Dataset Information

Pathologic response and safety to neoadjuvant PD-1 inhibitors and chemotherapy in resectable squamous non-small-cell Lung cancer.

ABSTRACT:

Background

Several randomized studies have shown that the combination of programmed cell death 1 (PD-1) inhibitor and chemotherapy is efficacious as a treatment for advanced non-small-cell lung cancer (NSCLC). However, in the neoadjuvant setting, there is scarce evidence of the effectiveness and safety of the combinations in squamous NSCLC. We conducted a retrospective study to evaluate neoadjuvant PD-1 inhibitor plus chemotherapy in resectable squamous NSCLC.

Methods

Patients from Beijing Chest Hospital, Capital Medical University, between October 2019 and October 2021, treated with PD-1 inhibitors and chemotherapy for resectable squamous NSCLC were retrospectively studied. The primary objectives were to assess the pathological tumor response and safety of neoadjuvant PD-1 inhibitors and chemotherapy.

Results

63 patients with resectable squamous NSCLC stage IIA-IIIB were included. Two to four cycles of PD-1 inhibitors (37 cases with camrelizumab, 11 cases with toripalimab, 8 cases with tislelizumab, and 7 cases with sintilimab) and chemotherapy were administered prior to surgery. 42 patients (66.7%) achieved a major pathologic response (MPR), including 25 (39.7%) with a pathologic complete response (pCR). Twenty-one patients (33.3%) experienced grade 3 neoadjuvant treatment-related adverse events (TRAEs), and no patient had grade 4 or 5 TRAE.

Conclusion

Neoadjuvant PD-1 inhibitors and chemotherapy are feasible therapies for resectable squamous NSCLC. It was associated with a 66.7% MPR rate, 39.7% pCR rate, and tolerable toxicity.

SUBMITTER: Shi L

PROVIDER: S-EPMC9614263 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Pathologic response and safety to neoadjuvant PD-1 inhibitors and chemotherapy in resectable squamous non-small-cell Lung cancer.

Shi Liang L Meng Qiyi Q Tong Li L Li Hongxia H Dong Yujie Y Su Chongyu C Liu Zhe Z

Frontiers in oncology 20221014

<h4>Background</h4>Several randomized studies have shown that the combination of programmed cell death 1 (PD-1) inhibitor and chemotherapy is efficacious as a treatment for advanced non-small-cell lung cancer (NSCLC). However, in the neoadjuvant setting, there is scarce evidence of the effectiveness and safety of the combinations in squamous NSCLC. We conducted a retrospective study to evaluate neoadjuvant PD-1 inhibitor plus chemotherapy in resectable squamous NSCLC.<h4>Methods</h4>Patients fro ...[more]

PMID: 36313678

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Project description:BackgroundA single-agent of anti programmed cell death 1/programmed cell death ligand 1 (anti-PD-1/PD-L1) therapy has been explored for resectable lung cancer before surgery. However, the effectiveness and safety of neoadjuvant programmed cell death 1 (PD-1) blockade combined with chemotherapy have not been published.MethodsTwenty-one consecutive patients with potentially resectable squamous cell carcinoma of the lung who received neoadjuvant therapy followed by surgery in Beijing Cancer Hospital were included in this study. Eight patients received two cycles of neoadjuvant platinum-based doublet chemotherapy combined with anti-programmed cell death 1 (anti-PD-1) therapy, while 13 patients received two cycles of neoadjuvant platinum-based doublet chemotherapy only. Chest computed tomography was repeated before neoadjuvant treatment and surgery. Adverse events were monitored. The major pathological response (MPR) rate was determined after surgery. Selected specimens were sent for immunohistochemical and multiplex immunofluorescence analyses, and T-cell receptor DNA sequencing.ResultsCompared with neoadjuvant chemotherapy alone, the combination of PD-1 blockade and chemotherapy increased the pathological complete response rate (37.5% vs. 7.69%) and MPR rate (50% vs. 38.46%). The pathological and radiological evaluations are not consistent. No unknown adverse effects were reported for all the patients. More tumor infiltrating lymphocytes were observed in patients who received PD-1 blockade. No unknown pathological features associated with PD-1 blockade were found. Immune suppression in the peritumoral spaces around the residual tumor cells was observed. The amino acid sequences of the T-cell receptors are not significantly shared among the patients.ConclusionsThe combination of neoadjuvant chemotherapy and PD-1 blockade is safe and feasible, and might indicate an increased MPR and pathological complete response rate. More investigations are needed for the best combination of the neoadjuvant therapy.

