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Abstract

Introduction:

Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy as monotherapy in patients with pulmonary sarcomatoid carcinoma (PSC). We performed the current multi-institutional, real-world study to assess the efficacy of ICIs plus chemotherapy in patients with PSC.

Methods:

All consecutive patients with locally advanced or metastatic PSC from three centers treated with ICIs between January 2018 and July 2021 were enrolled. Programmed death ligand 1 (PD-L1) expression was stained and evaluated using immunohistochemical with 22C3. Single-cell RNA sequencing (scRNA-seq) was performed in two patients with PSC and two patients with adenocarcinoma to understand the cell-type-specific transcriptome landscape of cancer cells and tumor microenvironment (TME) of PSC.

Results:

A cohort of 42 PSC patients was identified. In the overall population, the objective response rate (ORR) was 73.8%, median progression-free survival (mPFS) was 10.3 months and median overall survival was not reached and 2-year survival rate was 51.2%. For 34 treatment-naïve patients who received first-line ICIs plus chemotherapy, the ORR was 70.6%, mPFS was 10.3 months and 2-year survival rate was 57.8%. In patients with PD-L1 tumor proportion score (TPS) < 1%, 1–49%, and ⩾50%, the ORR was 33.3%, 72.7%, and 85.7% and mPFS was 6.0, 6.7, and 10.3 months, respectively. Notably, two patients with transformed PSC from lung adenocarcinoma after epidermal growth factor receptor-tyrosine kinase inhibitor treatment also responded well to ICIs plus chemotherapy. scRNA-seq revealed immune-cell-inflamed TME, lower intratumoral heterogeneity, and activated immune response pathway in PSC.

Conclusions:

Our study demonstrated remarkable efficacy of ICIs plus chemotherapy as first-line therapy for patient with locally advanced or metastatic PSC.

Keywords

chemotherapy immune checkpoint inhibitors PD-1/PD-L1 pulmonary sarcomatoid carcinoma tumor microenvironment

Introduction

Pulmonary sarcomatoid carcinoma (PSC) is a rare subset of non-small-cell lung cancer (NSCLC), characterized by poorly differentiated tumors with a component of sarcoma or sarcoma-like elements¹ and highly aggressive biological behaviors.^2–5 PSC has been reported to be associated with poor prognosis and low responsiveness to first-line chemotherapy, with an objective response rate (ORR) of 16.5% and overall survival (OS) of only 6.3 months.⁶ Therefore, developing novel therapeutic strategies to improve the dismal prognosis of patients with this malignance is in high demand.

Recent multi-omics analyses have revealed high programmed death ligand 1 (PD-L1) expression, high tumor mutational burden (TMB), and a T-cell-inflamed tumor microenvironment (TME) in PSC.^7–9 All these features define this group most likely to respond to immune checkpoint inhibitors (ICIs). Intriguingly, a recent, multi-institutional retrospective study found that the ORR was 40.5%, progression-free survival (PFS) was 4.89 months, and OS was 12.7 months in 37 French patients with PSC who received ICI monotherapy as second- or later lines therapy.¹⁰ Furthermore, another study conducted in Korea also elucidated the outstanding efficacy of ICIs as monotherapy in PSC, with an ORR of 49%, median PFS of 7.2 months, and median OS of 22.2 months.¹¹ All these findings support ICIs as a promising choice in patients with PSC.

To date, ICIs in combination with platinum-based chemotherapy have been standard of care first-line treatment in patients with metastatic NSCLC without actionable oncogenic drivers, regardless of PD-L1 expression.^12,13 Although prospective studies that directly compare ICI monotherapy and ICIs plus chemotherapy in first-line setting for patients with metastatic NSCLC are not available, several network meta-analyses reported that combination therapy confers an improved ORR and PFS compared with ICI monotherapy in patients with PD-L1 tumor proportion score (TPS) ⩾ 50% tumors.^14,15 Due to the impressive efficacy of ICIs plus chemotherapy in metastatic NSCLC and most of the patients with PSC have high PD-L1 expression,¹¹ to evaluate the efficacy of ICIs in combination with chemotherapy in PSC is of high clinical interest. Therefore, we performed the current multi-institutional real-world study to assess the efficacy of ICIs plus chemotherapy in patients with locally advanced or metastatic PSC.

