A major outbreak of first-line immunization programs for advanced non-small cell lung cancer: single-agent, combined, and dual-immune programs each show their potential for lung cancer immunity review in 2021

*Only for medical professionals to read for reference
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There are evidence-based immunotherapy programs for advanced non-small cell lung cancer .

At this year's American Society of Clinical Oncology (ASCO) annual meeting, a number of immunotherapy studies announced the latest results
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At the conference, the problems of immune and chemotherapy resistance treatment strategies mainly involved three studies, namely nintedanib + docetaxel for second-line treatment of lung adenocarcinoma patients who have failed immune combined chemotherapy (Abstract No.
9033), and Pa Bolivizumab (Drug K) + second-line chemotherapy for PD-1/L1 monoclonal antibody resistance (Abstract No.
9073) and carrelizumab + chemotherapy sequential apatinib second-line chemotherapy failed non-small Cell lung cancer (NSCLC) (abstract number: e21051)
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So, what are the new advances in first-line immunotherapy for advanced lung cancer? Abstract 9000: Checkmate9LA two-year data update.
At the ASCO conference in 2021, studies involving advanced non-small cell lung cancer (NSCLC) first-line immunotherapy programs include Abstract 9000, Abstract 9001, Abstract 9016, Abstract 9034, Abstract 9060, Abstract 9085 , Abstract e21072, Abstract 9038, Abstract 9091, Abstract 9085, Abstract 9059, Abstract 9102
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So, which research directions do these studies represent for the first-line treatment of advanced NSCLC? Let's look at the next inventory
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In the results of the previously published Phase III randomized controlled study of CheckMate 9LA, for metastatic NSCLC without EGFR and ALK gene mutations, the first-line use of nivolumab (NIVO) + ipilimumab (IPI) Compared with the standard 4 cycles of chemotherapy, 2 cycles of chemotherapy significantly improved the patient's overall survival (OS), progression-free survival (PFS) and objective response rate (ORR)
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Here, we mainly update the efficacy and safety data of the study after 2 years of follow-up, to observe whether patients can benefit in a long-term, and the treatment is poor due to the use of nivolumab + ipilimumab + chemotherapy.
The post-event efficacy of patients who responded to the study interruption was analyzed
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CheckMate 9LA study design: Follow-up treatment of patients during the 2-year follow-up period 1 Update of the 2-year median OS of all randomized populations: NIVO+IPI+ chemotherapy group is better, patients with brain metastases can be used in the 2-year follow-up time, NIVO+IPI+ chemotherapy The median OS of the chemotherapy group and the chemotherapy group were 15.
8 months and 11.
0 months, respectively, P=0.
72 (0.
61-0.
86).
The 1-year OS rates of the two groups were 63% vs 47%, and the 2-year OS rates were 38%.
And 26%
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After 2 years of follow-up, the patient’s median OS time was longer than in the interim analysis
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The subgroup analysis showed that the OS benefit trend of patients with brain metastases was obvious, suggesting that the first-line treatment of NIVO+IPI+chemotherapy is feasible for patients with brain metastases
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In addition, patients who smoke are more likely to benefit from the NIVO+IPI+ chemotherapy regimen than non-smokers
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2 years OS update for all random populations.
OS subgroup analysis after 2 years follow-up time.
PFS, ORR and DOR after 22-year follow-up: NIVO+IPI+ chemotherapy group was higher and longer.
During the 2-year follow-up time, NIVO+IPI+ chemotherapy The median PFS of the chemotherapy group and the chemotherapy group were 6.
7 months and 5.
3 months, respectively [hazard ratio (HR) 0.
67 (0.
56-0.
79)], and the 1-year and 2-year PFS rates were 33% vs 19% and 20%, respectively vs 8%; ORR of the two groups was 38.
0% (137 cases) vs 25.
4% (91 cases), and the median duration of response (DoR) of the two groups was 13.
0 months vs 5.
6 months, 1 year and 2 years, respectively The proportion of patients with persistent treatment response was 52% vs 24% and 34% vs 12%, respectively
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Exploratory study results of PFS, ORR and DOR3 after 2 years of follow-up: The results of different studies on the effectiveness of patients with different PD-L1 expression are shown in the figure, suggesting that PD-L1 testing is required before clinical treatment
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Exploratory study results after 2 years of follow-up 4 Safety results: The incidence of treatment-related adverse reactions was higher in the NIVO+IPI+ chemotherapy group, but the rate of discontinuation was not high.
