrolizumab, monotherapy

4 (20.0)

7 (17.5)

Pembrolizumab + paclitaxel + carboplatin

4 (20.0)

10 (25.0)

Pembrolizumab + pemetrexed + carboplatin

8 (40.0)

16 (40.0)

Pembrolizumab + pemetrexed + cisplatin

4 (20.0)

6 (15.0)

Other

0 (0.0)

1 (2.5)

Pembrolizumab dosage

200 mg q3wk

17 (85.0)

37 (92.5)

400 mg q6wk

3 (15.0)

3 (7.5)

 

Table 4. Treatment Response (nsNSCLC subgroup), n (%)

 

g1

Overall

Response assessment

Yes

16 (80.0)

33 (82.5)

No

4 (20.0)

7 (17.5)

Total

20 (100.0)

40 (100.0)

Objective response

No

9 (45.0)

20 (50.0)

Yes

11 (55.0)

20 (50.0)

Total

20 (100.0)

40 (100.0)

 

Table 5. Patient Characteristics (sNSCLC subgroup)

Characteristics

g1 (N=23)

Overall (N=46)

Median age (range). years

65 (37–78)

66 (37–78)

Male. n (%)

18 (78.3)

40 (87.0)

Female. n (%)

5 (21.7)

6 (13.0)

ECOG PS 0. n (%)

8 (34.8)

16 (34.8)

ECOG PS 1. n (%)

15 (65.2)

30 (65.2)

Current smoker. n (%)

12 (52.2)

25 (54.3)

Histological subtype. n (%)

sNSCLC. n (%)

23 (100.0)

46 (100.0)

Brain metastases. n (%)

5 (21.7)

6 (13.0)

Lung metastases. n (%)

11 (47.8)

23 (50.0)

Liver metastases. n (%)

1 (4.3)

4 (8.7)

PD-L1 expression determined. n (%)

19 (86.2)

32 (69.6)

PD-L1 expression. n (%)

TPS<1%

5 (21.7)

7 (15.2)

TPS 1–49%

4 (17.3)

9 (19.5)

TPS≥50%

10 (43.5)

16 (34.8)

Prior therapy. n (%)

Yes

1 (4.3)

5 (10.9)

Surgery performed for the primary disease

4 (17.4)

9 (19.6)

 

Table 6. Pembroria Therapy Regimens (sNSCLC subgroup). n (%)

 

g1

Overall

Treatment scheme with Pembroria

Pembrolizumab. monotherapy

10 (43.5)

17 (37.0)

Pembrolizumab + paclitaxel + carboplatin

12 (52.2)

28 (60.9)

Pembrolizumab + pemetrexed + carboplatin

1 (4.3)

1 (2.2)

Pembrolizumab dosage

200 mg q3wk

19 (82.6)

38 (82.6)

400 mg q6wk

4 (17.4)

8 (17.4)

 

Table 7. Treatment Response: sNSCLC. n (%)

 

g1

Overall

Response assessment

Yes

20 (87.0)

40 (87.0)

No

3 (13.0)

6 (13.0)

Total

23 (100.0)

46 (100.0)

Objective response

No

12 (52.2)

24 (52.2)

Yes

11 (47.8)

22 (47.8)

Total

23 (100.0)

46 (100)

 

Safety

Safety was analyzed for the combined NSCLC cohort (n=83). Over six months, 9 AEs were reported in 7 patients (8.4%) with nsNSCLC. Four AEs were considered likely therapy-related and were classified as Grade 2 per CTCAE v5.0. No serious adverse events and immune-mediated adverse events were reported in either group.

Discussion

Combination therapy with platinum-based doublet chemotherapy and immune checkpoint inhibitors (ICIs) is currently the standard of care for advanced non-small cell lung cancer (NSCLC) without driver mutations, based on findings from the KEYNOTE-189 and KEYNOTE-407 trials. The interim analysis of the PERFECTION prospective observational study included 40 patients with metastatic non-squamous NSCLC (nsNSCLC) and 46 patients with metastatic squamous NSCLC (sNSCLC) without EGFR or ALK genomic aberrations and a good functional status (ECOG PS 0 or 1). All patients received first-line pembrolizumab therapy, either as monotherapy or combined with platinum-based doublets, following approved treatment standards and the regulatory-approved prescribing information approved in December 2022.