Material and methods

Patients and data collection

Electronic databases of three participating cancer centers (Shanghai Pulmonary Hospital, Hunan Cancer Hospital, and Anhui Provincial Hospital) were systematically searched for patients diagnosed with PSC between January 2018 and July 2021. PSC was diagnosed according to the 2015/2021 World Health Organization classification of lung tumors.^1,16 Tumor stage was determined according to the 8th edition of TNM Classification for lung cancer.¹⁷ Only patients with locally advanced or metastatic PSC (stage IIIA/IIIB/IIIC, IV) treated with ICI-based therapy at least more than two cycles were enrolled. The electric medical records were retrospectively reviewed and detailed clinicopathologic characteristics, including gender, age, smoking history, Eastern Corporation Oncology Group performance status, diagnosis method, metastatic sites, oncogenic mutation status, regimens used in any line, and PD-L1 expression were extracted and collected. EGFR, ALK, ROS1, RET, KRAS, NRAS, PIK3CA, BRAF, MET exon 14 (METex14), and HER2 were routinely detected by multiplex real-time PCR (Amoy Diagnostics Co., Ltd, Xiamen, China). Next-generation sequencing was performed in four cases. PD-L1 expression was stained and evaluated using immunohistochemical with 22C3 pharmDx assay (Dako, Carpinteria, CA, USA). The TPS ⩾ 1% was defined as positive PD-L1 expression and TPS ⩾ 50% was defined as high PD-L1 expression.

The study was approved by the institutional review board of each participating centers and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.

Evaluation of therapeutic outcomes

Tumor assessments were performed by two experienced medical oncologist (FZ and YZ) per the Response Evaluation Criteria in Solid Tumors criteria 1.1,¹⁸ independently. Any disagreements were resolved by a third senior medical oncologist (CZ). PFS was defined as the time from initiation of ICIs to documentation of disease progression or death, whichever occurred first. Patients without disease progression or death were censored. OS was defined as the time from initiation of ICIs to the date of death from any cause or last follow-up in surviving participants.

Single-cell RNA sequencing

Single-cell RNA sequencing (scRNA-seq) was performed in two patients with PSC and two patients with adenocarcinoma to understand the cell-type-specific transcriptome landscape of cancer cells and TME of PSC. Tissue dissociation and single-cell suspension preparation, scRNA-seq library preparation, and generation of single-cell gene expression matrices were performed as previously described.^19,20 To assign one of the 11 major cell types to each cluster, we scored each cluster by the normalized expressions of the following canonical markers: plasma cells (CD79A, JCHAIN, MZB1, IGHG1), stromal cells (DCN, LUM, ACTA2, COL1A1), mast cells (TPSAB1, TPSB2, CPA3), monocytes (CD14, FCN1, FCGR3A, VCAN), macrophages (C1QA, MRC1, CD163), dendritic cells (CD1C, CD1E, FCER1A), B cells (MS4A1, CD79A, CD79), T cells (CD2, CD3D/E/G, TRAC, TRBC1), cancer cells (EPCAM, KRT8, CD24, SOX4), alveolar epithelial cells (SFTPB, SFTPC, ABCA3, LAMP3), and ciliated cells (FOXJ1, TPPP3, PIFO). Gene set enrichment analysis (GSEA) of both cancer cell and T cells was performed with the R package GSVA. Intratumoral heterogeneity (ITH) scores were based on copy number alterations (CNAs) (ITH_CNA) and gene expressions (ITH_GEX). The calculations of ITH scores were inspired by our previous study.¹⁹ More detailed procedures have been described in the Supplemental Materials.

