Neoadjuvant immunochemotherapy in resectable non-small cell lung cancer: the more cycles, the better?
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ABSTRACT:
SUBMITTER: Ulas EB
PROVIDER: S-EPMC10413032 | biostudies-literature | 2023 Jul
REPOSITORIES: biostudies-literature
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Neoadjuvant immunochemotherapy in resectable non-small cell lung cancer: the more cycles, the better?
Translational lung cancer research 20230718 7
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Project description:BackgroundNeoadjuvant immunotherapy, the focus of current research and treatment modality for long-term survival, has become one of the main options in supporting primary treatment interventions in early NSCLC.MethodsThis was a retrospective analysis of patients with locally resectable NSCLC who received the neoadjuvant drug pembrolizumab combined with chemotherapy and underwent surgical resection. Pathological responses, PFS and OS in the whole sample and subgroups were analyzed.ResultsOf the 61 patients included in this retrospective analysis, 31 (50.82%) achieved a pCR, and 38 (62.30%) obtained an MPR. Patients with a pCR had significantly higher OS than the non-pCR group (HR = 0.093, P = 0.0227); patients with an MPR also had significantly elevated OS compared with the non-MPR group (HR = 0.05357, P = 0.0169). Patients with lymph node metastasis after surgery had significantly reduced OS (HR = 0.01607, p = 0.0004) and PFS (HR = 0.08757, p = 0.0004) than those without lymph node metastasis. There was no significant difference in OS and PFS between squamous cell carcinomas (SCC) group and adenocarcinomas (AD) group. No significant differences in OS and PFS were found between patients administered 2 and 3 cycles of neoadjuvant therapy before surgery, between those administered ≤5 and > 5 cycles of adjuvant therapy post-surgery, and between patients with TPS <50% and ≥50% (all P > 0.05).ConclusionNeoadjuvant immunochemotherapy with pembrolizumab plus chemotherapy in non-small cell lung cancer is safe and tolerable. Both pCR and MPR were closely associated with OS and PFS, reflecting a good response of tumor tissues to drug therapy. Lymph node metastasis after surgery was a poor prognostic factor, reducing OS and PFS.
| S-EPMC10559199 | biostudies-literature
Project description:This study evaluated the efficacy of neoadjuvant immunochemotherapy (Io+Chemo) versus chemotherapy alone (Chemo) in resectable non-small cell lung cancer (NSCLC) in a real-world setting. The association of tumor immune microenvironment (TIME) with pathologic response to different neoadjuvant therapies was also explored.Stage I-III NSCLC patients who received Io+Chemo or Chemo alone followed by surgery were included in the study. Tumor tissues collected during surgery were subjected to TIME evaluation using multiplex immunohistochemistry to measure immune cell subsets, including T cells, B cells, NK cells, and macrophages. Fifty-five patients were included, including 24 treated with neoadjuvant Io+Chemo and 31 with Chemo alone. Io+Chemo induced significantly higher major pathologic response (MPR) (75.0% vs. 38.7%, P = 0.0133) and numerically better pathologic complete response (pCR) (33.3% vs. 12.9%, P = 0.1013) than Chemo. Compared with tumors with Chemo, tumors with Io+Chemo demonstrated a significantly higher ratio of M1 macrophage density in the tumor to that in the stroma (P = 0.0446), more abundant CD8+ cells in the stroma (P = 0.0335), and fewer PD-L1+CD68+ cells in both tumor and stroma. pCR/MPR patients displayed significantly higher density of CD3+, CD3+CD4+, CD20+, CD56 bright cell subsets and more tertiary lymphoid structures and significantly lower density of PD-L1+CD68+ and CD3+CD4+Foxp3+cells in the tumor or stroma. This study favored neoadjuvant Io+Chemo over Chemo and revealed the TIME features underlying the outperformance of Io+Chemo over Chemo.
| S-EPMC9582151 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.