After 2 years of follow-up, any grade and ≥3 grade adverse reactions , NIVO+IPI+ chemotherapy group and chemotherapy group were 92 cases vs.
88 cases and 48 cases vs.
38 cases, respectively
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The number of patients discontinued due to treatment-related adverse reactions in the two groups was 17 vs 6 and 14 vs 3 in any grade and ≥3 adverse reactions, respectively
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The adverse effects of treatment in the NIVO+IPI+chemotherapy group mainly occurred in the first two courses of treatment
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The safety results of the two groups after 2 years of follow-up 5 The efficacy results of patients who discontinued the drug due to adverse reactions in the NIVO+IPI+ chemotherapy group.
In post-event analysis, the median OS of these patients was 27.
5 months, and the 2-year OS rate was 54% , ORR was 51% (31 cases), the median DoR after treatment interruption was 14.
5 months, and the proportion of patients who maintained treatment response after 1 year was 56%
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It shows that although treatment is interrupted, the treatment plan of NIVO+IPI+chemotherapy can continue to benefit patients
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Efficacy results for patients who discontinued the drug due to adverse reactions in the NIVO+IPI+chemotherapy group.
In summary, the results of the study show that even after a 2-year follow-up period, the treatment regimen of NIVO+IPI+chemotherapy has a survival benefit and curative effect compared to chemotherapy alone.
The benefits are better, and patients can continue to benefit
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This program may become the first-line treatment option for advanced NSCLC
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Abstract 9001: First-line treatment of 1%～49% of advanced NSCLC in PD-L1 combined with chemical immune vs.
immune, which is better? For advanced/metastatic NSCLC without driver gene mutations, after molecular and PD-L1 immunohistochemical tests have shown that the expression of PD-L1 is 1% to 49%, whether to choose immune combination chemotherapy or pure immunization The treatment is quite controversial
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Therefore, the team of Professor Oladimeji Akinboro from the US Food and Drug Administration (FDA) designed the study
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Data are collected from randomized controlled studies approved by the FDA for chemotherapy combined immunization and immunization alone for advanced/metastatic NSCLC with no driver gene mutations and PD-L1 expression of 1% to 49%
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After screening the research plan, the final chemotherapy combined immunization group was 639 patients, and the immunization alone group was 529 patients
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List of studies included in the study design 1 PD-L1 expression of 1% to 49% of the OS and PFS results of NSCLC patients: higher in the chemotherapy combined immunization group For PD-L1 expression of 1% to 49% of NSCLC patients, chemotherapy combined immunization and simple With immunotherapy, the patients’ median OS was 21.
4 months and 14.
5 months, respectively, and the HR (95%CI) was 0.
68 (0.
52, 0.
90)
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The same is true for the PFS results.
The median PFS of the two groups was 7.
7 months vs 4.
2 months, and the HR (95% CI) was 0.
60 (0.
48, 0.
76)
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PD-L1 expression is 1%～49% of NSCLC patients’ OS results, PD-L1 expression is 1%～49% of NSCLC patients’ PFS results 2PD-L1 expression is 1%～49% of NSCLC patients’ OS subgroup analysis results for PD -L1 expression is 1% to 49% of NSCLC patients.
The results of OS subgroup analysis show that for people over 75 years old, it is not very likely to benefit from OS from chemotherapy combined immunization
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In addition, patients with an ECOG score of 1 tended to benefit more than patients with a score of 0
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PD-L1 expression is 1% to 49% of NSCLC patients OS subgroup analysis results 3PD-L1 expression is 1% to 49% of NSCLC patients PFS subgroup analysis results for PD-L1 expression of 1% to 49% NSCLC patients, The results of the PFS subgroup analysis showed that non-smokers can benefit more from chemotherapy combined immunization with PFS.
In addition, patients over 75 years old are also difficult to get PFS benefit from chemotherapy combined immunization
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PD-L1 expression is 1% to 49% of the PFS subgroup analysis results of NSCLC patients.
In short, this is a retrospective clinical study with a certain degree of bias, and the safety results have not been analyzed
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However, for patients with PD-L1 with an ECOG score of 1 and an expression of 1% to 49% of NSCLC before the age of 65 to 74, they can benefit from OS and PFS from the immune combined chemotherapy regimen, but it cannot be considered as For people over 75 years old, immunotherapy combined with chemotherapy is less effective than immunotherapy alone
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Abstract 9016: The Checkmate227 4-year survival rate is updated again.
