Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis

Abstract

Introduction

Lung cancer is one of the most common fatal solid malignancies worldwide and the leading cause of death (1). Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancers (2). Over the past 20 years, research on immunobiology and cancer immune checkpoint blocking therapies has stimulated further interest in immunotherapy for NSCLC (3–5). Immune checkpoint inhibitors (ICIs) have become the 1st-line therapy for a variety of malignant tumors, adding immunotherapy to the ranks of surgery, chemotherapy, radiotherapy, and targeted therapy (6, 7). Atezolizumab is currently regarded as an effective treatment option for NSCLC (8), and its mechanism of action is different from other inhibitors; this kind of monoclonal antibody directly binds to programmed cell death ligand 1 (PD-L1), promoting double blockade of B7 and programmed cell death protein 1 (PD-1) receptors, thereby restoring anticancer immunity (9). The results of many large-scale randomized controlled trials (RCTs) based on atezolizumab in NSCLC patients have confirmed the concept of a durable anti-tumor response and improved overall survival (OS) and progression-free survival (PFS) (10).

However, only a few individuals (15%–25%) have observed a survival benefit, and most individuals have primary or acquired resistance to ICIs (11). Serious and life-threatening adverse events were observed in these patients. It is becoming even more urgent to explore suitable biomarkers to identify candidates for atezolizumab and achieve accurate treatment of NSCLC, both to protect individuals from ineffective treatment and to limit the number of individuals exposed to the potential autoimmune side effects of targeted axis drugs (12, 13).

To date, PD-L1 expression has emerged as the best-known and most commonly used biomarker to predict which patients are highly likely to respond to immunotherapy in NSCLC (14, 15). The association between atezolizumab and PD-L1 expression response has been explored in several NSCLC studies (16–18). Atezolizumab is more likely to benefit individuals with high levels of expression of PD-L1 reflected in tissue samples (19). Unfortunately, obtaining sufficient tumor tissue for molecular detection in individuals with advanced NSCLC is challenging. Furthermore, the lack of unification between various anti-PD-L1 clones and immunohistochemistry platforms and methodological issues, such as antibodies and positive thresholds for evaluating PD-L1 expression, are also difficult issues (13, 20, 21). Another predictive biomarker is the tumor mutation burden (TMB); high TMB has a clinical effect on atezolizumab in patients with NSCLC (22), but there is no consensus at present. Although CD8 + T cells and other emerging biomarkers have broad prospects, they also have some limitations (23–25).

It is important to identify other practical and economic factors to predict the potency of atezolizumab. There are differences in the role of atezolizumab in individuals with different clinical and molecular features (26). Therefore, we conducted this meta-analysis to determine the predictive value of various clinical and molecular attributes to guide the selection of individuals with NSCLC who would benefit from atezolizumab. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting checklist was used in the meta-analysis.

Methods

Results

Study Selection and Characteristics

A total of 573 potentially relevant records were identified from the databases and conferences as a result of the search strategy employed in the research. Figure 1 depicts the selection process, as well as the rationale for excluding studies deemed ineligible. A total of 566 studies were excluded after screening for their abstracts and full texts. Thus, 7 RCTs involving 4,859 individuals with advanced NSCLC were included in the meta-analysis (Table 1). These RCTs were published between 2016 and 2021 and were divided into the following categories: one of the studies was a clinical trial in phase II (18), and six were phase III trials (19, 27–36). Detailed risk of bias analysis revealed that the risk of bias in all RCTs was low (Figures 2, S1).

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Figure 1

PRISMA flow diagram.

Table 1

Basic characteristics of included studies.