| S-EPMC9215714 | biostudies-literature
Project description:The advent of immune checkpoint inhibition has pushed the treatment paradigm for resectable non-small-cell lung cancer (NSCLC) toward neoadjuvant therapy. A growing number of promising trials have examined the utility of neoadjuvant immunotherapy, both alone and in combination with other modalities such as radiation therapy (RT) and chemotherapy. The phase II LCMC3 and NEOSTAR trials demonstrated a role for neoadjuvant immunotherapy in inducing meaningful pathologic responses, and another phase II trial established the feasibility of combining neoadjuvant durvalumab with RT. Significant interest in neoadjuvant chemoimmunotherapy resulted in the conduct of multiple successful phase II trials including the Columbia trial, NADIM, SAKK 16/14, and NADIM II. Across these trials, neoadjuvant chemoimmunotherapy led to high rates of pathologic response and improved surgical outcomes without compromising surgical timing or feasibility. CheckMate-816, which was a randomized phase III trial studying neoadjuvant nivolumab in addition to chemotherapy, definitively established a benefit for neoadjuvant chemoimmunotherapy compared to chemotherapy alone for resectable NSCLC. Despite the growing literature and success of these trials, several outstanding questions remain, including the relationship between pathologic response and patient survival, the role of biomarkers such as programmed death ligand 1 and circulating tumor DNA in determining patient selection and treatment course, and the utility of additional adjuvant therapies. Longer follow-up of CheckMate-816 and other ongoing phase III trials may help address these questions. Ultimately, the complexity of managing resectable NSCLC highlights the importance of a multidisciplinary approach to patient care.
| S-EPMC10052589 | biostudies-literature
Project description:Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. In recent ten years, with the emergence of new drugs and the optimization of treatment mode, the treatment of lung cancer is entering an era of precision and individualization. Neoadjuvant therapy can reduce tumor size, degrade tumor stage, kill circulating tumor cells and micrometastases in the body, afford operation possibility, and benefit the long-term survival of patients. However, the traditional neoadjuvant chemotherapy combined with surgical treatment seems to have entered the bottleneck period of efficacy and is difficult to achieve breakthrough progress. At the same time, the amazing efficacy of immunotherapy is gradually innovating the treatment mode of lung cancer. In recent years, the research data of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) shows an explosive growth. Immunotherapy has been applied to the first-line treatment of advanced NSCLC. Therefore, some clinical trials have applied immunotherapy to neoadjuvant treatment of resectable NSCLC patients. In this paper, the efficacy, possible mechanisms, potential risks and existing problems of neoadjuvant immunotherapy for resectable NSCLC patients are reviewed, and the future development direction of neoadjuvant immunotherapy is discussed.
| S-EPMC8263648 | biostudies-literature
Project description: Not available
| S-EPMC10083171 | biostudies-literature
Project description:We conducted the first trial of neoadjuvant PD-1 blockade in resectable non-small cell lung cancer (NSCLC), finding nivolumab monotherapy to be safe and feasible with an encouraging rate of pathologic response. Building on these results, and promising data for nivolumab plus ipilimumab (anti-CTLA-4) in advanced NSCLC, we expanded our study to include an arm investigating neoadjuvant nivolumab plus ipilimumab. Patients with resectable stage IB (≥4 cm)-IIIA (American Joint Committee on Cancer Tumor Node Metastases seventh edition), histologically confirmed, treatment-naïve NSCLC received nivolumab 3 mg/kg intravenously plus ipilimumab 1 mg/kg intravenously 6 weeks prior to planned resection. Nivolumab 3 mg/kg was given again approximately 4 and 2 weeks preoperatively. Primary endpoints were safety and feasibility with a planned enrollment of 15 patients. Pathologic response was a key secondary endpoint. While the treatment regimen was feasible per protocol, due to toxicity, the study arm was terminated early by investigator consensus after 9 of 15 patients were enrolled. All patients received every scheduled dose of therapy and were fit for planned surgery; however, 6 of 9 (67%) experienced treatment-related adverse events (TRAEs) and 3 (33%) experienced grade ≥3 TRAEs. Three of 9 patients (33%) had biopsy-confirmed tumor progression precluding definitive surgery. Of the 6 patients who underwent resection, 3 are alive and disease-free, 2 experienced recurrence and are actively receiving systemic treatment, and one died postoperatively due to acute respiratory distress syndrome. Two patients who underwent resection had tumor pathologic complete responses (pCRs) and continue to remain disease-free over 24 months since surgery. Pathologic response correlated with pre-treatment tumor PD-L1 expression, but not tumor mutation burden. Tumor KRAS/STK11 co-mutations were identified in 5 of 9 patients (59%), of whom two with disease progression precluding surgery had tumor KRAS/STK11/KEAP1 co-mutations. Though treatment was feasible, due to toxicity the study arm was terminated early by investigator consensus. In light of this, and while the long-term disease-free status of patients who achieved pCR is encouraging, further investigation of neoadjuvant nivolumab plus ipilimumab in patients with resectable NSCLC requires the identification of predictive biomarkers that enrich for response.