The Checkmate227 study included advanced/relapsed NSCLC without systemic treatment and without driver gene mutations.
For patients with brain metastases, brain metastases were not treated
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According to the expression of PD-L1, the patients were divided into two groups: PD-L1≥1% (1189 cases) and PD-L1<1% (550 cases), and the two groups were randomly divided according to a ratio of 1:1:1 Into the NIVO+IPI, chemotherapy and NIVO groups
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Checkmate227 study design 1 overall survival data: adenocarcinoma patients with PD-L1≥1%, overall patients with PD-L1≥50%, and squamous cell carcinoma patients with PD-L1<1% have more obvious OS benefits in non-squamous Among NSCLC patients, the NIVO+IPI group had greater OS benefit [NIVO+IPI vs chemotherapy HR (95%CI) 0.
81 (0.
67-0.
99)]
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In the population with PD-L1≥50%, the overall benefit was more obvious in the NIVO+IPI group compared to the NIVO+IPI group, the NIVO group, and the chemotherapy group.
The 3-year and 4-year OS rate was 43% vs 36 %vs 26% and 37%vs 26%vs 20% [NIVO+IPI vs chemotherapy HR is 0.
66 (0.
52-0.
84)
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In the population with PD-L1<1%, patients with squamous cell carcinoma who use NIVO+IPI have greater OS benefit [NIVO+IPI vs chemotherapy HR (95%CI) 0.
53 (0.
34-0.
84)]
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PD-L1 ≥ 1% of the population OS results PD-L1 ≥ 50% of the population OS results PD-L1 <1% of the population OS results 1DoR time: PD-L1 ≥ 50% of the population use NIVO+IPI treatment for the longest time for DoR In terms of PD-L1≥1%, PD-L1≥50% and PD-L1<1%, the median DoR time after treatment with NIVO+IPI was 23.
2 months (95%CI: 15.
5-33.
9) ), 31.
8 months (95%CI: 20.
7-51.
2) and 18.
0 months (95%CI: 12.
4-33.
2)
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DoR results after 4 years of follow-up 2 The efficacy results of patients who discontinued the treatment due to NIVO+IPI toxicity.
Post-mortem analysis showed that 66 patients (17%) in the population with PD-L1≥1% were due to the toxicity of NIVO+IPI.
The response resulted in interruption of treatment, and the 3-year and 4-year OS rates of this group of people were higher than all randomized people using NIVO+IPI, 48% vs 33% and 44% vs 29%, respectively, and the median OS was 30.
6 months , ORR was 53% (35 cases), the median DoR for discontinuation of treatment was 52.
6 months, and 53% of patients who had a treatment response more than 3 years after discontinuation of treatment
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In summary, the results of the 4-year OS results of the Checkmate227 study were updated for the first-line treatment of advanced NSCLC.
The use of NIVO+IPI for the first-line treatment of advanced NSCLC has added strength to the results of PD-L1 ≥ 1% and PD-L1 ≥ 1%.
In the population with L1<1%, the 4-year OS rate of NIVO+IPI vs.
chemotherapy patients was 29% vs 18% and 24% vs 10%, and in the population with PD-L1 ≥ 1%, even with NIVO+IPI treatment Interruption, there are still about half of the patients with more than 3 years of treatment response
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Poster Abstract 9034 + Abstract 9060 + Abstract 9085: Summary Summary Abstract 9034 shows that atelizumab + bevacizumab + chemotherapy (carboplatin + pemetrexed) for the treatment of non-squamous NSCLC ORR is 35.
71%, 1 year PFS and OS was 55.
27% and 82.
90%, but 3 patients died, and this regimen should be used with caution; Abstract 9060 shows that PD-1/CTLA-4 double antibody + chemotherapy is the first-line treatment of NSCLC, with a median PFS of 5.
9 months (95%CI: 5.
3; 8.
7), the median OS has not yet been reached, the 12-month and 15-month OS rates are both 74.
9%, the ORR is more than 50%, and the disease control rate (DCR) is 87.
7%.
-L1≥1% and patients with squamous cell carcinoma have more prominent curative effect; Abstract 9085 shows that Cemiplimab single-agent first-line treatment of NSCLC has considerable brain control effect.
Patients with brain metastases treated with Cemiplimab single-agent, median OS is 18.