Reference	Trial	Study phase	Stage	Treatment line	ICI used (n)	Control arm (n)	Histological type		Median(range) Age (years)	Male (%)	Never smokers (%)	Tumor PD-L1 expression			ECOG		Primary endpoint
							Squamous (%)	Non-squamous (%)				<1% (%)	≥1% (%)	Unknown (%)	0(%)	1 (%)
Fehrenbacher (18)	POPLAR	II	Advanced or metastatic	≥2L	Atezolizumab (144)	Docetaxel (143)	33.8	66.2	62.0 (36–84)	58.9	19.5	62	38	0	31.7	67.2	OS
Rittmeyer (27)	OAK	III	IIIB or IV	≥2L	Atezolizumab (613)	Docetaxel (612)	26.2	73.8	63.5 (25–85)	61.9	17	43.3	55.8	0.8	37.1	62.9	OS
Fehrenbacher (28)
Socinski (29)	IMpower 150	III	IV or recurrent metastatic	1L	Atezolizumab + carboplatin + paclitaxel (402)	Bevacizumab + carboplatin + paclitaxel (400)	0	100	63.0 (31–90)	60	19.9	48.8	50.5	0.7	42.2	57	PFS and OS
Reck (30)
Socinski (31)					Atezolizumab + bevacizumab + carboplatin + paclitaxel (400)
Nogami (32)
West (33)	IMpower 130	III	IV	1L	Atezolizumab + carboplatin + nab-paclitaxel (451)	Carboplatin + nab-paclitaxel (228)	0	100	64.3 (18–86)	58.9	9.6	52.4	47.6	0	41.2	58.5	PFS and OS
Jotte (34)	IMpower 131	III	IV	1L	Atezolizumab + carboplatin + nab-paclitaxel (343)	Carboplatin + nab-paclitaxel (340)	100	0	65.0 (23–86)	81.6	8	48.5	51.4	0.1	32.9	66.8	PFS and OS
Nishio (35)	IMpower 132	III	IV	1L	Atezolizumab (292)	Carboplatin or cisplatin plus pemetrexed (286)	0	100	63.5 (31-85)	66.4	11.6	28.2	31.3	40.5	41.5	58.1	PFS and OS
Herbst (19)	IMpower 110	III	IV	1L	Atezolizumab (107)	Chemotherapy (98)	24.4	75.6	64.4 (33-87)	69.8	11.7	0	100	0	35.6	64.4	OS
Jassem (36)

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Figure 2

Risk of bias graph.

Effects of Atezolizumab in NSCLC

Eight studies examined the efficacy of atezolizumab-based therapy in NSCLC compared with chemotherapy-based treatment. The comprehensive results showed that atezolizumab substantially enhanced OS (HR 0.82; 95% CI, 0.77–0.88; p < 0.00001) (Figure 3A). Seven investigations reported that atezolizumab-based therapy achieved PFS improvement in NSCLC patients compared to chemotherapy-based treatment (HR 0.72; 95% CI, 0.61–0.85; p < 0.0001) (Figure 3B). Based on the treatment regimens, atezolizumab combined with chemotherapy significantly prolonged patients’ PFS compared to chemotherapy alone; however, this survival benefit was not observed with atezolizumab monotherapy. In addition, a significant improvement in OS was observed with atezolizumab monotherapy or combination therapy (Figures 3C–F).

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Figure 3

Forest plots of HRs comparing (A) OS and (B) PFS between atezolizumab-based therapy and chemotherapy-based therapy, (C) OS and (D) PFS based on atezolizumab monotherapy, and (E) OS and (F) PFS based on atezolizumab combined therapy.

Effects of Atezolizumab by Age Group

Age group-specific survival data for individuals with NSCLC were presented in seven articles. In individuals aged <65 years (HR 0.82; 95% CI, 0.75–0.90; p < 0.0001) and those aged ≥65 years (HR 0.78; 95% CI, 0.67–0.90; p = 0.0006), atezolizumab-based therapy substantially increased OS relative to chemotherapy-based treatment. Interestingly, when the cutoff value of age was set at 65–74 years old and ≥75 years old, we discovered an OS benefit in individuals aged 65–74 years old (HR 0.84; 95% CI, 0.72–0.98; p = 0.02), while no OS benefit was observed in patients aged ≥75 years (HR 0.89; 95% CI, 0.66-1.19; p = 0.42) (Figure 4A).

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Figure 4

Forest plots of HRs comparing OS between atezolizumab-based therapy and chemotherapy-based therapy with respect to (A) age group, (B) gender, (C) histological type, (D) PS score, (E) smoking status, (F) liver metastases status, (G) EGFR mutation status, (H) race, (I) PD-L1expression, and (J) treatment line.