| S-EPMC7488786 | biostudies-literature
Project description:Resectable non-small cell lung cancer (NSCLC) is currently considered as a potentially curable disease. Surgery is still the main treatment mode for resectable NSCLC, but quite a few patients will have local recurrence and distant metastasis after surgery. Therefore, preoperative and postoperative adjuvant therapy may be necessary in order to improve the long term outcome. Immunocheckpoint inhibitor has been demonstrated clinically to be effective andapproved as first- or second-line treatment agent in metastatic NSCLC or partially locally advanced NSCLC. The remarkable efficacy of immunotherapy for advanced lung cancer has attracted more and more attention from the researchers to the role of immunotherapy as neoadjuvent therapy in resectable non-small cell lung cancer. This article systematically reviewed the clinical trials of neoadjuvant immunotherapy for resectable NSCLC before surgery.
| S-EPMC7260379 | biostudies-literature
Project description:BackgroundNo consensus exists regarding the optimal number of cycles of neoadjuvant immunochemotherapy for patients with stage IB-IIIB non-small cell lung cancer (NSCLC). In this study, we compared the efficacy and safety of 2 cycles of neoadjuvant immunochemotherapy in stage IB-IIIB NSCLC with those of 3-4 cycles.MethodsAll patients with IB-IIIB NSCLC who received preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, from 2019 to 2022 were consecutively included in this retrospective study. Subsequently, 1:1 propensity score matching (PSM) according to baseline characteristics was performed to compare the efficacy and safety between the 2-cycle group and the 3 to 4-cycle group. The follow-up period was required to be at least 1 year after surgery or when the patient decided to abandon treatment.ResultsOf the 184 patients with stage IB-IIIB NSCLC included in the analysis, 61 received 2 cycles of neoadjuvant immunochemotherapy while 123 received 3-4 cycles. After a 1:1 PSM, there were no significant differences in baseline clinicopathological characteristics among the108 patients (54 pairs) who received 2 cycles or 3-4 cycles of neoadjuvant immunochemotherapy. The objective response rate (ORR) in the 3 to 4-cycle group was significantly higher than that in the 2-cycle group (83.3% vs. 63.0%; P=0.01). The incidence of grade 3-4 adverse events (AEs) in the 3 to 4-cycle group was similar to that of the 2-cycle group (13.0% vs. 9.3%; P=0.54). About 90.7% (49/54) of patients in the 2-cycle group and 46.3% (25/54) in the 3 to 4-cycle group eventually underwent surgery. The rate of major pathological response (MPR) in the 3 to 4-cycle group and 2-cycle group was 68.0% and 69.4% (P=0.90), respectively. The rate of pathological complete response (pCR) in the 3 to 4-cycle group and 2-cycle group was 36.0% and 38.8% (P=0.82), respectively. The median disease-free survival (DFS) in the 3 to 4-cycle group and 2-cycle group was not reached (P=0.80). The 1-year DFS rate and 2-year DFS rate in the 2-cycle group were 87.8% and 77.6%, respectively, while those in the 3 to 4-cycle group were 80.0% and 76.0%, respectively. The median overall survival (OS) in the 2-cycle group was 42.4 months, and it was not reached in the 3 to 4-cycle group (P=0.42). The 1-year OS rate and 2-year OS rate in the 2-cycle group were 93.9% and 87.8%, respectively, while those in the 3 to 4-cycle group were 88.0% and 80.0%, respectively.ConclusionsThree to four cycles of neoadjuvant immunochemotherapy can result in more tumor regression in IB-IIIB NSCLC. Extending the number of cycles to 3-4 cycles may be feasible and safe in IB-IIIB NSCLC.
| S-EPMC11898355 | biostudies-literature
Project description:Lung cancer is one of the most common malignant tumors and it is the leading cause of cancer-related mortality worldwide. For early-stage Non-Small Cell Lung Cancer (NSCLC), surgical resection is the treatment of choice, but the 5-year survival is still unsatisfying, ranging from 60% to 36% depending on the disease stage. Multimodality treatment with adjuvant chemotherapy did not lead to clinically relevant results, improving survival rates by only 5%. Recently, immune checkpoint inhibitors (ICIs) are being studied as neoadjuvant treatment for resectable NSCLC too, after the satisfactory results obtained in stage IV disease. Several clinical trials are evaluating the safety and feasibility of neoadjuvant immunotherapy and their early findings suggest that ICIs could be better tolerated than standard neoadjuvant chemotherapy and more effective in reducing cancer local recurrence and metastasis. The aim of this review is to retrace the most relevant results of the completed and the ongoing clinical trials, in terms of efficacy and safety, but also to face the open challenges regarding ICIs in neoadjuvant setting for resectable NSCLC.
| S-EPMC8539920 | biostudies-literature