Statistical analysis

Chi-square test or Fisher’s exact test was used to assess the distribution of the clinicopathological variables. PFS and OS curves were estimated by the Kaplan–Meier method and compared by log-rank test. Cox proportional hazards model was performed, and hazard ratio (HR) and 95% confidence interval (CI) were calculated to determine the survival differences. All of the statistical analyses were performed with Origin (2019b, OriginLab, Northampton, MA, USA), the SPSS statistical software (version 22.0, SPSS Inc., Chicago, IL, USA), and the R package (Version 1.4.1106). Plots were generated by GraphPad Prism (version 7, GraphPad Software Inc., San Diego, CA, USA) and Origin (2019b, OriginLab, Northampton, MA, USA). Two-side p < 0.05 was considered statistically significant.

Results

Patients’ characteristics

A cohort of 42 PSC patients was identified. The baseline characteristics are listed in Table 1. The median age was 64 years (range, 49–78 years). Most patients were males (78.6%, 33/42). The majority of patients were non-smokers (54.8%, 23/42). Most patients were diagnosed with percutaneous lung biopsy samples (69.0%, 29/42) and had stage IV diseases (88.1%, 37/42). Three (7.1%) patients had liver metastases, 9 (21.4%) had brain metastases, 21 (50.0%) had bone metastases, and 11 (26.2%) had adrenal metastases.

Table 1.

Baseline demographics and disease characteristics of the 42 PSC patients who received ICIs.

Characteristic	N = 42 (%)
Age
Median age (years, range)	64 (49–78)
<65 years	22 (52.4)
⩾65 years	20 (47.6)
Sex
Male	33 (78.6)
Female	9 (21.4)
Smoking history
Never smoker	23 (54.8)
Smoker	19 (45.2)
Diagnosis method
Percutaneous lung biopsy	29 (69.0)
Operation	3 (7.2)
Bronchial biopsy	6 (14.3)
Node biopsy	4 (9.5)
ECOG performance status
0	11 (26.2)
1	30 (71.4)
2	1 (2.4)
Disease stage
IIIA/IIIB/IIIC	5 (11.9)
IVA/IVB	37(88.1)
Distant metastasis at baseline
Brain	9 (21.4)
Bone	21 (50.0)
Liver	3 (7.1)
Adrenal	11 (26.2)
PD-L1 expression
<1%	5 (11.9)
1–49%	12 (28.6)
⩾50%	19 (45.2)
Not assessed	6 (14.3)
Mutational status
EGFR mutation	3 (7.1)
KRAS mutation	14 (33.3)
MET exon 14 mutation	3 (7.1)
Others	2 (7.1)
No mutations	20 (47.6)
Line of ICI treatment
First line	36 (85.7)
Second line	4 (11.1)
Third line or more	2 (4.7)
Type of ICI treatment
ICIs alone	4 (11.1)
Chemotherapy plus ICIs	37 (88.1)
Chemotherapy plus ICIs plus bevacizumab	1 (2.4)

ECOG, eastern corporation oncology group; ICI, immune checkpoint inhibitors; PD-L1, programmed death ligand 1; PSC, pulmonary sarcomatoid carcinoma.

PD-L1 expression was assessed in 36 (85.7%) patients. Among these 36 patients, PD-L1-positive tumors (TPS ⩾ 1%) were identified in 31 (86.1%) patients and 19 (52.3%) patients had high PD-L1-expressing tumors (TPS ⩾ 50%). Regarding mutational status, three patients had EGFR mutations (2 had EGFR L858R point mutations, 1 had EGFR exon 19 deletion mutation), 14 had KRAS mutations, 3 patients had METex14 skipping mutations, and 2 patients had other molecular alterations (1 had RET fusion and 1 had BRAF^V600E mutation).

Six (14.3%) patients had received at least one previous systemic therapy, and 36 (85.7%) patients were treatment-naïve. In the first-line setting, two patients received ICI monotherapy, and 34 patients received ICIs in combination with chemotherapy. The detailed therapeutic regimens were listed in Supplemental Table 1.

