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Interim results analysis of the PERFECTION observational study in patients with metastatic non-small cell lung cancer
Laktionov KK, Fedyanin M, Stroyakovskiy DL, Mochalova AS, Iasieva AR, Fadeeva NV, Shapovalova IuS, Mironov OV, Dergunov AS, Orlov SV, Vasilev LA, Bobrova EA, Orlova SA, Kosukhina AA, Polshina NI, Vardanian SG, Fedoseev AIu, Tumasian KSh, Danilova AE, Krashikhina TV, Tsygankova EI, Staritsyn DE, Toporkova OV, Boskhomdzhieva MV, Sultanbaev AV, Edamenko MV, Dmitriev VN, Shkradiuk AV, Shkret KA, Prosianikova ON, Svechnikov EV, Grigorchuk SYu. Interim results analysis of the PERFECTION observational study in patients with metastatic non-small cell lung cancer. Journal of Modern Oncology. 2024;26(4):454–466. DOI: 10.26442/18151434.2024.4.203109
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Аннотация
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.
Keywords: immunotherapy, lung cancer, pembrolizumab, non-small cell lung cancer
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.
Keywords: immunotherapy, lung cancer, pembrolizumab, non-small cell lung cancer
Полный текст
Список литературы
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8. Fedyanin MYu, Snegovoy AV, Breder VV, et al. Toxicity Associated with Immune Checkpoint Inhibitors: Analysis of Immune-Related Adverse Events with a Pembrolizumab Biosimilar (Pembroria). Safety and Risk of Pharmacotherapy. 2023;11(2):215-30 (in Russian). DOI:10.30895/2312-7821-2023-11-2-360
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DOI:10.1186/s12874-020-01017-8
11. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078-02. DOI:10.1056/NEJMoa1801005
12. Rodríguez-Abreu D, Powell SF, Hochmair MJ, et al. Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Ann Oncol. 2021;32(7):881-95. DOI:10.1016/j.annonc.2021.04.008
13. Electronic resource. Unified register of registered medicinal products of the Eurasian Economic Union. Expert report on the assessment of the safety, efficacy and quality of Pembrolizumab as of 09.10.2024. Available at: https://portal.eaeunion.org/sites/commonprocesses/ru-ru/Pages/CardView.aspx?documentId=65f82ba030dcf.... Accessed: 26.11.2024 (in Russian).
2. Mok TSK, Wu YL, Kudaba I, et al. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019;393(10183):1819-80. DOI:10.1016/S0140-6736(18)32409-7
3. Paz-Ares L, Vicente D, Tafreshi A, et al. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020;15(10):1657-69. DOI:10.1016/j.jtho.2020.06.015
4. Garassino MC, Gadgeel S, Esteban E, et al. Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(3):387-97. DOI:10.1016/S1470-2045(19)30801-0
5. Zhang X, Wu M, Chen J, et al. Comparative efficacy of immune checkpoint inhibitors combined with chemotherapy in patients with advanced driver-gene negative non-small cell lung cancer: A systematic review and network meta-analysis. Heliyon. 2024;10(10):e30809. DOI:10.1016/j.heliyon.2024.e30809
6. Malignant neoplasms of the bronchi and lung. Clinical recommendations of the Ministry of Health of the Russian Federation, 2022. Available at: https://cr.minzdrav.gov.ru/preview-cr/30_4. Accessed: 26.11.2024 (in Russian).
7. Riely GJ, Wood DE, Ettinger DS, et al. Non-Small Cell Lung Cancer, Version 4.2024, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2024;22(4):249-74. DOI:10.6004/jnccn.2204.0023
8. Fedyanin MYu, Snegovoy AV, Breder VV, et al. Toxicity Associated with Immune Checkpoint Inhibitors: Analysis of Immune-Related Adverse Events with a Pembrolizumab Biosimilar (Pembroria). Safety and Risk of Pharmacotherapy. 2023;11(2):215-30 (in Russian). DOI:10.30895/2312-7821-2023-11-2-360
9. Castelo-Branco L, Pellat A, Martins-Branco D, et al. ESMO Guidance for Reporting Oncology real-World evidence (GROW). Ann Oncol. 2023;34(12):1097-112. DOI:10.1016/j.annonc.2023.10.001
10. Qin F, Wu J, Chen F, et al. Optimal, minimax and admissible two-stage design for phase II oncology clinical trials. BMC Med Res Methodol. 2020;20(1):126.
DOI:10.1186/s12874-020-01017-8
11. Gandhi L, Rodríguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(22):2078-02. DOI:10.1056/NEJMoa1801005
12. Rodríguez-Abreu D, Powell SF, Hochmair MJ, et al. Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189. Ann Oncol. 2021;32(7):881-95. DOI:10.1016/j.annonc.2021.04.008
13. Electronic resource. Unified register of registered medicinal products of the Eurasian Economic Union. Expert report on the assessment of the safety, efficacy and quality of Pembrolizumab as of 09.10.2024. Available at: https://portal.eaeunion.org/sites/commonprocesses/ru-ru/Pages/CardView.aspx?documentId=65f82ba030dcf.... Accessed: 26.11.2024 (in Russian).