7 months, median PFS For 10.
4 months, the ORR was 41.
2%
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Especially for patients with PD-L1≥50% and stable baseline brain metastasis, Cemiplimab monotherapy is more obvious
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Abstract e21072 Study: Penpulimab combined with Anlotinib in the first-line treatment of advanced non-squamous NSCLC.
This is a study by the team of Professor Han Baohui from Shanghai Chest Hospital in China.
Penpulimab is a human-derived IgG1 monoclonal antibody directed against PD-1, which is specific It can eliminate the ADCC or CDC effect mediated by the Fc fragment of the receptor.
It has the characteristics of slow antigen-antibody binding-dissociation rate and high receptor occupancy.
Anlotinib is a multi-target TKI inhibitor.
In the phase III study of ALTER0303, it was shown that the overall survival of advanced NSCLC can be significantly prolonged.
Then, what about the combination of the two? This is the topic of this study
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As of January 13, 2021, a total of 26 non-squamous NSCLC patients with IIIB/IIIC/IV without driver gene mutations were enrolled in the study and were treated with Penpulimab (200mg Q3W) combined with Anlotinib (12mg QD), with a median treatment The duration is 3.
5 months
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The results of the study showed that the final 21 patients had at least one evaluable tumor lesion, the ORR was 57.
1%, and the DCR was 90.
5%.
The median PFS has not yet reached, and 11 patients who responded to treatment had sustained efficacy
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In terms of safety, treatment-related adverse reactions (TRAEs) occurred in 53.
8% of patients, which were generally controllable
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In short, for locally advanced/metastatic NSCLC, penpulimab combined with anlotinib is used in the first-line treatment, which has a clear curative effect and is safe and controllable, or it can provide a solution to chemotherapy for locally advanced/metastatic NSCLC
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Abstract 9038: KEYNOTE598 study-For patients with PD-L1 TPS ≥50% of metastatic NSCLC who used pembrolizumab (pembro) + IPI and pembro + placebo, a comparative study on the quality of life of patients Compared with pembro+placebo, pembro+IPI cannot prolong OS and PFS in patients with untreated metastatic NSCLC with PD-L1 TPS≥50% of driving gene mutations, and the incidence of adverse reactions is higher
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Here, the results (PRO) reported by the patients in the study are mainly reported
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The results of the study showed that as of September 1, 2020, for the PRO part of the KEYNOTE598 study, pembro + IPI and pembro + placebo enrolled 280 patients respectively
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The results showed that the average QLQ-C30 global health status/quality of life (GHS/QoL) scores during the follow-up period of the two groups were similar, and the least squares (LS) average value (95%CI) of the two groups from baseline to week 18 GHS/QoL both improved [pembro + IPI: 3.
7 (0.
9-6.
5); pembro + placebo: 4.
1 (1.
4-6.
9)], there was no significant difference between the groups
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The median time to elimination (TTD) for cough, chest pain, and dyspnea has not been reached in pembro + IPI, while pembro + placebo is 20.
0 months
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In short, for untreated metastatic NSCLC patients with PD-L1 TPS≥50% without driver gene mutations, the treatment regimens of pembro+IPI and pembro+placebo have no significant difference in health-related QoL and TTD
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Abstract 9091: A real-world study of first-line use of pembrolizumab in patients with PD-L1 TPS≥50% of advanced NSCLC: a French double vision multicenter study-ESCKEYP study This study aims to clarify that PD-L1 TPS≥50 % Of patients with advanced NSCLC use pembro's curative effect on the front line in the real world
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The results showed that the study included a total of 845 patients from 33 centers.
As of December 31, 2020, for the evaluable 783 patients, complete remission (CR), partial remission (PR), and stable disease (SD) The proportions of patients with disease progression were 4.
7%, 42.
6%, 24.
1%, and 28.
6%, respectively.
588 patients (69.
6%) discontinued pembro treatment, and 390 patients (66.
4%) had their first disease progression, of which 320 patients Patients (82.
1%) received second-line treatment, mainly platinum-containing chemotherapy (90.
6%)
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After a median follow-up of 25.
8 months, the median PFS and median OS were 8.
2 months and 22.
6 months, respectively.
The survival rates at 6, 12, and 18 months were 76.
8%, 64.
8%, and 54.