ICI efficacy and clinical outcomes in overall cohort

The median follow-up was 16.6 months (interquartile range: 7.8–21.9 months). For the entire cohort, one patient had a complete response and 30 had a partial response. The ORR was 73.8%. Most patients (39/42, 92.9%) had a disease control and had a reduction in tumor size (Figure 1(a)). Responses were observed in both male and female patients, in patients who had brain metastases at baseline, and including in patients who had KRAS mutations, EGFR mutations, or METex14 skipping mutations. Treatment durations for each patient in the overall population are shown in Figure 1(b). The median PFS was 10.3 months (95% CI, 4.3–16.3 months) and median OS was not reached and 2-year survival rate was 51.2% [Figure 2(a) and (b)].

Figure 1.

Best percentage change in the tumor sum-of-diameters (a) and treatment durations (b) from baseline for the overall population.

Figure 2.

Median PFS and OS in overall population and first-line ICIs plus chemotherapy. (a) median PFS in overall population. (b) Median OS in overall population. (c) Median PFS in first-line ICIs plus Chemotherapy. (d) Median OS in first-line ICIs plus chemotherapy.

The efficacy of ICIs plus chemotherapy as first-line treatment

For 34 treatment-naïve patients who received first-line ICIs plus chemotherapy, one patient had a complete response and 23 had a partial response. Nine patients had stable disease and one patient had progressive disease. The ORR was 70.6%. The median PFS was 10.3 months (95% CI, 4.6–16.0 months) and the median OS was not reached and 2-year survival rate was 57.8% [Figures 2(c) and (d)].

For patients with PD-L1-expressing tumors (⩾1%), the ORR was 80%, median PFS was 10.3 months, and median OS was not reached. Meanwhile, for patients with PD-L1-negative (<1%) or unknown tumors, the ORR was 44.4%, median PFS was 6.0 months (PD-L1-positive versus negative/unknown: HR, 0.72, 95% CI, 0.24–2.16, p = 0.493), and median OS was 14.3 months (PD-L1-positive versus negative/unknown: HR, 0.73, 95% CI, 0.17–3.08, p = 0.633). When using PD-L1 TPS 1% and 49% as cutoffs, the ORR was 33.3%, 72.7%, and 85.7% in patients with PD-L1 TPS <1% population, PD-L1 TPS 1–49% population, and PD-L1 TPS ⩾50% population. While the median PFS was 6.0, 6.7, and 10.3 months (p = 0.861), respectively (Figure 3(a)). The median OS was not reached, not reached, and not reached (p = 0.510), respectively (Figure 3(b)).

Figure 3.

Median PFS and OS in first-line ICIs plus chemotherapy according to PD-L1 expression (a, b) and KRAS mutations (c, d).

In terms of mutational status, the median PFS was 11.7 months versus 6.5 months (HR, 0.59, 95% CI, 0.25–1.36, p = 0.231) in patients with and without KRAS mutations (Figure 3(c)). The median OS was not reached versus not reached (HR, 0.46, 95% CI, 0.14–1.51, p = 0.230) (Figure 3(d)) while the ORR was 76.9% versus 66.7%, respectively. Notably, in three patients harboring METex14 skipping mutations, two patients received pembrolizumab in combination with chemotherapy as first-line treatment (one had PD-L1 TPS 50% tumor and one had PD-L1-unknown tumor) and one patient received nivolumab monotherapy as fourth-line treatment (PD-L1 TPS <1%). Intriguingly, both of these two patients who received combination therapy in first-line therapy had a partial response and the treatment was still going on at the time of this article submission, 4.4 and 8.8 months after the treatment was initiated (Figure 1(b)).

ICIs plus chemotherapy in PSC transformation from lung adenocarcinoma after epidermal growth factor receptor-tyrosine kinase inhibitor treatment

In addition, in our cohort, two patients with EGFR sensitizing mutations (1 had EGFR L858R and 1 had EGFR exon 19 deletion) developed histologic transformation from adenocarcinoma to PSC after failure on previous epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment in subsequent biopsy (median PFS of previous EGFR-TKI treatment was 10.4 and 10.5 months, respectively) (Figure 4). Both of these two patients had PD-L1-positive tumors (PD-L1 TPS 25% and PD-L1 TPS 85%) after transformation and received ICIs in combination with chemotherapy as second-line therapy (Figure 4). Notably, they all responded well to the combination therapy and had a partial response (Figure 4). Furthermore, the response was durable and the median PFS was 8.6 and 14.0 months, respectively, and both were alive at the last follow-up (the median OS was 16.6 and 21.9 months, respectively).

