Immune Checkpoint Inhibitors in Lung Cancer: Role of Biomarkers and Combination Therapies

Maung, Tun Zan; Ergin, Huseyin Ekin; Javed, Mehwish; Inga, E.; Khan, Safeera

doi:10.7759/cureus.8095

Cited by 21 publications

(21 citation statements)

References 41 publications

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“…Besides PD-L1 expression, TMB, DNA mismatch repair deficiency, extent of CD8+ cell infiltration, immune gene expression signatures and composition of the gut microbiome have also been proposed to correlate with clinical response to anti-PD-1/PD-L1 ICIs (29)(30)(31)(32). NSCLC patients with high TMB and the smokers were found to respond better to anti-PD-1/PD-L1 ICIs (33).…”

Section: Predictive Biomarkers For Selecting Nsclc Patients For Immunotherapymentioning

confidence: 99%

Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies

Fong

Cho

2021

Front. Oncol.

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Lung cancer is the leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors, including monoclonal antibodies against programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have dramatically improved the survival and quality of life of a subset of non-small cell lung cancer (NSCLC) patients. Multiple predictive biomarkers have been proposed to select the patients who may benefit from the immune checkpoint inhibitors. EGFR-mutant NSCLC is the most prevalent molecular subtype in Asian lung cancer patients. However, patients with EGFR-mutant NSCLC show poor response to anti-PD-1/PD-L1 treatment. While small-molecule EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for EGFR-mutant NSCLC, acquired drug resistance is severely limiting the long-term efficacy. However, there is currently no further effective treatment option for TKIs-refractory EGFR-mutant NSCLC patients. The reasons mediating the poor response of EGFR-mutated NSCLC patients to immunotherapy are not clear. Initial investigations revealed that EGFR-mutated NSCLC has lower PD-L1 expression and a low tumor mutational burden, thus leading to weak immunogenicity. Moreover, the use of PD-1/PD-L1 blockade prior to or concurrent with osimertinib has been reported to increase the risk of pulmonary toxicity. Furthermore, emerging evidence shows that PD-1/PD-L1 blockade in NSCLC patients can lead to hyperprogressive disease associated with dismal prognosis. However, it is difficult to predict the treatment toxicity. New biomarkers are urgently needed to predict response and toxicity associated with the use of PD-1/PD-L1 immunotherapy in EGFR-mutated NSCLC. Recently, promising data have emerged to suggest the potentiation of PD-1/PD-L1 blockade therapy by anti-angiogenic agents and a few other novel therapeutic agents. This article reviews the current investigations about the poor response of EGFR-mutated NSCLC to anti-PD-1/PD-L1 therapy, and discusses the new strategies that may be adopted in the future.

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Section: Predictive Biomarkers For Selecting Nsclc Patients For Immunotherapymentioning

confidence: 99%

Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies

Fong

Cho

2021

Front. Oncol.

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“…Surgery combined with preoperative adjuvant therapy has been the mainstay of treatment for patients with advanced stage NSCLC, 4 but complete resection is affected by the size and location of the tumor. There is a critical need to develop better therapeutic approaches to treat patients with locally advanced stage disease 5 . Increasing numbers of guidelines recommend targeted or adjuvant immunotherapy for patients with locally advanced NSCLC in order to maximize benefit to patients 6 …”

Section: Introductionmentioning

confidence: 99%

Surgical perspective in neoadjuvant chemoimmunotherapy for stage II–III non‐small cell lung cancer

et al. 2021

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Background There are many studies on neoadjuvant immunotherapy for locally advanced non‐small cell lung cancer (NSCLC) patients. Expert consensus recommends neoadjuvant immunotherapy for patients with resectable stage IB–IIIA NSCLC. However, there are few clinical studies or cases to verify this. Methods Data were collected from all NSCLC patients who underwent surgical resection after neoadjuvant chemoimmunotherapy admitted to the Affiliated Hospital of Xuzhou Medical University and Xuzhou Central Hospital between September 2020 and April 2021. Data collected included patient information, relevant examination results, intraoperative parameters, postoperative complications, pathological changes, and 90‐day mortality. Results In total, 25 patients achieved R0 resection. Eleven (44%) patients completed surgery by thoracotomy, and three (12%) procedures were changed from minimally invasive procedures due to dense adhesions of hilar lymph nodes, which rendered it difficult to dissect the blood vessels. Thirteen (52%) patients achieved a major pathological response (MPR) with eight (32%) of these patients having a pathological complete response (pCR). Twenty‐two (88%) patients showed radiological regression, and three (12%) patients had stable disease. The median drainage time was 8.50 (3–27) days. Thirteen (52%) postoperative complications were observed, but none were above grade 3. Conclusions In this study, neoadjuvant chemoimmunotherapy was found to reduce tumor volume, cause pathological downstaging, and raise the surgical resection rate of patients with locally advanced NSCLC, and achieve a 100% R0 resection rate. There was an acceptable rate of postoperative complications. Thus, neoadjuvant chemoimmunotherapy is safe and practical.

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“…As few studies have analysed the efficiency and safety of ICI treatment in patients with SCLC, and no comparison directly included patients with SCLC versus those with NSCLC, to a certain extent, we bridged the gap in efficiency and safety data for ICI therapy among patients with NSCLC and SCLC. Previously, Maung et al have shown that ICIs conferred better survival benefits than chemotherapy in both NSCLC and SCLC [ 53 ]. However, their conclusions were mainly based on qualitative analysis, without data analysis of clinical trials.…”

Section: Discussionmentioning

confidence: 99%

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer

Wang

Zhang

et al. 2021

BMC Cancer

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Background The advent of immune checkpoint inhibitors (ICIs) therapy has resulted in significant survival benefits in patients with non-small-cell lung cancer (NSCLC) without increasing toxicity. However, the utilisation of immunotherapy for small-cell lung cancer (SCLC) remains unclear, with a scarcity of systematic comparisons of therapeutic effects and safety of immunotherapy in these two major lung cancer subtypes. Herein, we aimed to provide a comprehensive landscape of immunotherapy and systematically review its specific efficacy and safety in advanced lung cancer, accounting for histological types. Methods We identified studies assessing immunotherapy for lung cancer with predefined endpoints, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and treatment-related adverse events (TRAE), from PubMed, Embase, Medline, and Cochrane library. A random-effects or fixed-effect model was adopted according to different settings. Results Overall, 38 trials with 20,173 patients with lung cancer were included in this study. ICI therapy resulted in a significantly prolonged survival in both patients with NSCLC and SCLC when compared with chemotherapy (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.70–0.79] and [HR = 0.82; 95% CI, 0.75–0.90], respectively). The magnitude of disease control and survival benefits appeared superior with ICI plus standard of care (SOC) when compared with SOC alone. OS and PFS advantages were observed only when immunotherapy was employed as the first-line treatment in patients with SCLC. Conclusion ICI therapy is a promising therapeutic option in patients with NSCLC and SCLC. ICI plus SOC can be recommended as the optimal first-line treatment for patients with SCLC, and double-target ICIs combined with SOC are recommended in patients with NSCLC as both the first and subsequent lines of treatment. Additionally, non-first-line immunotherapy is not recommended in patients with SCLC.

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Immune Checkpoint Inhibitors in Lung Cancer: Role of Biomarkers and Combination Therapies

Cited by 21 publications

References 41 publications

Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies

Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies

Surgical perspective in neoadjuvant chemoimmunotherapy for stage II–III non‐small cell lung cancer

The landscape of immune checkpoint inhibitor therapy in advanced lung cancer

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