Project description:BackgroundAntibodies that block programmed death 1 (PD-1) protein improve survival in patients with advanced non-small-cell lung cancer (NSCLC) but have not been tested in resectable NSCLC, a condition in which little progress has been made during the past decade.MethodsIn this pilot study, we administered two preoperative doses of PD-1 inhibitor nivolumab in adults with untreated, surgically resectable early (stage I, II, or IIIA) NSCLC. Nivolumab (at a dose of 3 mg per kilogram of body weight) was administered intravenously every 2 weeks, with surgery planned approximately 4 weeks after the first dose. The primary end points of the study were safety and feasibility. We also evaluated the tumor pathological response, expression of programmed death ligand 1 (PD-L1), mutational burden, and mutation-associated, neoantigen-specific T-cell responses.ResultsNeoadjuvant nivolumab had an acceptable side-effect profile and was not associated with delays in surgery. Of the 21 tumors that were removed, 20 were completely resected. A major pathological response occurred in 9 of 20 resected tumors (45%). Responses occurred in both PD-L1-positive and PD-L1-negative tumors. There was a significant correlation between the pathological response and the pretreatment tumor mutational burden. The number of T-cell clones that were found in both the tumor and peripheral blood increased systemically after PD-1 blockade in eight of nine patients who were evaluated. Mutation-associated, neoantigen-specific T-cell clones from a primary tumor with a complete response on pathological assessment rapidly expanded in peripheral blood at 2 to 4 weeks after treatment; some of these clones were not detected before the administration of nivolumab.ConclusionsNeoadjuvant nivolumab was associated with few side effects, did not delay surgery, and induced a major pathological response in 45% of resected tumors. The tumor mutational burden was predictive of the pathological response to PD-1 blockade. Treatment induced expansion of mutation-associated, neoantigen-specific T-cell clones in peripheral blood. (Funded by Cancer Research Institute-Stand Up 2 Cancer and others; ClinicalTrials.gov number, NCT02259621 .).

Project description:BackgroundNeoadjuvant or adjuvant chemotherapy confers a modest benefit over surgery alone for resectable non-small-cell lung cancer (NSCLC). In early-phase trials, nivolumab-based neoadjuvant regimens have shown promising clinical activity; however, data from phase 3 trials are needed to confirm these findings.MethodsIn this open-label, phase 3 trial, we randomly assigned patients with stage IB to IIIA resectable NSCLC to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection. The primary end points were event-free survival and pathological complete response (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. Overall survival was a key secondary end point. Safety was assessed in all treated patients.ResultsThe median event-free survival was 31.6 months (95% confidence interval [CI], 30.2 to not reached) with nivolumab plus chemotherapy and 20.8 months (95% CI, 14.0 to 26.7) with chemotherapy alone (hazard ratio for disease progression, disease recurrence, or death, 0.63; 97.38% CI, 0.43 to 0.91; P = 0.005). The percentage of patients with a pathological complete response was 24.0% (95% CI, 18.0 to 31.0) and 2.2% (95% CI, 0.6 to 5.6), respectively (odds ratio, 13.94; 99% CI, 3.49 to 55.75; P<0.001). Results for event-free survival and pathological complete response across most subgroups favored nivolumab plus chemotherapy over chemotherapy alone. At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI, 0.30 to 1.07) and did not meet the criterion for significance. Of the patients who underwent randomization, 83.2% of those in the nivolumab-plus-chemotherapy group and 75.4% of those in the chemotherapy-alone group underwent surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group.ConclusionsIn patients with resectable NSCLC, neoadjuvant nivolumab plus chemotherapy resulted in significantly longer event-free survival and a higher percentage of patients with a pathological complete response than chemotherapy alone. The addition of nivolumab to neoadjuvant chemotherapy did not increase the incidence of adverse events or impede the feasibility of surgery. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

Project description:BackgroundEsophageal squamous cell cancer (ESCC) patients with the potentially resectable disease most would experience relapse after surgery. Immunotherapy has been reported to improve the prognosis of advanced esophageal cancer and may be a new strategy to prevent this urgent condition's recurrence. We first evaluated the efficacy and safety of neoadjuvant chemotherapy combined with immunotherapy in patients with resectable ESCC.MethodsAll patients with resectable locally advanced ESCC (clinical stage III-IVB). Received at least 1 cycle of neoadjuvant chemotherapy combined with immunotherapy (NACI), and the interval between each cycle and the operation should be at least 3 weeks. All patients were treated with standard surgery. The tumor imaginations were obtained at baseline and within a week before surgery. The efficacy endpoint was the rate of major pathologic response (MPR, 10% viable tumor cells). Expression of immunohistochemical-related molecules was investigated in surgical samples.ResultsA total of 38 patients with ESCC were included (36 males, median age 61 years), and most of them used Pembrolizumab (55.26%) and Camrelizumab (31.58%). We analyzed 19 patients and found that 13 patients (68.42%) achieved radiological partial response (PR) by CT images. R0 resection was performed in 35 patients (92.11%), and 10 patients (26.32%) developed postoperative complications. Through postoperative pathology, we found 13 (34.21%) patients had complete pathologic response (cPR), and 16 (42.11%) patients achieved MPR. We also found that none of the factors had a statistically significant impact on MPR. Still, the regression rate of Sum of lesion diameter (SLD) was significantly positively correlated with the pathological remission rate (P=0.012, r=0.565).ConclusionsThe rate of MPR in ESCC patients reached 42.11%. The use of the NACI regimen did not increase the occurrence of complications in neoadjuvant treatment and operation, and the SLD regression rate has a certain guiding significance for the effect of immunotherapy.

Dataset Information

Pathologic response and safety to neoadjuvant PD-1 inhibitors and chemotherapy in resectable squamous non-small-cell Lung cancer.

Background

Methods

Results

Conclusion

Publications

Pathologic response and safety to neoadjuvant PD-1 inhibitors and chemotherapy in resectable squamous non-small-cell Lung cancer.

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