Subgroup analyses based on the treatment regimen showed that this factor did not affect the OS improvement with atezolizumab in individuals aged <65 years. Subgroup analyses based on the line of therapy showed that the combined HR of six studies in 1st-line therapy was 0.82 (95% CI, 0.73–0.91; p = 0.0003). Only one study was related to ≥2nd-line therapy, with an HR of 0.84 (95% CI, 0.70–1.01; p = 0.06). In addition, atezolizumab significantly improved OS in individuals aged 65–74 years old who received 1st-line combination therapy (HR 0.84; 95% CI, 0.72–0.99; p = 0.04), but not those in 1st-line monotherapy. However, no prolonged survival was observed in individuals aged ≥75 years regardless of 1st-line monotherapy and 1st-line combination therapy. (Table S1). For PFS data from four studies, atezolizumab-based therapy substantially enhanced survival compared with chemotherapy-based treatment in patients aged <65 years (HR 0.67; 95% CI, 0.59–0.76; p < 0.00001) and ≥65 years (HR 0.60; 95% CI, 0.50–0.72; p < 0.00001). Similarly, we observed PFS benefit in individuals aged 65–74 years old (HR 0.60; 95% CI, 0.49–0.73; p < 0.00001) and ≥75 years old (HR 0.62; 95% CI, 0.43–0.90; p = 0.01) (Figure S2A and Table S2).

Discussion

We used the most recent clinical data and sought to determine whether practical and economical clinical and molecular pathological markers are available, which can be used to predict the potency of atezolizumab and guide treatment options for populations that may benefit from atezolizumab in the field.

Preclinical and clinical data suggest that whether PD-L1 inhibitors are beneficial to elderly patients with NSCLC remains controversial (37–40). It is still unclear whether PD-L1 inhibitors, such as atezolizumab, will be used in elderly patients. In individuals aged ≥75 years, our results did not show that atezolizumab was more effective than chemotherapy-based treatment for OS. This may be due to the decline in immune system function in the elderly, which makes them unable to restore anti-tumor activity (39), and it may also be due to the vulnerability of elderly patients to more severe immune-related toxicity than young patients (41). Thus, caution should be exercised when using atezolizumab in patients aged ≥75 years. These results were similar to those of a meta-analysis by Elias et al., which showed that PD-1/PD-L1 inhibitors provided benefits in solid tumor individuals aged <65 and ≥65 years, but not in patients aged ≥75 years (42). It is noted that according to our results, early atezolizumab-based combination therapy is recommended for individuals aged <65 years. In individuals aged 65–74 years old, the potency of ≥2nd-line treatment based on atezolizumab needs to be further clarified.

Gender variables are known to affect both innate and adaptive immune responses (43). The effect of individual sex on the potency of atezolizumab in the treatment of NSCLC remains controversial (44–48). Our meta-analysis showed that OS and PFS were both improved in male and female individuals administered atezolizumab compared with those administered chemotherapy-based treatment. However, in women, we did not find a survival benefit in the ≥2nd-line based on atezolizumab. This may be the reason for the small size of these populations. Furthermore, 1st-line treatment is more effective in female patients, probably because of a more effective immune system and limited disease burden (19). Therefore, it is worth noting that in future studies, there is more concern about the potency of female patients in ≥2nd-line treatment based on atezolizumab.

The RCTs of IMpower130 and 131 have similar clinical characteristics and the same treatment regimens, with the exception of different histological types, while different OS results were observed; IMpower130 (non-squamous) achieved an OS benefit, but IMpower131 (squamous) did not. This difference in results intrigued us and indicated that histological type may be a non-negligible factor affecting the potency of atezolizumab. Our meta-analysis results showed that for individuals with non-squamous cell NSCLC, both OS and PFS were improved regardless of the treatment line or regimen. However, squamous cell NSCLC only benefits the ≥2nd-line and monotherapy based on atezolizumab in OS, but not in first-line or combination therapy. In terms of PFS, we did not observe enhanced survival in patients with squamous cell NSCLC. The reason may be that squamous NSCLC accounts for 20%–30% of all lung cancer tissue types, whose characteristics are different from those of non-squamous NSCLC, and its prognosis is more serious (49). In addition, individuals with squamous NSCLC are older, have a higher comorbidity burden, have a history of smoking exposure, and may have clinical characteristics of nephrotoxicity (8, 50); therefore, treatment is not as effective as non-squamous cell carcinoma. Additionally, we found that atezolizumab, as an effective treatment option for NSCLC, is not histologically restricted to ≥2nd-line treatment. Based on the results of our analysis, histological type does not seem to be an appropriate predictor for evaluating the potency of atezolizumab.