In this preliminary assessment, the efficacy of Pembroria was demonstrated in patients with nsNSCLC during the first stage (g1) of analysis using Fleming’s method, with an objective response rate (ORR) of 55% (11 of 20 patients). For patients with sNSCLC, efficacy was confirmed during the second stage (g2) of analysis, with an ORR of 47.8% (22 of 46 patients). These findings are consistent with those reported in the KEYNOTE-189 and KEYNOTE-407 trials. Notably, in the sNSCLC cohort, 37.5% of patients received pembrolizumab biosimilar monotherapy, yet the observed ORR was comparable to data for the reference drug when used in combination with chemotherapy. The safety profile of Pembroria in this study differed slightly from those reported in KEYNOTE-189 and KEYNOTE-407. In those studies, Grade 3–5 treatment-related adverse events (AEs) were observed in 56.5% (KEYNOTE-407) and 52.3% (KEYNOTE-189) of patients [3, 12] treated with reference pembrolizumab. In contrast, no serious or immune-mediated AEs were reported in the PERFECTION study. Although the risk of AEs depends on the duration of therapy, the median follow-up period in this interim analysis was sufficient to evaluate the safety profile of Pembroria.

The safety findings from this interim analysis are consistent with data from a multicenter, double-blind, randomized phase I trial [13], which evaluated the pharmacokinetics, safety, and immunogenicity of Pembroria compared with reference pembrolizumab (Keytruda®) in patients with advanced metastatic or recurrent unresectable nsNSCLC and melanoma.

Limitations of this study include the relatively small sample size and short median follow-up period, which require more in-depth analysis. Also, Fleming’s method is primarily designed for early-stage evaluation of promising oncology drugs and is not intended for comprehensive comparisons between biosimilars and original reference drugs. Such comparisons are typically conducted during clinical trials for regulatory approval of biosimilars. However, it does provide an initial indication of comparable efficacy in nosologic units not studied in phase III trials, which is what was done in this preliminary analysis. The study is ongoing, and as more data become available, additional analyses will be performed to demonstrate the comparability of the Pembroria biosimilar and Kitruda® in different indications.

Conclusion

This interim analysis of the PERFECTION study offers clinically significant insights, as the patient population reflects real-world clinical practice. The observed efficacy of Pembroria, as measured by ORR, was comparable to that of reference pembrolizumab in both nsNSCLC and sNSCLC cohorts, irrespective of PD-L1 expression levels or treatment regimens. Importantly, safety monitoring showed no new safety concerns, supporting the pembrolizumab biosimilar concordance with the established safety profile of reference pembrolizumab.

Disclosure of interest. The authors declare that they have no competing interests.

Authors’ contribution. All authors made a substantial contribution to the conception of the work, acquisition, analysis, interpretation of data for the work, drafting and revising the work, final approval of the version to be published and agree to be accountable for all aspects of the work.

Funding source. This study was supported by BIOCAD JSC. During the preparation of the manuscript, the authors maintained their independence of opinion.

Consent for publication. Written consent was obtained from the patients for publication of relevant medical information and all of accompanying images within the manuscript.

Ethics approval. The study was conducted following the Declaration of Helsinki and the National Standard of Good Clinical Practice. The study was approved by an of the independent Interdisciplinary Committee for Ethical Review of Clinical Research 03.02.2023.

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About the authors

Konstantin K. Laktionov

Blokhin National Medical Research Center of Oncology; Pirogov Russian National Research Medical University (Pirogov University)

Author for correspondence.
Email: lkoskos@mail.ru
ORCID iD: 0000-0003-4469-502X

D. Sci. (Med.), Prof.

Russian Federation, Moscow; Moscow

Mikhail Fedyanin

Blokhin National Medical Research Center of Oncology; Pirogov National Medical and Surgical Center; Moscow Multidisciplinary Clinical Center „Kommunarka“

Email: lkoskos@mail.ru
ORCID iD: 0000-0001-5615-7806
SPIN-code: 4381-5628

D. Sci. (Med.)

Russian Federation, Moscow; Moscow; Moscow

Daniil L. Stroyakovskiy

Moscow City Oncology Hospital No. 62

Email: lkoskos@mail.ru
ORCID iD: 0000-0003-1973-1092

Cand. Sci. (Med.)

Russian Federation, Moscow

Anastasiia S. Mochalova

Medsi group JSC

Email: lkoskos@mail.ru

D. Sci. (Med.)

Russian Federation, Moscow

Aishat R. Iasieva

Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department

Email: lkoskos@mail.ru

oncologist, Moscow State Budgetary Healthcare Institution "Oncological Center No. 1

Russian Federation, Moscow

Natal'ia V. Fadeeva

Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine

Email: lkoskos@mail.ru

Cand. Sci. (Med.)

Russian Federation, Chelyabinsk

Iuliia S. Shapovalova

Clinical Hospital “RZD-Medicine” of Chelyabinsk

Email: lkoskos@mail.ru

Cand. Sci. (Med.)