Figure 4.

Two cases of ICIs plus chemotherapy in PSC transformation from lung adenocarcinoma after EGFR-TKI treatment. (a, g) HE staining of patients before administration of EGFR-TKI. (b, h) HE staining of patients after failure on EGFR-TKI treatment. (c, i) PD-L1 expression of patients after failure on EGFR-TKI treatment. (d, j) CT images before patients received ICIs plus platinum-based chemotherapy. (e, f) CT images of patient 1 after 6 and 10 months of treatment. (k, l) CT images of patient 2 after 3.6 and 8 months of treatment.

scRNA-seq of PSC

After quality control and filtering steps, a total of 5064 cells were analyzed. In all, 11 major cell types were detected by leveraging canonical cell markers, including plasma cells, stromal cells, mast cells, monocytes, macrophages, dendritic cells, B cells, T cells, cancer cells, alveolar epithelial cells, and ciliated cells. Interestingly, the proportions of cancer cells in PSC were lower than that in adenocarcinoma (Figure 5(a)). On the contrary, immune cells, including macrophages, monocytes, B cells, and dendritic cells, were enriched in PSC (Figure 5(a)). To further classify subgroups of immune cell types, six subtypes were identified according to canonical cell markers, including naïve T cells, CD8⁺ effector T cells, regulatory T cells, proliferating CD8⁺ effector T cells, macrophages and neutrophils. Again, although the distribution of immune cells was similar between PSC and adenocarcinoma, PSC had more immune cells in the TME (Figure 5(b)). Regarding ITH, PSC patients had numerically lower ITH_CNA and ITH_GEX scores compared to adenocarcinoma, although formal statistical analyses cannot be performed due to the sample size (Figure 5(c)). GSEA of cancer cells revealed the top 5 upregulated pathways in PSC (Figure 5(d)). Furthermore, antigen receptor-mediated signaling pathway was upregulated in PSC while basement membrane organization pathway was upregulated in adenocarcinoma (Figure 5(e)). GSEA of T cells, including naïve T cells, CD8⁺ effector T cells, proliferating CD8⁺ effector T cells, and regulatory T cells, revealed that antigen processing and presentation pathway and cytokine–cytokine receptor interaction pathway were the most common upregulated pathways in PSC (Figure 5(f)). GO analyses of T cells demonstrated that activation of immune response, adaptive immune response, or antigen receptor-mediated signaling pathway was upregulated in PSC (Figure 5(g)).

Figure 5.

scRNA-seq of PSC. (a) UMAP plot of 5064 cells from two patients with PSC and two patients with adenocarcinoma and major cell-type composition of each patient. (b) UMAP plot of immune cells and cell-type composition of each patient. (c) ITH scores based on CNAs (ITH_CNA) and gene expressions (ITH_GEX). (d) The top 5 enriched pathway of GSEA of cancer cells. (e) Antigen receptor-mediated signaling pathway was upregulated in PSC while basement membrane organization pathway was upregulated in adenocarcinoma. (f). The top 5 enriched pathway of GSEA of T cells, including naïve T cells, CD8⁺ effector T cells, proliferating CD8⁺ effector T cells and regulatory T cells and (g). GO analyses of T cells.

