Efficacy and safety of K drug combined with concurrent radiotherapy and chemotherapy: from the KEYNOTE-799 study

Author: Doctor Renxin This article is published by Yimaitong authorized by the author, please do not reprint without authorization
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The PACIFIC study established the standard treatment status of duvalizumab, an immune checkpoint inhibitor for PD-L1, in inoperable stage III non-small cell lung cancer (NSCLC) patients
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What is the efficacy and safety of the immune checkpoint inhibitor for PD-1-Pembrolizumab combined with concurrent radiotherapy and chemotherapy in locally advanced NSCLC? Recently, the relevant data of the KEYNOTE-799 study was announced at the 2021 ASCO annual meeting and simultaneously published in JAMA Oncology
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Research background: Approximately 25% of NSCLC patients are diagnosed as stage IIIa-IIIc, of which a considerable number of patients cannot receive surgical treatment
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For these patients, platinum-based chemotherapy combined with concurrent radiotherapy is the standard treatment, and the 5-year survival rate is 16% to 32%
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In 2018, the immune checkpoint inhibitor duvalizumab for PD-L1 was approved for patients who did not progress after concurrent radiotherapy and chemotherapy (PD-L1 ≥ 1% in the European approved population, and the entire population of patients in the United States) Maintenance treatment
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Pembrolizumab is an immune checkpoint inhibitor against PD-1.
First-line combined chemotherapy or monotherapy can bring lasting benefits to advanced NSCLC patients with negative driver genes
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This two-cohort, non-randomized controlled study aims to evaluate whether combining pembrolizumab on the basis of concurrent radiotherapy and chemotherapy can bring survival benefits to patients with inoperable stage III
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Research method: This is a non-randomized, global, open-label two-cohort clinical study, which included NSCLC patients ≥18 years of age confirmed by histopathology or cytopathology
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After PET-CT and cranial magnetic resonance examination, distant metastases were excluded.
The patient was staged IIIa, IIIb, or IIIc (based on the 8th edition of TNM staging) and had not undergone chest radiotherapy in the past
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Patients who meet the enrollment criteria are determined by the investigator to enter the following cohort: Cohort 1, squamous cell carcinoma/non-squamous cell carcinoma cohort, in this cohort, patients receive paclitaxel 200 mg/m2 combined with carboplatin (AUC=6), after one cycle of treatment , Changed to paclitaxel 45 mg/m2 combined with carboplatin (AUC=2), weekly treatment for 6 weeks, during which two cycles of pembrolizumab treatment (once every three weeks) and standard radiotherapy (total dose 60Gy) were synchronized; Cohort 2: Non-squamous cell carcinoma patients, pemetrexed (500 mg/m2) combined with cisplatin (75 mg/m2) and pembrolizumab (200mg), combined with radiotherapy (60Gy) in cycles 2 and 3
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After concurrent radiotherapy and chemotherapy, all patients received 14 cycles of pembrolizumab treatment until there was progressive or intolerable toxicity
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Efficacy assessments were conducted every 9 weeks for the first 54 weeks, and then every 12 weeks
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The primary endpoint of this study is the objective response rate (ORR), and the secondary endpoints are progression-free survival (PFS) and overall survival (OS)
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Research results: From November 2018 to July 2020, a total of 216 patients were enrolled in the KEYNOTE-799 study, and cohort 1 and cohort 2 enrolled 112 and 104 patients, respectively
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In the two cohorts, 58.
9% and 39.
2% of patients had PD-L1 expression ≥1%, respectively.
The median time from the first administration to the data cutoff in the two cohorts was 18.
5 months and 13.
7 months, respectively, and the duration of treatment was respectively 9.
1 months and 7.
7 months
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The ORR of cohort 1 was 70.
5% and the disease control rate (DCR) was 88.
4%; the ORR of cohort 2 was 70.
6%, and the DCR was 93.
1%.
The median duration of response (DOR) was not reached in both groups, and the 1-year DOR rates were respectively These are 79.
7% and 75.
6% (Table 1)
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Table 1 The ORR subgroup analysis of patients found that in cohort 1, PD-L1 <1% and> 1% of patients had ORRs of 66.
7% and 75.
8%, respectively; ORRs of patients with squamous cell carcinoma and non-squamous cell carcinoma were 71.
2%, respectively And 69.
2%; the ORR of patients with stage IIIa and IIIb was 70.
7% and 73%, respectively
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In cohort 2, the ORRs of PD-L1<1% and >1% were 71.
4% and 72.
5%, respectively; the ORRs of IIIa and IIIb patients were 71.
8% and 69.
0%, respectively
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In the two cohorts, 28.
6% and 14.
7% of patients died, and the median OS was not reached.
The 1-year OS rate was 81.
3% and 87.
0%, respectively
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The median PFS was not reached, and the 1-year PFS rates were 67.
1% and 71.
6%, respectively
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Safety: 93.
8% and 97.
1% of patients in cohort 1 and cohort 2 had treatment-related adverse reactions (AEs) of any grade.
Among them, the incidence of AEs of grade ≥3 was 64.
3% and 50.
0%, and the most common ones were ≥3 Grade AEs were all pneumonia, with an incidence of 16.
1% and 9.
8%, respectively
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There were 4 cases and 1 case of patients in the two cohorts with fatal treatment-related adverse reactions.
Among them, cohort 1 was pneumonia, cohort 2 was interstitial lung disease, and 33.
9% and 18.
6% of patients in the two cohorts were due to AEs.
Lead to the termination of treatment
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In the two cohorts, 45.
5% and 40.
2% of patients had immune-related adverse reactions (irAE), of which the incidence of irAE ≥3 was 14.
3% and 8.
8%, respectively (Table 2)
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Table 2 Two-cohort irAE study conclusion: This non-randomized, two-cohort study found that pembrolizumab combined with concurrent radiotherapy and chemotherapy has good anti-tumor activity in inoperable stage III NSCLC patients
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Reference: Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non–Small Cell Lung Cancer The Phase 2 KEYNOTE-799 Nonrandomized Trial.
JAMA Oncol.
Published online June 4, 2021.
doi:10.
1001/jamaoncol.
2021.
2301