Real World Radiographic Response Rates and Preoperative Attrition in Patients With Non-Small Cell Lung Cancer (NSCLC) Treated With Neoadjuvant Chemoimmunotherapy.

Chemotherapy + PD-1/PD-L1 Blockade Should Be the Preferred Option in the Neoadjuvant Therapy of NSCLC

Tertiary lymphoid structures (TLS) existence is correlated with favorable prognosis in many types of cancer including non-small cell lung cancer (NSCLC). However, TLS formation and its relationship with treatment response...

While some clinical studies have shown that PD-1 and PD-L1 can also be an effective neoadjuvant treatment for early-stage non-small cell lung cancer (NSCLC), no evidence has been available for the use of the PD-1 inhibitor sintilimab combined with chemotherapy as a neoadjuvant treatment for potentially resectable NSCLC in the Chinese population. This prospective, single-center, single-arm, phase 2 clinical trial (registration number: NCT04326153) included treatment-naive patients with potentially resectable NSCLC (stage IIIA/IIIB) who received sintilimab plus nab-paclitaxel and carboplatin for two to three cycles before systematic nodal dissection 30 to 45days after neoadjuvant treatment. After surgery, patients needed to complete two cycles of adjuvant chemoimmunotherapy (sintilimab + nab-paclitaxel + carboplatin). The primary endpoint was disease-free survival rate at 24months, whereas secondary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, the proportion of patients who achieved tumor downstaging, overall survival, objective response rate (ORR), and adverse effects. PD-L1 status before and after treatment was also determined. Among the 20 patients who received neoadjuvant chemoimmunotherapy, 16 underwent radical resection. The disease control rate and ORR were 90% and 70%, respectively. Among the 16 patients who underwent surgery, 10 (62.5%) and 5 (31.25%) achieved MPR and pCR, respectively. Squamous cell NSCLC exhibited superior response rates compared to adenocarcinoma (pCR 35.7% vs. 0%). Moreover, 14 patients (70%) experienced grade 1 or 2 neoadjuvant treatment-related adverse events (TRAEs), whereas 6 (30%) experienced grade 3 TRAEs. Bronchopleural fistula (BPF) was found in the current study as an adverse reaction of concern. The rate of BPF was 20% (4/20), of which three patients were in grade 1-2, and one patient died. The occurrence of BPF had no significant correlation with basic disease history, nutritional status, anemia, hypoalbuminemia, surgical procedure, pathological remission, and PD-L1 expression. However, during neoadjuvant treatment, no adverse events prompted dose reduction, treatment discontinuation, surgery delay, or death. Although PD-L1 expression may change after chemoimmunotherapy, no regular pattern was noted. PD-L1 expression, neither at baseline nor after neoadjuvant chemoimmunotherapy, was associated with pathological remission. The current study found similar ORR, slightly lower MPR and pCR rates, and lower grade 3 TRAEs among patients with potentially resectable stage IIIA/IIIB NSCLC compared to the NADIM trial, as well as a greater ORR, MPR rate, pCR rate, and grade 3 TRAEs compared to Gao's study involving sintilimab for Chinese patients with resectable stage IA-IIIB NSCLC. Though neoadjuvant chemoimmunotherapy had been found to promote a high risk of BPF for patients with stage IIIA/IIIB disease, it offered greater potential for radical cure. Therefore, the current study suggests that neoadjuvant chemoimmunotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.

Surgery and postoperative adjuvant therapy is the standard treatment for locally advanced resectable oral squamous cell carcinoma (OSCC), while neoadjuvant chemoimmunotherapy (NACI) is believed to lead to better outcomes. This study aims to investigate the effectiveness of NACI regimens in treating locally advanced resectable OSCC. Patients diagnosed with locally advanced resectable OSCC who received NACI and non-NACI were reviewed between December 2020 and June 2022 in our single center. The pathologic response was evaluated to the efficacy of NACI treatment. Adverse events apparently related to NACI treatment were graded by Common Terminology Criteria for Adverse Events, version 5.0. The disease-free survival (DFS) and overall survival (OS) rate were assessed. Our analysis involved 104 patients who received NACI. Notably, the pathological complete response rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. The top three grade 1-2 treatment-related adverse events (TRAEs) were alopecia (104; 100%), anemia (81; 77.9%), and pruritus (62; 59.6%). Importantly, patients achieving MPR exhibited higher programmed cell death-ligand 1 (PD-L1) combined positive scores (CPS). The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined with total cholesterol level. The 3-year estimated DFS rates were 89.0% in the NACI cohort compared to 60.8% in the non-NACI cohort, while the 3-year estimated OS rates were 91.3 versus 64.0%, respectively. The NACI treatment showed safe and encouragingly efficacious for locally advanced resectable OSCC patients. The high response rates and favorable prognosis suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings.

The number of cycles of neoadjuvant therapy programmed cell death 1 (PD-1) inhibitor for locally advanced non-small cell lung cancer (NSCLC) remains controversial. From October 2019 to March 2022, neoadjuvant chemoimmunotherapy followed by radical surgery for NSCLC patients with stage II-III were retrospectively reviewed in Shanghai Pulmonary Hospital. The radiologic response was assessed according to the Response Evaluation Criteria for Solid Tumors version 1.1. The major pathological response was defined as no more than 10% residual tumor. Student'st-test, chi-square test, and Mann-Whitney test were used for univariate analysis, logistic regression analysis was used for multivariate analysis. All statistical analyses were calculated by SPSS software (version 26). Among 108 patients, the number of patients who received 2-cycle (2-cycle group) and more than 2-cycle (>2-cycle group) neoadjuvant chemoimmunotherapy were 75 (69.4%) and 33 (30.6%), respectively. Compared with patients inthe >2-cycle group, patients in the 2-cycle group had significantly smaller diagnostic radiological tumor size (37.0mm vs. 49.6mm, p=0.022) and radiological tumor regression rate (36%vs. 49%, p=0.007). However, no significant difference in pathological tumor regression rate was observed between patients in the 2-cycle group and>2-cycle group. Further logistic regression analysis demonstrated that the neoadjuvant chemoimmunotherapy cycle could independently affect the radiographic response (odds ratio [OR]: 0.173, 95% confidence interval [CI]: 0.051-0.584, p=0.005) but not for pathological response (OR: 0.450, 95% CI: 0.161-1.257, p=0.127). For patients diagnosed with stage II-III NSCLC, the number of neoadjuvant cycles administered can significantly influence the radiographic efficacy of chemoimmunotherapy.

背景与目的初步研究证实新辅助免疫联合化疗对可手术非小细胞肺癌近期疗效显著，但国内相关临床试验较少。本研究回顾性分析应用新辅助免疫治疗联合化疗的可手术Ib期-IIIb期非小细胞肺癌的临床病理资料，初步评估新辅助免疫治疗联合化疗的疗效及安全性。方法回顾性分析2019年11月-2020年12月期间于首都医科大学附属北京胸科医院胸外科治疗的临床分期Ib期-IIIb期的非小细胞肺癌患者20例，术前应用免疫联合化疗新辅助治疗，根据影像学和病理学方法分别评估疗效。结果全组患者新辅助治疗后影像学评估疗效，客观有效率（objective response rate, ORR）为85.0%（完全缓解4例，部分缓解13例），疾病稳定1例（5.0%），疾病进展2例（10.0%）。其中17例后续接受手术治疗，16例达到R0（no residual tumor）切除，1例R1（microscopic residual tumor）切除。术后病理评估：主要病理缓解率（major pathologic response, MPR）为47.1%（8/17），其中完全病理缓解率（complete pathologic response, CPR）为29.4%（5/17）。主要不良反应：免疫相关性肺炎（Ⅳ级）1例，Ⅲ级及以上血液学毒性9例（45.0%）。结论新辅助免疫联合化疗对于可手术的非小细胞肺癌近期疗效显著，具有一定的安全性及有效性。但新辅助免疫联合化疗的远期疗效、最佳周期数以及理想预测免疫治疗效果的标记物仍有待研究。

Treatment of locally advanced unresectable non-small cell lung cancer (NSCLC) is a significant challenge, especially for patients with IIIA/IIIB NSCLC. Patients receiving neoadjuvant chemoimmunotherapy (NCI) show improved pathological responses and disease-free survival (DFS) compared to those receiving Neoadjuvant chemotherapy (NC). However, there is still no consensus on the treatment for potentially resectable stage IIIA/IIIB NSCLC. This retrospective study included 71 patients newly diagnosed with stage III NSCLC at our institution between 2017 and 2023: 46 patients received NCI and 25 patients received NC followed by surgical resection. Their clinicopathological characteristics were reviewed and analyzed. Patients who received NCI had a significantly longer DFS. The median DFS was 15 months in the NC group (hazard ratio: 0.186, 95% confidence interval[CI]: 0.073-0.479; P<0.001) but had not been reached in the NCI group. The percentage of patients achieving a major pathologic response was 65.9% (29/44, 95% CI: 50.0%-79.1%) with NCI and 16.7% (4/24, 95% CI: 5.5%-38.2%) with NC alone(P<0.001). The percentage of patients with pathologic complete response was 36.4% (16/44, 95% CI: 22.8%-52.3%) after NCI compared with 8.3% (2/24, 95% CI: 1.5%-28.5%) after NC (P = 0.012). The survival curve shows that the overall survival for the NCI group has a better trend than that of the NC group, but there is no significant difference (P=0.193). The incidence of all-grade adverse events was greater in the NCI group than in the NC group (80.4% vs. 64.0%). The incidence of grade ≥3 adverse events was 10.9% (n=5) and 8.0% (n=2), respectively; however, these differences were insignificant. NCI is more effective and safer for patients with potentially resectable stage IIIA/IIIB NSCLC. Compared with NC alone, NCI significantly improves the pathological response and DFS without increasing adverse events.

In patients with non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy (NCIT), inconsistent pathological responses between the tumor and lymph nodes (LNs) are often observed. There has been limited evidence comparing the different responses of tumors and LNs in those patients. This retrospective real-world analysis intended to evaluate the clinical and pathological response of primary tumors and LNs, and the long-term outcomes in NSCLC patients after NCIT. We included resectable NSCLC patients who had received neoadjuvant therapy and had available clinicopathological records. The progression-free survival (PFS) and overall survival (OS) outcomes were analyzed using survival analysis. In total, 204 patients were included in the final analysis. Patients were predominantly male (85.8%) and ever-smokers (66.2%), with a median age of 63 years. No significant difference was observed in intraoperative bleeding (P=0.51 and P=0.54) and operation time (P=0.57 and P=0.58) between the major pathologic response (MPR) and pathological complete response (pCR) group, respectively. Patients who were male (pCR, P=0.01; MPR, P=0.004), with squamous cell carcinoma (SCC) (pCR, P=0.02; MPR, P=0.001), and overall response rate (ORR) (pCR, P<0.001; MPR, P<0.001) demonstrated significantly higher rates of pCR and MPR. The median follow-up time for all patients in this study was 23 months. Patients with MPR (P=0.004) and pCR (P=0.02) experienced prolonged PFS, but not OS (MPR, P=0.08; pCR, P=0.15). In terms of yield pathological tumor MPR (ypTMPR) and yield pathological LNs stage (ypN), Kaplan-Meier analyses demonstrated that there was a better PFS for the ypTMPR(+)/ypN(0) group, followed by ypTMPR(-)/ypN(0), ypTMPR(+)/ypN(0), and ypTMPR(-)/ypN(1+2) (P=0.01). The average PFS time was 35.7, 31.7, 29.4, and 28.7 months, respectively. After achieving MPR, the probability of local recurrence or distant metastasis was 7.3%, 25%, 23.5%, and 23.7%, respectively. In this real-world study, the combination of tumor and LNs responses was significantly associated with prognosis, and we demonstrated that ypTMPR(+)/ypN(0) group had a better prognosis, followed by ypTMPR(-)/ypN(0), ypTMPR(+)/ypN(0), and ypTMPR(-)/ypN(1+2). We advocate for ypTMPR(+)/ypN(0) status as a better surrogate of PFS in resectable NSCLC patients after NCIT.

To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%. To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials. MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients. Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded. Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis. Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%). This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.

Introduction: Lung cancer remains the top cancer killer worldwide, primarily due to advanced presentation. However, up to 40% of cases still present with early-stage disease. Previously, standard management for resectable stage II NSCLC typically involved surgery followed by adjuvant chemotherapy, however recent interest has grown around neoadjuvant therapies, particularly the combination of chemotherapy and immunotherapy. Although neoadjuvant chemoimmunotherapy is not yet a universal approach for early-stage NSCLC, it is under active investigation. This case of pathologic complete response following neoadjuvant chemoimmunotherapy demonstrates the potential benefits of such an approach for early-stage NSCLC, especially in patients with high PD-L1 expression, and supports the evolving role of immunotherapy in early stage NSCLC.Case: A 74-year-old Asian male with no history of smoking presented with shortness of breath and underwent a routine chest X-ray, which revealed a 6 cm mass in the left upper lobe (LUL). A follow-up chest CT scan confirmed a 5.6 x 5.2 x 6.4 cm mass in the LUL with associated ground-glass opacity. Image-guided biopsy confirmed lung adenocarcinoma, and next generation sequencing (NGS) testing revealed no targetable mutations and a PD-L1 expression of 100%. PET scan showed an increased SUV uptake in the primary tumor with no evidence of lymph node or distant metastases, and endobronchial ultrasound (EBUS) demonstrated negative mediastinal lymph node biopsies. The patient received three cycles of neoadjuvant chemoimmunotherapy with Nivolumab, Cisplatin, and Pemetrexed per the CheckMate 816 protocol. Following neoadjuvant treatment, he underwent a left video-assisted thoracoscopic (VATS) left upper lobectomy with mediastinal lymph node dissection of levels 5-12. Final surgical pathology showed no evidence of viable tumor cells, with all 21 lymph nodes negative for adenocarcinoma. His post-operative recovery was unremarkable and was discharged on POD 2. He is currently on surveillance CT scan protocols every 6 months with no evidence of disease recurrence. Discussion: This case highlights the efficacy of neoadjuvant chemoimmunotherapy in achieving a complete pathological response in early-stage NSCLC. The combination of Nivolumab, an immune checkpoint inhibitor, with Cisplatin and Pemetrexed, a platinum-based chemotherapy regimen, capitalizes on the synergy between immune activation and cytotoxic effects, improving the likelihood of complete tumor eradication prior to surgery. This approach is particularly relevant for patients who lack any actionable mutations which underscores the importance of expediting early preoperative NGS results. Our patient's response highlights the importance of providing more routine preoperative chemoimmunotherapy for earlier stage NSCLC patients to improve survival.

BackgroundLocally advanced non-small cell lung cancer (NSCLC) with N1/N2 lymph node metastasis is challenging with poor survival. Neo-adjuvant chemo-immunotherapy has gained benefits in a proportion of these patients. However no specific biomarker has been proved to predict the effect before therapy. In addition, the relationship of nodal status and survival after neo-adjuvant chemo-immunotherapy is still not well stated.MethodsA total of 75 resectable NSCLC patients with N1/N2 stage who received neo-adjuvant chemo-immunotherapy plus surgery were retrospectively studied. The clinical characteristics, surgical information and safety parameters were collected. The correlations of major pathological response (MPR) and pathological complete response (pCR) with clinical data were analyzed. The progression free disease(PFS) and overall survival(OS) were evaluated with pathological response and nodal status.ResultsOf the 75 patients, 69 (92%) patients experienced treatment related adverse effects, while grade 3–4 adverse effects occurred in 8 (10%) patients. All the patients received surgical R0 resection with a MPR rate of 60% and a pCR rate of 36%. 67% of N1 patients and 77% of N2 patients had nodal clearance after neo-adjuvant treatment. A significant difference was observed between pathological response with age, histology and multiple lymph node metastasis. The PFS was better in the MPR cohort. The PFS was 90.1% and 83.6% at the nodal clearance group at the time of 12 and 18 months, compared with 70.1% and 63.7% at the nodal residual group.ConclusionsThe neo-adjuvant chemo-immunotherapy for locally advanced NSCLC with nodal positive was safe and feasible. The patients with elder age and squamous-cell carcinoma (SCC) were more likely to have better pathological response, while multiple nodal metastasis was a negative predictor. The clearance of lymph node resulted in significantly longer PFS and OS.

6069 Background: Neoadjuvant chemoimmunotherapy has been an emerging hotspot for the treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), but the treatment response still requires improvement. Given the potential synergistic antitumor effects of dual inhibition of the PD-1/L1 and EGFR pathways, we proposed a novel neoadjuvant treatment regimen combining chemoimmunotherapy with EGFR-TKI, followed by adjuvant immunotherapy treatment, and evaluated the efficacy and safety of this approach. Methods: This open-label, single-arm, phase 2 trial was done at a tertiary hospital in China. Patients were eligible if they were aged at least 18 years old; had pathologically confirmed HNSCC with locally advanced disease according to the AJCC 8th Edition; had an ECOG performance status of 0−1; had at least one measurable target lesion according to RECIST 1.1 criteria; and had sufficient organ function. Patients with LA-HNSCC received two cycles of tislelizumab (200mg) and TP (nab-paclitaxel and cisplatin) chemotherapy, administrated on day one of each three-week cycle, along with afatinib (30mg) during the intermittent period between chemoimmunotherapy cycles, followed by 15 cycles of adjuvant tislelizumab treatment. The primary endpoint was the complete pathologic response (pCR) rate, defined as the percentage of patients with no detectable RVT cells in the resected primary tumor. Results: A total of 40 patients were enrolled and received neoadjuvant treatment, 32 of whom proceeded to surgical resection and achieved a pCR rate of 40.6% (95% CI: 23.7−59.4%). The overall response rate (ORR) was 82.5% (95% CI: 67.2−92.7%). The median follow-up time was 14.4 months (range: 2.4−27.6 months) . The estimated 1-year overall survival (OS) was 96.7% (95%CI: 90.5%−100%). No deaths occurred among patients who achieved pCR/MPR. The most common treatment-related adverse events (TRAEs) of any grade were alopecia (100%), followed by nausea (62.5%), lymphopenia (57.5%), diarrhea (55%), and rash (55%). The most common TRAE of grade 3−4 was lymphopenia (5/40, 12.5%). No treatment-related surgical delays were observed. Neoadjuvant treatment induced a significant increase in the proportion of peripheral CD8+ T cells, along with a reduction in B cells. TP53 wild-type patients were more likely to achieve a more favorable pathologic response compared to those with a TP53 mutation. A significant difference in oral microbial composition was found between patients with different pathologic responses. Conclusions: This study firstly reported the promising efficacy and acceptable safety profile of neoadjuvant chemoimmunotherapy combined with apatinib in the treatment of patients with LA-HNSCC. Further evaluation in large-scale clinical trials with longer follow-up periods is needed. Clinical trial information: NCT05516589 .

Background: Addition of the PD-1 inhibitor pembrolizumab to neoadjuvant chemotherapy improves pathologic complete response (pCR) rates and event-free survival in triple-negative breast cancer (TNBC). Immunotherapy may lead to immune-related adverse events (irAE), which can be life-threatening and permanent. Presence of tumor-infiltrating lymphocytes (TILs) in TNBC is also associated with improved prognosis and treatment response. Little data exists regarding associations between irAE and pCR, and between TILs and irAE, in TNBC. This study evaluates associations between irAE, clinicopathologic factors (including TILs), and pCR after neoadjuvant chemoimmunotherapy (NCIT) in a diverse single-institution cohort of TNBC patients (pts). Methods: Pts who received NCIT at our institution between 2021 and 2023 were identified from pharmacy database. Details of tumor stage, NCIT treatment, response to therapy, and presence or absence of irAE were obtained by chart review. IrAE were graded using Common Terminology Criteria for adverse events (CTCAE). Stromal TILs were estimated within the borders of the invasive carcinoma as per International TILs Working Group guidelines. Associations of age, race, ethnicity, tumor size (T stage), node involvement (N stage), grade, HER2 IHC status, TILs, and completion of planned NCIT with irAE incidence and pCR were assessed by Wilcoxon rank-sum tests for continuous variables and chi-square or Fisher’s exact tests for categorical variables. P-values &amp;lt;0.05 were considered statistically significant. Results: 46 pts were treated with NCIT [27 (58.7%) Black; 14 (30.4%) Hispanic]. Median age was 60.5 (range 33-88). All NCIT regimens included pembrolizumab and a taxane. 35 pts (76.1%) received doxorubicin, and 25 (54.3%) received carboplatin. 31 (67.4%) pts received 80% or more of their planned NCIT regimen. Reasons for early discontinuation were chemotherapy toxicity (8 pts), irAE (4), progression of disease (POD) (2), unknown (1). 13 pts (28.2%) developed at least 1 irAE, including hypothyroidism (3 pts), rash (3), adrenal insufficiency (2), hepatitis (2), arthritis (2), myositis, pneumonitis, pericarditis, panniculitis, and encephalitis (1 each). irAE was Grade 1-2 in 6 pts, Grade 3 in 5 pts, Grade 4 in 1 pt, and Grade 5 in 1 pt. 41 pts underwent surgery. Reasons for no surgery were POD (2 pts, included in response analysis), fatal irAE (1 pt), pt refusal (1 pt), and unknown (1 pt). Of 43 evaluable pts, 24 (55.8%) achieved pCR. Development of irAE (p=0.039), younger age (p=0.028), and Hispanic ethnicity (p=0.005) were associated with pCR. Black pts were less likely to achieve pCR compared to non-Black pts (p=0.003). T and N stage, tumor grade, HER2 IHC status, and completion of planned NCIT were not associated with pCR. TILs were associated with achievement of pCR (p=0.002), but not with presence of irAE (p=0.341). No associations between irAE and age, race, ethnicity, T or N stage, tumor grade, HER2 IHC status, and completion of planned NCIT were seen.Conclusion: In this diverse cohort of TNBC pts, TILs and irAE, as well as age, race, and ethnicity, were associated with achievement of pCR to NCIT, while tumor stage and grade, and completion of planned NCIT, were not. No predictive factors for development of irAE were seen. Citation Format: Michelle Sterpi, Yungtai Lo, Susan Fineberg, Harjot Gill, Della Makower. Impact of Immune-Related Adverse Events on Response to Neoadjuvant Chemoimmunotherapy in Triple Negative Breast Cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-11-20.

Background: This study aims to investigate the effectiveness of neoadjuvant chemoimmunotherapy (NACI) regimens in treating advanced oral squamous cell carcinoma (OSCC). Methods: We analyzed clinicopathologic features of advanced OSCC patients who received PD-1 inhibitors in combination with carboplatin and paclitaxel before surgical tumor resection between 2020 and 2022. The Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) and pathologic response were used to evaluate the efficacy of the NACI treatment. Adverse events apparently related to NACI treatment were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier survival curves and compared using the log rank test. Additionally, we calculated the area under curve (AUC) to compare the predictive value of PD-L1 expression with baseline serum lipid biomarkers for patient response. Results: Our analysis involved 104 advanced OSCC patients who received NACI. Notably, the top three grade 1-2 treatment-related adverse events (TRAEs) were Alopecia (104; 100%), Anemia (81; 77.9%) and Pruritus (62; 59.6%). Only one patient developed grade 3-4 TRAEs due to increased aminotransferases. The pathological complete response (PCR) rate was 47.1%, and the major pathological response (MPR) rate was 65.4%. Importantly, patients achieving MPR exhibited higher CPS. The diagnostic value of CPS as a biomarker for NACI efficacy was enhanced when combined total cholesterol (TC) level. Our findings from DFS and OS suggested that patients who underwent NACI before surgery experienced improved survival compared to those who accepted the surgery alone. Conclusions: The data from this study proved evidence that NACI treatment is safe and encouragingly efficacious in treating advanced OSCC patients. Citation Format: Jinsong Li, Bowen Li, Shule Xie, Haotian Cao, Zhaoyu Lin, Qunxing Li, Song Fan. Response to neoadjuvant chemoimmunotherapy in resectable locally advanced oral squamous cell carcinoma: a single-center retrospective observational study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5091.

Resectable non-small cell lung cancer (NSCLC) patients have a high risk of recurrence. Multiple randomized controlled trials (RCTs) have shown that neoadjuvant chemo-immunotherapy brings new hope for these patients. The study aims to evaluate the safety, surgery-related outcomes and oncological outcomes for neoadjuvant chemo-immunotherapy in real-world setting with a large sample size and long-term follow-up. Patients with clinical stage IB-IIIB NSCLC who received neoadjuvant chemo-immunotherapy at two Chinese institutions were included in this retrospective cohort study. Surgical and oncological outcomes of the enrolled NSCLC patients were collected and analyzed. There were 158 patients identified, of which 124 (78.5%) were at stage IIIA-IIIB and the remaining 34 (21.5%) were at stage IB-IIB. Forty-one patients (25.9%) received two cycles of neoadjuvant treatment, 80 (50.6%) had three cycles, and 37 (23.4%) had four cycles. Twenty-four patients (15.2%) experienced grade 3 or worse immune-related adverse events. The median interval time between the last neoadjuvant therapy and surgery was 37 [interquartile range (IQR), 31-43] days. Fifty-eight out of 96 (60.4%) central NSCLC patients who were expected to undergo complex surgery had the scope or the difficulty of operation reduced. Ninety-five (60.1%) patients achieved major pathologic response (MPR), including 62 (39.2%) patients with pathologic complete response (pCR). Multivariate regression analysis showed that no clinical factor other than programmed death-ligand 1 (PD-L1) expression was predictive of the pathological response. The median follow-up time from diagnosis was 27.1 months. MPR and pCR were significantly associated with improved progression-free survival (PFS) and overall survival (OS). Neither stage nor PD-L1 expression was significantly associated with long-term survival. The neoadjuvant chemo-immunotherapy is a feasible strategy for NSCLC with a favorable rate of pCR/MPR, modified resection and 2-year survival. No clinical factor other than PD-L1 expression was predictive of the pathological response. pCR/MPR may be effective surrogate endpoint for survival in NSCLC patients who received neoadjuvant chemo-immunotherapy.