Discussion

The present, multi-institutional, real-world study demonstrated a profound efficacy of ICIs in patient with locally advanced or metastatic PSC. The overall ORR was 73.8%, median PFS was 10.3 months, and 2-year survival rate was 51.2%. In contrast to previous studies that evaluated ICI monotherapy in patient who were previously treated with platinum-based chemotherapy, 85.7% (36/42) of patients were treatment-naïve in our study. Intriguingly, in 34 treatment-naïve patients who received first-line ICIs plus chemotherapy, the ORR was 70.6%, median PFS was 10.3 months, and 2-year survival rate was 57.8%. Although the findings were attenuated due to its retrospective nature and small sample, our study, to the best of our knowledge, revealed encouraging efficacy of first-line ICIs in combination with chemotherapy in patients with locally advanced or metastatic PSC.

Due to the rarity of this malignance, prospective study that investigated the efficacy of ICIs in PSC is scarce. Two retrospective studies from French and Korea both demonstrated good efficacy of ICI monotherapy for PSC and revealed a positive correlation between PD-L1 expression and survival outcomes.^10,11 Babacan et al.²¹ performed a pooled analysis of published literature and five patients at Moffitt Cancer Center to investigate the efficacy of ICIs in patients with PSC. In 90 patients treated with ICI monotherapy, the ORR was 54.5%, and median PFS was 7.0 months. The positive PD-L1 expression rate was 90.4% (59/66). In patients with PD-L1-positive tumors, the ORR was 66.7% and median PFS was 14.4 months while the ORR was 28.6% and median PFS was 2.7 months in patients with PD-L1-negative tumors²¹. KCSG-LU16-07 was phase II study that investigated the efficacy and safety of durvalumab and tremelimumab for recurrent or metastatic PSC.²² The ORR was 26.7%, median PFS was 5.9 months, and median OS was 15.4 months.²² Taken together, all these studies elucidated good efficacy of ICI monotherapy or combination therapy for PSC and a positive correlation between PD-L1 expression and tumor response was also observed, despite the overall high PD-L1 expression in PSC.

On the basis of remarkable efficacy of ICI monotherapy in previously treated PSC, the efficacy of first-line ICIs in combination with chemotherapy in treatment-naïve PSC patients in our study may be not beyond expectation. In the all-comer trials of first-line ICIs in combination with chemotherapy in patients with lung adenocarcinoma and squamous cell carcinoma, the ORR ranges from 47.6% to 74.8%^12,13,23,24 and median PFS ranges from 5.1 to 11.3 months.^12,13,23,24 Overall, the response rate was higher and median PFS was longer in patients with high PD-L1-expressing tumors. Therefore, the high PD-L1 expression in PSC may, at least partially, led to the outstanding efficacy of ICIs plus chemotherapy in our study. Furthermore, immune-cell-inflamed TME, lower ITH scores and activation of immune response pathway in PSC, which have also been observed by scRNA-seq in our study, may also contribute to the good respond to ICI therapy.

Our study also observed promising efficacy of ICIs plus chemotherapy in PSC patient with METex14 skipping mutations. Previous studies have shown limited efficacy of ICI monotherapy in advanced NSCLC patients with METex14 skipping mutations.^25,26 Recently, three highly selective MET inhibitors, namely tepotinib, capmatinib, and savolitinib, have demonstrated substantial antitumor activity in advanced NSCLC with METex14 skipping mutations,^27–29 particularly in treatment-naïve patients.²⁸ In the future, as these three MET inhibitors have been approved for patients with METex14 skipping mutations, the role of ICIs plus chemotherapy deserves to be investigated, especially in those who have failed on MET-TKI therapy.

Another intriguing finding was that ICIs plus chemotherapy was effective in patients with transformed PSC from lung adenocarcinoma after EGFR-TKI treatment. Histologic transformation has been identified as an acquired resistance mechanism of EGFR-TKIs and lung adenocarcinoma with PSC transformation after EGFR-TKI treatment has also been observed in clinical cases.³⁰ The prognosis for patients with PSC transformation was poor after histologic transformation, with a median OS of 2.5 months in a previous study.³⁰ Notably, in their reported cases, one patient after PSC transformation received chemotherapy plus immunotherapy and the survival time was 16 months.³⁰ These findings also supported ICIs plus chemotherapy as a potential treatment option for patients with transformed PSC after EGFR-TKI treatment.