3%
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There were 835 adverse reactions in 48% of patients
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In short, although the screening of patients is not so rigorous, pembro as a single drug is similar to previous key clinical trials in terms of tumor shrinkage, PFS, and OS in patients
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Abstract 9085: Exploration of chemotherapy combined with immune checkpoint inhibitor therapy for NSCLC patients with driver gene mutations-a retrospective study of lung cancer from the University of California, researchers from the University of California reviewed NSCLC with driver gene mutations The results of studies on the treatment of patients with chemotherapy and chemotherapy + immune checkpoint inhibitors will be analyzed
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The results showed that a total of 125 patients were enrolled in the study, 70 and 55 were treated with chemotherapy and chemotherapy + immune checkpoint inhibitors, respectively.
The median PFS of the two groups was 225 days and 219 days (HR 1.
07, P=0.
72574) ), the median OS was 555 days and 553 days (HR 0.
80, P=0.
8655)
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Among the groups, only the KRAS mutation group and current/previous smoking patients received chemotherapy plus immune checkpoint inhibitor treatment with a median PFS that was numerically longer than the chemotherapy group
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In summary, for NSCLC with positive driver genes, the use of immune checkpoint inhibitors + chemotherapy compared with chemotherapy does not bring survival benefits in the overall population
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Abstract 9059: Exploration of using Cemiplimab as the first-line treatment for PD-L1≥50% of advanced NSCLC patients with brain metastases-EMPOWER-Lung 1 subgroup analysis results in the phase III EMPOWER-Lung 1 study, for PD-L1≥ In 50% of patients with advanced NSCLC, Cemiplimab brings significant survival benefits and acceptable safety to patients compared with chemotherapy
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It is worth noting that in the EMPOWER-Lung 1 study, patients with brain metastases at baseline were underrepresented in clinical trials.
However, an exploratory analysis of published single-cohort studies showed that immunotherapy is effective for this.
One patient group is beneficial
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Here, the researchers analyzed the population of patients with brain metastases in the EMPOWER-Lung 1 study
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The results of the study showed that before randomization, a total of 68/563 patients with stable brain metastases at baseline were randomized into the Cemiplimab group and the chemotherapy group according to 1:1, with similar median follow-up time
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According to the independent review committee's research, the median OS of patients in the Cemiplimab group and chemotherapy group was 18.
7 months vs.
11.
7 months, the median PFS was 10.
4 months vs.
5.
3 months, and the ORR was 41.
2% vs.
8.
8%
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During the course of treatment, 2 patients (5.
9%) and 4 patients (11.
8%) who were treated with Cemiplimab and chemotherapy developed central nervous system progression, and 9 patients (26.
5%) and 15 patients (44.
1%) were treated with Cemiplimab and chemotherapy.
The patient has progression outside the central nervous system
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EMPOWER-Lung 1 study brain metastasis subgroup analysis results In summary, the study results show that for patients with PD-L1 ≥ 50% and brain metastases with advanced NSCLC, the first-line treatment of Cemiplimab brings more OS, compared with chemotherapy.
PFS and ORR benefit
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For such patients, Cemiplimab may be the preferred treatment
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Abstract 9102: For patients ≥65 years of age with advanced lung squamous cell carcinoma, tislelizumab + chemotherapy compared with chemotherapy as the first-line treatment-the RATIONALE307 study is well known that tislelizumab is a humanized monoclonal Antibody, with high affinity and specificity for PD-1, has shown anti-tumor activity in advanced lung cancer
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In response, the investigators conducted a phase III, multi-center, randomized open-label study (NCT03594747) to evaluate the safety and effectiveness of tislelizumab combined with chemotherapy in patients with advanced squamous NSCLC, just as before It is reported that tislelizumab can significantly improve PFS and significantly reduce the risk of progression
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Here, the study reports the results of a subgroup analysis of people 65 years and older
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The results of the study showed that a total of 127 patients with advanced lung squamous cell carcinoma aged ≥65 years entered the randomized study (group A and group B were tislelizumab + different chemotherapy drugs; group C was chemotherapy alone)
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Regardless of PFS, ORR, A and B groups are higher than C group
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In terms of safety, there were 33 (84.
6%), 44 (84.
6%), and 28 (82.
4%) TRAEs in the three groups of grade ≥3.
These safety results were similar to those of the group of ≥18 years of age
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In conclusion, combined immunization and chemotherapy can be used as the first-line treatment for various groups of patients with advanced NSCLC squamous cell carcinoma
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*This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform