Final data on the eﬃcacy of the FORA study (FOrteca Real practice Assessment): a multicenter prospective observational study on the real-world eﬃcacy of prolgolimab in patients with metastatic melanoma in Russia
Authors: Orlova Kristina V. , Fedyanin Mikhail , Simanenkov Konstantin E. , Dergunov Aleksandr S. , Goldshmidt Petr R. , Saydullaeva Aleksandra F. , Bogacheva Darya V. , Yavorskaya Marina A. , Azanov Artur Z. , Fedenko Alexander A. , Bolotina Larisa V. , Deshkina Tatyana I. , Babina Kseniya G. , Kuzevanova Ekaterina A. , Zhukova Liudmila G. , Feoktistova Polina S. , Polshina Natalya I. , Peganova Ekaterina V. , Shikina Valentina E. , Sobolev Maksim M. , Mironov Oleg V. , Vaschenko Vera A. , Ershova Mariya M. , Mezhueva Agniya O. , Orlova Svetlana A. , Tantsyrev Denis A. , Taskina Darya K. , Teterich Antonina A. , Karabina Elena V. , Kostalanova Yuliya V. , Bogacheva Marina V. , Zhukova Natalia V. , Orlova Rashida V. , Zinkevich Maksim V. , Kazmin Aleksandr I. , Volkonskiy Mikhail V. , Voronkova Liya M. , Karpova Anastasiya S. , Maleyko Mikhail L. , Gorshenina Mariya N. , Kryuchkova Elena I. , Moiseenko Fedor V. , Murzina Yuliya I. , Musin Shamil I. , Ogloblin Andrey N. , Perminova Mariya S. , Dumbrava Regina A. , Emelyanov Sergey A. , Protsenko Svetlana A. , Sultanbaev Alexander V. , Tarasova Anna V. , Shakhnovich Elena B. , Demchenkova Marina V. , Lozovskaya Yuliya A. , Musaeva Khedi S. , Pavlova Elena M. , Skotnikov Roman A. , Chernova Vera V. , Chichkanova Angelina S. , Akhmatova Adina M. , Zafirova Marina A. , Mischenko Andrey A. , Ovsienko Elena N. , Petrukhnenko Viktoriya A. , Syusyukaylova Oksana A. , Tyugina Yana A. , Shumilkina Elena A. , Stroyakovskiy Daniil L. , Yurchenkov Aleksandr N. , Baldin Pavel L. , Belova Anastasiya S. , Diduk Olga V. , Konovalova Elena A. , Lebedeva Lyudmila N. , Li Yaroslav A. , Mashtapa Viktoriya V. , Mironenkova Yana A. , Narovenkova Kristina V. , Pavlikova Olga A. , Parsadanova Elvira L. , Pimonova Irina S. , Ruzhnikova Anna A. , Sivunova Irina D. , Soloveva Ekaterina P. , Sosnin Maksim I. , Temirsultanova Kh. Toita , Tyulegenova Makhabbat Zh. , Khodkevich Aleksandra V. , Shakurova Nadezhda R. , Efendieva Sureya N. , Avagimyan Karine L. , Anokhina Ekaterina Р. , Antoshkina Mariya I. , Borzyanitsa Stanislav M. , Dzhentemirov Samir K. , Dmitrochenko Marina V. , Zheleznyak Alla V. , Komoza Yuliya V. , Kopanev Aleksandr S. , Kornienko Tatyana I. , Krasilnikova Margarita A. , Lukhmanova Darya A. , Mazur Natalya S. , Markina Polina M. , Mitapov Zhargal S. , Osodoeva Svetlana N. , Prokopenko Irina A. , Radyukova Irina M. , Ramazanova Madina S. , Safarova Alfiya R. , Safronova Mariya A. , Khabrieva Khalimat M. , Tsygankova Natalya S. , Chermakova Kseniya V. , Chirkova Tatyana A. , Samoylenko Igor V. , Nazarova Valeria V. , Akhmetyanova Angelina E. , Demidov Lev V. 
Published: April 2024

Background. Prior to the introduction of new agents — immune checkpoint inhibitors — for inoperable and/or metastatic melanoma (IMM), chemotherapy outcomes were generally poor. The median (Me) overall survival (OS) in IMM was no more than 6-9 months, and the Me of progression-free survival (PFS) was about 2 months. The introduction of immune checkpoint inhibitors and targeted therapy changed the prognosis for the life of IMM patients dramatically. The development, studies, and approval of a new original PD-1 inhibitor, prolgolimab, in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess its real-world efficacy and safety.
Aim To evaluate the real-world efficacy and safety of prolgolimab in patients with IMM.
Materials and methods. From October 2020 to October 2022, 700 patients with IMM receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation were included in the study. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma; metastatic and/or inoperable type; use of prolgolimab outside of clinical trials; and signed informed consent. Objective response rate in the general population and the Intention-to-treat and Per Protocol populations was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 3-4 adverse events (AEs). PFS and OS rates were also assessed. Statistical analysis was performed using the SPSS 25.0 software package.
Results. The objective response rate for the Per Protocol population (with radiographic assessment available) was 42% (n=235/559). Disease progression was reported in 26.7% (n=149) of patients, stabilization in 31.3% (n=175), and disease control in 73.3% of patients with IMM, regardless of the line of therapy. At the follow-up Me of 12 months (0-36), PFS for all patients regardless of the line of therapy was 8 months (95% confidence interval [Cl] 6.537-9.463), 6-month PFS was 55%, and 12-month PFS was 41%. OS Me for all included patients was 32 months, 6-month OS was 82%, and 12-month OS was 69%. Depending on the line of therapy, the OS Me was: line 1 - not reached, line 2-30 months (95% Cl 16.007-43.993), line 3 and subsequent- 22 months (95% Cl 14.264-29.736); p=0.736. According to the CTCAE 5.0 general terminology criteria for AEs, a total of 136/693 (19.6%) AEs of varying degrees were reported, in particular: grade 1-2 - 105/693 (15.2%), grade 3-4 - 25/693 (3.6%), unknown grade - 5/693 (0.7%), as well as one fatal case (0.1%) due to thromboembolism in the vascular center with an unclear (according to the investigator's assessment) relation with prolgolimab.
Conclusion The results obtained at 12 months of follow-up confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with IMM in real-world practice, regardless of the line of therapy and other characteristics.