First results of a multicenter, non-randomized, prospective phase II study of the efficacy and safety of induction therapy with pembrolizumab, cisplatin, and 5-fluorouracil in patients with unresectable squamous cell carcinoma of the oropharynx, hypopharynx and larynx

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Background. The approved regimen of induction chemotherapy with docetaxel + cisplatin + 5-fluorouracil has high risk of unacceptable toxicity for many patients with advanced head and neck cancer (HNSCC). Toxicity can also compromise the delivery of the following chemoradiation. In order to improve the results of these pts treatment we conducted a prospective multicenter non-randomized phase II study of induction immunochemotherapy followed by (chemo)radiation and here we report first results of objective response rate (ORR), the safety profile of induction therapy and risk of further radiation therapy omission (NCT05551767).

Materials and methods. The inclusion criteria were: unresectable stage III–IVA cancer of larynx, oropharynx, hypopharynx, PD-L1-positive (CPS≥1) squamous cell cancer, ECOG 0-2. Included pts received 3 cycles of pembrolizumab 200 mg d1+ cisplatin 100 mg/m2 d1 + 5-fluorouracil 1000 mg/m2/day 1-4 d followed by (chemo-) radiation.

Results. Since January 2022 a total of 120 pts were included. Median age was 60 (35–75), the majority were male (105; 87.5%). Objective responses were assessed in 116 of 120 pts. ORR on induction phase was 62.9% (n=73), including 16.4% (n=19) of complete responses. Median change of target lesions was -55% (from -100% to 65%). To date, only 7 pts did not start (chemo)radiation in time due to disease progression (4 pts) or refuse of consent (3 pts). Among 95 pts who completed radiation therapy 94.7% received radiation dose ≥66Gy. The incidence of grade 3-4 adverse events was 30,8%, in 6 (5%) pts it required hospitalization. No grade 5 adverse events were observed. The most common toxicity was hematological with neutropenia grade 3-4 in 28 (23.3%) pts. There was mild immune-related toxicity: 2 (1.7%) pts had skin rash and 1 (0.8%) – hypothyroidism. The use of high dose of cisplatin resulted in a trend to decline glomerular filtration rate (median decrease was 10.5% from baseline) although none of pts required hemodialysis.

Conclusion. Induction therapy with pembrolizumab plus cisplatin and 5-fluorouracil provided meaningful ORR and acceptable safety profile in locally advanced HNSCC. It almost did not influence the following radiation therapy omission rate. Further follow-up is needed to assess long-term efficacy.

作者简介

Olesia Stativko

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

编辑信件的主要联系方式.
Email: olesya_stativko@mail.ru
ORCID iD: 0009-0002-1084-1551
SPIN 代码: 3627-0262

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

俄罗斯联邦, Moscow

Ilya Pokataev

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

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0001-9864-3837
SPIN 代码: 7338-9428

D. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"

俄罗斯联邦, Moscow

Sergey Kravtsov

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

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0002-0681-8976

D. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"

俄罗斯联邦, Moscow

Liudmila Zhukova

Loginov Moscow Clinical Scientific Center

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0003-4848-6938

D. Sci. (Med.)

俄罗斯联邦, Moscow

Daniil Stroyakovskiy

Moscow City Oncology Hospital №62

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

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Emil Sabitov

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

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0009-5110-2457

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

俄罗斯联邦, Moscow

Evgeniya Kuzmina

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

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0007-2856-5176
SPIN 代码: 9668-5733

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

俄罗斯联邦, Moscow

Polina Feoktistova

Loginov Moscow Clinical Scientific Center

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0002-0340-7119
SPIN 代码: 9638-4788

Cand. Sci. (Med.)

俄罗斯联邦, Moscow

Tatiana Antonova

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

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0007-6646-7454

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

俄罗斯联邦, Moscow

Marina Lyadova

Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department; Russian Medical Academy of Continuous Professional Education

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0002-9558-5579
SPIN 代码: 8220-2854

Cand. Sci. (Med.), Novokuznetsk State Institute for Further Training of Physicians, Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"

俄罗斯联邦, Moscow; Novokuznetsk

Margarita Nosova

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

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0003-0622-2528

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

俄罗斯联邦, Moscow

Rozana Sydykova

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

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0002-5569-3655

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

俄罗斯联邦, Moscow

Kristina Lisitsyna

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

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0002-6817-4907

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

俄罗斯联邦, Moscow

Tatiana Strelnikova

Moscow City Oncology Hospital №62

Email: olesya_stativko@mail.ru

oncologist

俄罗斯联邦, Moscow

Gulnara Alizade

Loginov Moscow Clinical Scientific Center

Email: olesya_stativko@mail.ru

oncologist

俄罗斯联邦, Moscow

Sergey Parts

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

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0003-9954-4584
SPIN 代码: 1350-6713

Cand. Sci. (Med.), Moscow State Budgetary Healthcare Institution "Oncological Center No. 1"

俄罗斯联邦, Moscow

Magomed Dolov

Moscow International Cancer Center

Email: olesya_stativko@mail.ru
ORCID iD: 0009-0004-5039-7875

radiotherapist

俄罗斯联邦, Moscow

Anna Tedeeva

Moscow International Cancer Center

Email: olesya_stativko@mail.ru

Department Head

俄罗斯联邦, Moscow

Vsevolod Galkin

Moscow City Hospital named after S.S. Yudin, Moscow Healthcare Department; Sechenov First Moscow State Medical University (Sechenov University)

Email: olesya_stativko@mail.ru
ORCID iD: 0000-0002-6619-6179

D. Sci. (Med.), Prof.

俄罗斯联邦, Moscow; Moscow

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2. Fig. 1. CONSORT standard chart of the distribution of patients included in the study.

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3. Fig. 2. Histogram of the depth of effects during induction CT (the percentage change in the sum of the measured foci in comparison with the initial radiological assessment is provided).

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