Our study has several limitations. First, this was a retrospective and small sample study, owing to the rarity of the disease. Furthermore, varied regimens, including different PD-1 antibodies and chemotherapy drugs, were included in the current study. Therefore, these findings, including scRNA-seq results, should be interpreted with caution and larger sample study is needed to verify these findings. Second, most of the cases were diagnosed with biopsy samples at advanced clinical stage, which could not allow specific PSC subtypes classification. Third, although we tried to adopt scRNA-seq to map the TME of PSC, the sample size was very limited due to the rarity of the disease and difficult diagnosis in pathology. Finally, longer follow-up was needed to confirm the OS benefits of ICIs in combination with chemotherapy in PSC.

In conclusion, the present, multi-institutional, real-world study demonstrated remarkable efficacy of ICIs in combination with chemotherapy as first-line therapy for patient with locally advanced or metastatic PSC. We have previously initiated a prospective, single-arm study to assess the role of camrelizuamb as second-line therapy after platinum-based chemotherapy in patients with locally advanced or metastatic PSC (ChiCTR2000031478). On the basis of these findings, we have amended the trial protocol to prospectively investigate the efficacy of first-line camrelizuamb plus chemotherapy in patients with locally advanced or metastatic PSC.

Supplemental Material

sj-docx-1-tam-10.1177_17588359221136759 – Supplemental material for Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study

Supplemental material, sj-docx-1-tam-10.1177_17588359221136759 for Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study by Fei Zhou, Haoyue Guo, Xiaolong Zhou, Huikang Xie, Tian Tian, Wencheng Zhao, Guanghui Gao, Anwen Xiong, Lei Wang, Wei Li, Xiaoxia Chen, Yan Zhang, Jue Fan, Fengying Wu, Yongchang Zhang and Caicun Zhou in Therapeutic Advances in Medical Oncology

Supplemental Material

sj-docx-2-tam-10.1177_17588359221136759 – Supplemental material for Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study

Supplemental material, sj-docx-2-tam-10.1177_17588359221136759 for Immune checkpoint inhibitors plus chemotherapy in patients with locally advanced or metastatic pulmonary sarcomatoid carcinoma: a multicentric real-world study by Fei Zhou, Haoyue Guo, Xiaolong Zhou, Huikang Xie, Tian Tian, Wencheng Zhao, Guanghui Gao, Anwen Xiong, Lei Wang, Wei Li, Xiaoxia Chen, Yan Zhang, Jue Fan, Fengying Wu, Yongchang Zhang and Caicun Zhou in Therapeutic Advances in Medical Oncology

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

Fei Zhou

Caicun Zhou

Supplemental material

Supplemental material for this article is available online.

References

Travis

Brambilla

Nicholson

, et al. The 2015 world health organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 2015;10: 1243–1260.

Martin

Correa

Ordonez

, et al. Sarcomatoid carcinoma of the lung: a predictor of poor prognosis. Ann Thorac Surg 2007; 84: 973–980.

Baldovini

Rossi

Ciarrocchi

Approaches to tumor classification in pulmonary sarcomatoid carcinoma. Lung Cancer (Auckl) 2019; 10: 131–149.

Liu

, et al. Pulmonary sarcomatoid carcinoma: progress, treatment and expectations. Ther Adv Med Oncol 2020; 12: 1758835920950207.

Sun

Jiang

Shan

, et al. Characteristics and prognostic analysis of 55 patients with pulmonary sarcomatoid carcinoma. Front Oncol 2022; 12: 833486.

Vieira

Girard

Ung

, et al. Efficacy of first-line chemotherapy in patients with advanced lung sarcomatoid carcinoma. J Thorac Oncol 2013; 8: 1574–1577.

Yang

, et al. Integrated molecular characterization reveals potential therapeutic strategies for pulmonary sarcomatoid carcinoma. Nat Commun 2020; 11: 4878.

Zhou

Huang

Cai

, et al. The genomic and immunologic profiles of pure pulmonary sarcomatoid carcinoma in Chinese patients. Lung Cancer 2021; 153: 66–72.

Schrock

Frampton

, et al. Pulmonary sarcomatoid carcinomas commonly harbor either potentially targetable genomic alterations or high tumor mutational burden as observed by comprehensive genomic profiling. J Thorac Oncol 2017; 12: 932–942.

10.

Domblides

Leroy

Monnet

, et al. Efficacy of immune checkpoint inhibitors in lung sarcomatoid carcinoma. J Thorac Oncol 2020; 15: 860–866.

11.

Lee

Choi

Jung

, et al. Outstanding clinical efficacy of PD-1/PD-L1 inhibitors for pulmonary pleomorphic carcinoma. Eur J Cancer 2020; 132: 150–158.

12.

Gandhi

Rodriguez-Abreu

Gadgeel

, et al. Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer. N Engl J Med 2018; 378: 2078–2092.

13.

Paz-Ares

Luft

Vicente

, et al. Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 2018; 379: 2040–2051.

14.

Zhou

Lin

Zhang

, et al. First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy. J Immunother Cancer 2019; 7: 120.

15.

Dafni

Tsourti

Vervita

, et al. Immune checkpoint inhibitors, alone or in combination with chemotherapy, as first-line treatment for advanced non-small cell lung cancer. a systematic review and network meta-analysis. Lung Cancer 2019; 134: 127–140.

16.

Nicholson

Tsao

Beasley

, et al. The 2021 WHO classification of lung tumors: impact of advances since 2015. J Thorac Oncol 2022; 17: 362–387.

17.

Goldstraw

Chansky

Crowley

, et al. The IASLC lung cancer staging project: proposals for revision of the TNM stage groupings in the forthcoming (Eighth) edition of the TNM classification for lung cancer. J Thorac Oncol 2016; 11: 39–51.

18.

Eisenhauer

Therasse

Bogaerts

, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228–247.

19.

Fan

, et al. Single-cell profiling of tumor heterogeneity and the microenvironment in advanced non-small cell lung cancer. Nat Commun 2021; 12: 2540.

20.

Liu

, et al. Patients with short PFS to EGFR-TKIs predicted better response to subsequent Anti-PD-1/PD-L1 based immunotherapy in EGFR common mutation NSCLC. Front Oncol 2021; 11: 639947.

21.

Babacan

Pina

Signorelli

, et al. Relationship between programmed death receptor-ligand 1 expression and response to checkpoint inhibitor immunotherapy in pulmonary sarcomatoid carcinoma: a pooled analysis. Clin Lung Cancer 2020; 21: e456–e463.

22.

Kim

Keam

Ock

, et al. Phase II study of durvalumab and tremelimumab in pulmonary sarcomatoid carcinoma: KCSG-LU16-07. Thorac Cancer 2020; 11: 3482–3489.

23.

Zhou

Chen

Huang

, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med 2021; 9: 305–314.

24.

Wang

, et al. Tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non-small-cell lung cancer: a phase 3 randomized clinical trial. JAMA Oncol 2021; 7: 709–717.

25.

Mazieres

Drilon

Lusque

, et al. Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Ann Oncol 2019; 30: 1321–1328.

26.

Sabari

Leonardi

Shu

, et al. PD-L1 expression, tumor mutational burden, and response to immunotherapy in patients with MET exon 14 altered lung cancers. Ann Oncol 2018; 29: 2085–2091.

27.

Paik

Felip

Veillon

, et al. Tepotinib in non-small-cell lung cancer with MET Exon 14 skipping mutations. N Engl J Med 2020; 383: 931–943.

28.

Wolf

Seto

Han

, et al. Capmatinib in MET Exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med 2020; 383: 944–957.

29.

Fang

, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small-cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. Lancet Respir Med 2021; 9: 1154–1164.

30.

Hsieh

Lin

Lee

YH.

Lung adenocarcinoma with sarcomatoid transformation after tyrosine kinase inhibitor treatment and chemotherapy. Lung Cancer 2019; 137: 76–84.

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