The introduction of ICIs significantly improved the prognosis of NSCLC patients but was limited to ECOG PS 0 or 1 (51). In our meta-analysis, both PS 0 and 1 patients administered atezolizumab achieved OS and PFS benefits compared with those administered chemotherapy-based treatment. Therefore, an ECOG PS of 0 or 1 does not seem to be an appropriate predictor for evaluating the potency of atezolizumab. Because most RCTs excluded individuals with poorer PS (PS ≥2), we could not study the effect of atezolizumab on the PS ≥2 population. A meta-analysis of 19 real-world clinical studies revealed that a poorer survival rate existed in individuals receiving immunotherapy with PS≥2 (52). If PS ≥2 predicts poor atezolizumab potency, it should be verified by RCTs in the future.

The potency of atezolizumab in various smoking statuses was also analyzed in our analysis, and it was found that the survival benefit of atezolizumab was observed in active or former smokers but not in those who had never smoked. Some studies have shown that in NSCLC, smokers have a favorable trend for ICIs compared with non-smokers (53–55), which is consistent with our results. This may be because smoking is thought to increase the mutation load in tumors, increasing the expression of carcinogenic neo-antigen, and thus activating an efficient anti-tumor immune response (56, 57). Preclinical and clinical studies have shown that higher mutation and neoantigen loads are related to long-lasting clinical benefits of immunotherapy (58–60). This may explain why molecular smoking characteristics are associated with atezolizumab potency in NSCLC. Therefore, smoking history is a powerful clinical biomarker for the choice of atezolizumab therapy.

Due to a particularly unfavorable prognosis in NSCLC patients with distant metastases (e.g., liver metastasis) (61–63), immunotherapy has become an important treatment option for these individuals at present. Our meta-analysis showed that PFS, but not OS, was a statistically significant benefit in individuals with liver metastases treated with atezolizumab. Notably, we further found that the improvement in PFS was mainly reflected in atezolizumab 1st-line combination therapy for liver metastases. For patients without liver metastasis, OS was improved, which is similar to the atezolizumab 1st-line combined chemotherapy, but not monotherapy. These results suggest that NSCLC patients with and without liver metastasis may benefit more from combination atezolizumab treatment. A previous study showed that PD-1/PD-L1 inhibitors plus chemotherapy can lower the risk of progression by 29% and the risk of death by 21% in patients with liver metastases (64). Shiroyama et al. found that NSCLC patients with liver metastases were significantly younger and had more metastatic sites and poorer baseline ECOG PS, and lung cancer patients with these characteristics also have poorer prognoses (65). Moreover, liver metastases usually demonstrate incomplete activation of CD8 + T cells (66), deficient activation of CD8 + T cells (67), CD4 + T-cell inactivation (68), and Kupffer cells-induced regulatory T-cell activation (16), which reduced the probability of atezolizumab responding to liver metastases and did not improve OS. Consequently, liver metastatic status may be a survival outcome-independent predictor in NSCLC individuals given with atezolizumab. In addition, the strategy of atezolizumab combination therapy can expand the range of patients who respond to immunotherapy and improve the quality of clinical response, which is more than the effect of monotherapy. In addition, there are no data based on atezolizumab as a 2nd-line treatment, which deserves further exploration.

The relationship between atezolizumab and driver mutations has long been a hot research topic. In this study, we discovered that EGFR mutation status was linked to the potency of atezolizumab-based therapy. Individuals with wild-type EGFR benefited from atezolizumab treatment, whereas those with EGFR mutations did not. The biological rationale behind the effect of EGFR mutation status on the benefit of atezolizumab may be related to the fact that EGFR-mutant NSCLC subpopulations have more active escape/resistance pathways, which may limit the efficacy of atezolizumab in this context (69). Additionally, in EGFR mutant NSCLC, it is possible that atezolizumab is ineffective due to the fact that, first, previous studies indicated that the expression of PD-L1 is substantially lower in EGFR mutant tumors than in EGFR wild-type tumors, resulting in defective response to atezolizumab therapy in EGFR mutant patients (70, 71). Second, individuals with EGFR-sensitive mutations were more common in non-smokers, and their TMB was substantially lower than those with wild-type EGFR, suggesting that TMB may be a contributing factor to the poor potency of atezolizumab in EGFR-mutant patients (72–75). Third, unlike wild-type EGFR patients, EGFR mutations affect anti-tumor immune responses by modulating factors that may be associated with tumor microenvironmental status (for instance, tumor-infiltrating lymphocytes, regulatory T cells, and exosome CD73) (76–78). Although individuals with EGFR mutations usually do not respond well to atezolizumab, some can benefit from immunotherapy. OS was improved in EGFR mutation-sensitive individuals (19DEL and L858R) after atezolizumab plus chemotherapy and bevacizumab treatment in IMpower150 (30). The association between EGFR mutation status and atezolizumab therapy response should be explored, and further studies of these mechanisms are needed to effectively predict survival and to provide a better personalized treatment for individuals with EGFR mutations in NSCLC.

Atezolizumab is widely used in clinical practice, and this information is essential to maximize the benefit to individuals with NSCLC. We found that only white patients achieved OS improvement with 1st-line combination therapy based on atezolizumab, while both Asian patients and Black or African Americans did not. In terms of PFS, we found that both Asian and white patients achieved survival improvement, but Black and African Americans did not. Given the analysis of subgroups, the results should be interpreted with caution because of the small number of individuals analyzed. Individuals with advanced NSCLC of different races have different clinical and genetic characteristics and socio-environmental makeup, which may influence their response to atezolizumab (79). It is possible that there is some yet unknown mechanism that could explain these differences, or it is far more likely that this statistical significance is due to chance. Therefore, further research and confirmatory studies with large numbers of patients applying atezolizumab-based therapy in different races, including ≥2nd-line therapy, are needed. Additionally, based on the results of our analysis, race can be used as a suitable predictor of atezolizumab.

The expression of PD-L1 in tumor cells assessed by immunohistochemistry is a crucial means to choose and stratify NSCLC individuals who could show better potency of checkpoint inhibitors (80). PD-L1 expression patterns in TC or IC have been discovered to possess potential clinical and biological relevance in NSCLC, and their expression independently attenuates anti-tumor immune function (80, 81). Our analysis results show that NSCLC patients with PD-L1-negative expression (TC0 and IC0) can have improved OS from atezolizumab, and we recommend that these patients use atezolizumab as a 1st-line monotherapy. Therefore, even for PD-L1-negative individuals, atezolizumab treatment is a good treatment option for such patients. Although individuals with low levels of PD-L1 expression (TC1/2 or IC1/2) could benefit from PFS after atezolizumab-based therapy (HR = 0.66; 95% CI, 0.56–0.77; p < 0.00001), there was no significant difference in OS results compared with chemotherapy-based treatment (HR = 0.83; 95% CI, 0.65–1.06; p = 0.13), which may be due to the fact that PFS benefits did not translate into OS benefits, which may be an inherent limitation of the experiments involved because of the risk of systematic bias and confounding factors, such as differences in the performance of different PD-L1 assays (82), or may be because PD-L1 expression did not take into account other interferences that inhibit the immune response to tumor cells, such as regulatory lymphocytes and bone marrow-derived suppressor cells (83), all of which resulted in the finding that OS did not benefit in this kind of population. When we performed a sensitivity analysis of patients with TC1/2 or IC1/2, excluding IMpower132, the 1st-line monotherapy based on atezolizumab, we unexpectedly observed a significant OS benefit after applying atezolizumab. Therefore, since there is only one monotherapy study based on atezolizumab and the evidence is insufficient, atezolizumab combination therapy should be prioritized in these patients. Furthermore, according to our results, for NCSLC patients with positive PD-L1 expression (TC1/2/3 or IC1/2/3), although OS was improved regardless of the treatment line and treatment regime, we did not find that atezolizumab, as ≥2nd-line treatment, improved patients’ PFS. Therefore, according to our in-depth analyses of Tables 2 and S3, we strongly recommend 1st-line atezolizumab combination therapy for these patients. Following this, an enhanced OS and PFS benefit was observed in the high-level expression of PD-L1 (TC3 or IC3) regardless of the treatment line or regimen. Studies have shown that atezolizumab has a long-lasting clinical response in individuals with advanced NSCLC with high levels of PD-L1 expression on TC or IC, which supports our findings (80, 81). Our analysis results also showed that TC2/3 or IC2/3 patients with NSCLC could obtain OS improvement from atezolizumab, and we recommended that these patients should use atezolizumab for ≥2nd-line monotherapy. Thus, PD-L1 expression can be considered as a suitable biomarker for atezolizumab-based therapy. A full understanding of the association between PD-L1 expression and the therapeutic effect of atezolizumab is conducive to the better selection of detailed regimens and improvement of the individualization of treatment.