Авторы
Konstantin K. Laktionov*1,2, Mikhail Fedyanin1,3,4, Daniil L. Stroyakovskiy5, Anastasiia S. Mochalova6, Aishat R. Iasieva7, Natal'ia V. Fadeeva8, Iuliia S. Shapovalova9, Oleg V. Mironov10, Aleksandr S. Dergunov11, Sergei V. Orlov12, Leonid A. Vasilev13,14, El'vira A. Bobrova15, Svetlana A. Orlova16, Antonina A. Kosukhina17, Natal'ia I. Polshina15, Sergei G. Vardanian4, Aleksei Iu. Fedoseev4, Karina Sh. Tumasian17, Anastasiia E. Danilova18, Tatiana V. Krashikhina19, Ekaterina I. Tsygankova20, Dmitrii E. Staritsyn21, Ol'ga V. Toporkova10, Mira V. Boskhomdzhieva22, Alexander V. Sultanbaev23,24, Margarita V. Edamenko17, Vadim N. Dmitriev17, Aleksandr V. Shkradiuk25, Konstantin A. Shkret26, Oxana N. Prosianikova27, Evgeny V. Svechnikov27, Semyon Yu. Grigorchuk27
1Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2Pirogov Russian National Research Medical University (Pirogov University), Moscow, Russia;
3Pirogov National Medical and Surgical Center, Moscow, Russia;
4Moscow Multidisciplinary Clinical Center „Kommunarka“, Moscow, Russia;
5Moscow City Oncology Hospital No. 62, Moscow, Russia;
6Medsi group JSC, Moscow, Russia;
7Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department, Moscow, Russia;
8Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, Chelyabinsk, Russia;
9Clinical Hospital “RZD-Medicine” of Chelyabinsk, Chelyabinsk, Russia;
10Tambov Regional Oncologic Clinical Dispensary, Tambov, Russia;
11Tver Regional Clinical Oncologic Dispensary, Tver, Russia;
12Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia;
13Current Medical Technologies JSC, St. Petersburg, Russia;
14Institute of Modern Medical Technologies, St. Petersburg, Russia;
15Loginov Moscow Clinical Scientific Center, Moscow, Russia;
16Republican Clinical Oncologic Dispensary, Cheboksary, Russia;
17Belgorod Regional Oncologic Dispensary, Belgorod, Russia;
18City Polyclinic No. 106, St. Petersburg, Russia;
19Moscow Center for Rehabilitation Treatment LLC, Moscow, Russia;
20Sergiev Posad Hospital No. 2, Sergiev Posad, Russia;
21Severodvinsk City Clinical Hospital No. 2 of Emergency Medical Care, Severodvinsk, Russia;
22Timoshkaeva Republican Oncologic Dispensary, Elista, Russia;
23Republican Clinical Oncology Dispensary, Ufa, Russia;
24Bashkir State Medical University, Ufa, Russia;
25Efetov Crimean Republican Oncologic Clinical Dispensary, Simferopol, Russia;
26Central City Clinical Hospital No. 24, Ekaterinburg, Russia;
27BIOCAD JSC, St. Petersburg, Russia
*lkoskos@mail.ru
1Blokhin National Medical Research Center of Oncology, Moscow, Russia;
2Pirogov Russian National Research Medical University (Pirogov University), Moscow, Russia;
3Pirogov National Medical and Surgical Center, Moscow, Russia;
4Moscow Multidisciplinary Clinical Center „Kommunarka“, Moscow, Russia;
5Moscow City Oncology Hospital No. 62, Moscow, Russia;
6Medsi group JSC, Moscow, Russia;
7Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department, Moscow, Russia;
8Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, Chelyabinsk, Russia;
9Clinical Hospital “RZD-Medicine” of Chelyabinsk, Chelyabinsk, Russia;
10Tambov Regional Oncologic Clinical Dispensary, Tambov, Russia;
11Tver Regional Clinical Oncologic Dispensary, Tver, Russia;
12Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia;
13Current Medical Technologies JSC, St. Petersburg, Russia;
14Institute of Modern Medical Technologies, St. Petersburg, Russia;
15Loginov Moscow Clinical Scientific Center, Moscow, Russia;
16Republican Clinical Oncologic Dispensary, Cheboksary, Russia;
17Belgorod Regional Oncologic Dispensary, Belgorod, Russia;
18City Polyclinic No. 106, St. Petersburg, Russia;
19Moscow Center for Rehabilitation Treatment LLC, Moscow, Russia;
20Sergiev Posad Hospital No. 2, Sergiev Posad, Russia;
21Severodvinsk City Clinical Hospital No. 2 of Emergency Medical Care, Severodvinsk, Russia;
22Timoshkaeva Republican Oncologic Dispensary, Elista, Russia;
23Republican Clinical Oncology Dispensary, Ufa, Russia;
24Bashkir State Medical University, Ufa, Russia;
25Efetov Crimean Republican Oncologic Clinical Dispensary, Simferopol, Russia;
26Central City Clinical Hospital No. 24, Ekaterinburg, Russia;
27BIOCAD JSC, St. Petersburg, Russia
*lkoskos@mail.ru
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