Russian Federation, Chelyabinsk

Oleg V. Mironov

Tambov Regional Oncologic Clinical Dispensary

Email: lkoskos@mail.ru

oncologist

Russian Federation, Tambov

Aleksandr S. Dergunov

Tver Regional Clinical Oncologic Dispensary

Email: lkoskos@mail.ru

Department Head

Russian Federation, Tver

Sergey V. Orlov

Pavlov First Saint Petersburg State Medical University

Email: lkoskos@mail.ru
SPIN-code: 7517-4104

D. Sci. (Med.), Prof.

Russian Federation, Saint Petersburg

Leonid A. Vasilev

Current Medical Technologies JSC; Institute of Modern Medical Technologies

Email: lkoskos@mail.ru
ORCID iD: 0000-0003-1200-1468

D. Sci. (Med.)

Russian Federation, St. Petersburg; St. Petersburg

El'vira A. Bobrova

Loginov Moscow Clinical Scientific Center

Email: lkoskos@mail.ru

oncologist

Russian Federation, Moscow

Svetlana A. Orlova

Republican Clinical Oncologic Dispensary

Email: lkoskos@mail.ru

Department Head

Russian Federation, Cheboksary

Antonina A. Kosukhina

Belgorod Regional Oncologic Dispensary

Email: lkoskos@mail.ru

Department Head, Belgorod Regional Oncologic Dispensary

Russian Federation, Belgorod

Natal'ia I. Polshina

Loginov Moscow Clinical Scientific Center

Email: lkoskos@mail.ru

oncologist

Russian Federation, Moscow

Sergei G. Vardanian

Moscow Multidisciplinary Clinical Center „Kommunarka“

Email: lkoskos@mail.ru

oncologist

Russian Federation, Moscow

Aleksei Iu. Fedoseev

Moscow Multidisciplinary Clinical Center „Kommunarka“

Email: lkoskos@mail.ru

oncologist

Russian Federation, Moscow

Karina Sh. Tumasian

Belgorod Regional Oncologic Dispensary

Email: lkoskos@mail.ru

Deputy Chief doctor, Belgorod Regional Oncologic Dispensary

Russian Federation, Belgorod

Anastasiia E. Danilova

City Polyclinic No. 106

Email: lkoskos@mail.ru

oncologist

Russian Federation, St. Petersburg

Tatiana V. Krashikhina

Moscow Center for Rehabilitation Treatment LLC

Email: lkoskos@mail.ru
ORCID iD: 0000-0001-7567-8308

 Cand. Sci. (Med.)

Russian Federation, Moscow

Ekaterina I. Tsygankova

Sergiev Posad Hospital No. 2

Email: lkoskos@mail.ru

oncologist

Russian Federation, Sergiev Posad

Dmitrii E. Staritsyn

Severodvinsk City Clinical Hospital No. 2 of Emergency Medical Care

Email: lkoskos@mail.ru

oncologist

Russian Federation, Severodvinsk

Ol'ga V. Toporkova

Tambov Regional Oncologic Clinical Dispensary

Email: lkoskos@mail.ru

oncologist

Russian Federation, Tambov

Mira V. Boskhomdzhieva

Timoshkaeva Republican Oncologic Dispensary

Email: lkoskos@mail.ru

Deputy Chief doctor

Russian Federation, Elista

Alexander V. Sultanbaev

Republican Clinical Oncology Dispensary; Bashkir State Medical University

Email: lkoskos@mail.ru

Cand. Sci. (Med.)

Russian Federation, Ufa; Ufa

Margarita V. Edamenko

Belgorod Regional Oncologic Dispensary

Email: lkoskos@mail.ru

oncologist

Russian Federation, Belgorod

Vadim N. Dmitriev

Belgorod Regional Oncologic Dispensary

Email: lkoskos@mail.ru

D. Sci. (Med.)

Russian Federation, Belgorod

Aleksandr V. Shkradiuk

Efetov Crimean Republican Oncologic Clinical Dispensary

Email: lkoskos@mail.ru

Department Head

Russian Federation, Simferopol

Konstantin A. Shkret

Central City Clinical Hospital No. 24

Email: lkoskos@mail.ru

Department Head

Russian Federation, Ekaterinburg

Oxana N. Prosianikova

BIOCAD JSC

Email: lkoskos@mail.ru
ORCID iD: 0009-0005-3684-6301

Cand. Sci. (Med.)

Russian Federation, St. Petersburg

Evgeny V. Svechnikov

BIOCAD JSC

Email: lkoskos@mail.ru
ORCID iD: 0009-0003-0556-1931

Cand. Sci. (Med.)

Russian Federation, St. Petersburg

Semyon Yu. Grigorchuk

BIOCAD JSC

Email: lkoskos@mail.ru

Oncology group manager

Russian Federation, St. Petersburg

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Supplementary files

Supplementary Files
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2. Fig. 1. Study design for nsNSCLC patient subgroup.

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3. Fig. 2. Study design for sNSCLC patient subgroup.

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4. Fig. 1. Study design for nsNSCLC patient subgroup.

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5. Fig. 2. Study design for sNSCLC patient subgroup.

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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от 18.12.2015 г.