In addition, although our results suggest that the treatment line cannot be used to predict the potency of atezolizumab, both 1st-line and ≥2nd-line treatments achieved OS improvement. However, the ≥2nd-line treatment subgroup seemed to have a better OS benefit (HR, 0.84; 95% CI, 0.77–0.90; for 1st-line; HR, 0.79; 95% CI, 0.70–0.90; for ≥2nd-line therapy). However, previous studies have shown that the treatment line could be deemed an appropriate predictor in PD-1/PD-L1 inhibitor therapy, and the 1st-line treatment subgroup has a better OS benefit. They believe that previous traditional chemotherapy or radiotherapy may produce potential immunosuppression and serious adverse reactions, which may have a negative impact on future immunotherapy (84). Inconsistent with our analysis, these contradictory findings may be the result of a combination of PD-1 and PD-L1 inhibitors, while our results specifically focused on the potency of atezolizumab in individuals receiving different treatment lines. In atezolizumab 1st-line therapy, the coverage of those who benefited from combination therapy was broader, while monotherapy benefits were observed only in patients with PS 0, TC0, and IC0. Some studies have shown that chemotherapy and ICI given at the same time may improve the anti-tumor effect of ICI. The immunogenic effect of chemotherapy is explained by several proposed mechanisms: the cytotoxicity of chemotherapy leads to the shedding of tumor antigen and an increase in dendritic cell antigen cross-presentation, and changes in the immune regulatory system lead to the proliferation of effector T cells, inhibition of regulatory T cells, and enhanced innate immunity (85–88). There are few studies and data related to ≥2nd-line combination therapy and insufficient evidence; therefore, it is worth paying close attention to the efficacy of atezolizumab ≥2nd-line combination therapy in subsequent studies.

It is of great concern to explore the molecular and immune mechanisms of atezolizumab and reveal the reasons why these patients may get or lack benefit from atezolizumab treatment, which is a great challenge for research in the field of cancer treatment in the future and also helpful for personalized treatment in the future. Although our research yielded useful insights, we acknowledge that this study has some limitations. First, these data were extracted from pooled data rather than from individuals in the trials, leading to selection bias. Second, different clinicopathological features, such as smoking status and EGFR mutations, may be associated with each other, causing confounding bias. While we are mainly concerned with a single trait, other confounding variables may affect survival outcomes. Third, since our study was based on correlation rather than causal findings, further research is required to comprehend the mechanisms by which different clinical and molecular features can predict atezolizumab potency, and to determine whether other biomarkers are associated with atezolizumab potency. The open-label design used in the included studies was another limitation, which may have led to potentially biased OS and PFS results.

From our meta-analysis, in NSCLC individuals, age group, smoking status, liver metastasis status, EGFR mutation status, race, as well as expression of PD-L1 can predict the potency of atezolizumab in individuals aged <65 years old and 65–74 years old, active or previous smokers, those without liver metastasis, those with EGFR wild-type, white individuals, and those with TC3 or IC3, TC2/3 or IC2/3, TC1/2/3 or IC1/2/3, as well as TC0 and IC0, all of whom may benefit from atezolizumab treatment. Atezolizumab can improve OS regardless of sex, histological type, ECOG PS performance status, and treatment line. According to subgroup analysis, male individuals, those with non-squamous NSCLC and PS 1, active or previous smokers, and those with wild-type EGFR, TC3 or IC3, and TC1/2/3 or IC1/2/3 could benefit from atezolizumab treatment not related to treatment line and treatment regimen.

In summary, specific clinical characteristics can be used to predict atezolizumab potency. These findings contribute to the practical application of atezolizumab in obtaining more accurate treatments for NSCLC. Subgroup analysis suggests that the appropriate population should be considered when selecting atezolizumab treatment to refine the choice of scheme and improve the individualization of treatment.

Data Availability Statement

The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.

Author Contributions

Conception and design: PC, WL, and GH. Collection and assembly of data: WL. Data analysis and interpretation: WL. Manuscript writing: WL and GH. Final approval of the manuscript: All authors. All authors contributed to the article and approved the submitted version.

Funding

This study was supported by funding from the Tianjin Major Disease Prevention and Control Science and Technology Project, Tianjin Municipal Science and Technology Bureau (18ZXDBSY00050).

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s Note

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References