tbuckley/cabot-search huggingface dataset:
Efficacy and safety of perioperative, neoadjuvant or adjuvant immunotherapy alone or in combination chemotherapy in early-stage non-small cell lung cancer: A systematic review and meta-analysis of randomized clinical trials.
Authors: Hongbing Liu, Yunchang Meng
Journal: Journal of Clinical Oncology (2024)

8025 Background: Adjuvant (AD), neoadjuvant(NE), or perioperative(PE) immunotherapy in early-stage non-small cell lung cancer (eNSCLC) has been validated in multiple clinical trials in recent years. However, the comparations of efficacy and safety among three treatment modalities remain unclear. Methods: The PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) of immune checkpoint inhibitors (ICI) plus chemotherapy (CT) for eNSCLC. We calculated hazard ratios (HRs) or advantage ratios (ORs) for binary endpoints with 95% confidence intervals (CIs). Network meta-analysis was performed using a Bayesian framework to indirectly compare the three treatment modalities. Results: A total of 11 RCTs (2 NE, 6 PE, and 3 AD) including 6951 NSCLC patients were included. Among the three treatment modalities, indirect comparisons revealed that efficacy differed between PE and AD immunotherapy was only observed in the EFS/DFS (HR=0.68, 95%CI: 0.49-0.89). Compared with the control group, NE/PE immunotherapies significantly improved pathologic complete response (pCR) (OR=7.56, 95%CI: 5.24-10.92), major pathologic response(MPR) (OR=5.46, 95%CI: 3.97-7.51), EFS(HR=0.58, 95% CI: 0.50-0.67), and AD immunotherapy significantly improved DFS (HR=0.83, 95% CI: 0.73-0.94). No significant OS difference was observed in NE and AD setting (HR=0.62, 95% CI: 0.36-1.05; HR=0.90, 95% CI: 0.76-1.06, respectively), and only PE immunotherapy showed OS benefits(HR=0.67, 95%CI: 0.54-0.84). In addition, EFS was significantly improved in the PE treatment subgroup regardless of stage, pathologic response, histology, PD-L1 expression, and gender (Table), but no significant benefit in the EGFRm NSCLC subgroup(HR=0.54, 95% CI: 0.21-1.43). AD (OR 1.52, 95% CI: 1.01-2.30) and PE (OR 1.29, 95% CI: 1.08-1.54) immunotherapies were significantly associated with higher grade ≥3 adverse events (AEs) compared with controls. Rash was the most common grade ≥3 irAEs. Conclusions: PE immunotherapy seems to be more effective than NE and AD immunotherapy in three treatment modes. NE and PE immunotherapy significantly improved pCR, MPR, EFS, and AD immunotherapy significantly improved DFS in eNSCLC patients in comparison with the control group, but only PE immunotherapy significantly improved OS. [Table: see text]
Surgical outcomes in patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy versus chemotherapy alone: A systematic review and meta-analysis.
Authors: Riona Aburaki, Yu Fujiwara, Kohei Chida, Nobuyuki Horita, Misako Nagasaka
Journal: Journal of Clinical Oncology (2024)

8020 Background: Neoadjuvant immune checkpoint blockade (ICB) including programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in combination with chemotherapy has been shown to improve survival outcomes in patients with early-stage non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated yet. We aimed to compare surgical outcomes between neoadjuvant chemoimmunotherapy with PD-1/PD-L1 blockade and chemotherapy alone in patients with resectable NSCLC. Methods: We performed a systematic search of PubMed and Embase for randomized-controlled trials (RCTs) that compared neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with resectable NSCLC and reported surgical outcomes including surgical resection rates, R0 resection rates, postoperative complications, any-grade treatment-related adverse events (TRAEs), grade 3-5 TRAEs, serious AEs (SAEs), and AEs leading to cancellation of surgery. Meta-analysis was performed using the random-effects model to pool odds ratios (ORs) of these surgical and safety outcomes. Heterogeneity among the included studies for each outcome was assessed using I 2 statistics and high heterogeneity was defined as I 2 higher than 50%. Results: A systematic review identified 5 RCTs with 2,069 patients for a meta-analysis. All identified RCTs evaluated combination of neoadjuvant PD-1/ PD-L1 blockade with chemotherapy versus chemotherapy alone. Chemoimmunotherapy was associated with an improvement in R0 resection rates (OR 1.72, 95% CI 1.22 - 2.42; p = 0.002), whereas surgical resection rates were comparable between two groups (OR 1.51, 95% CI 0.90 - 2.51; p = 0.12). No significant difference was observed for complication rates, any-grade TRAEs, grade 3-5 TRAEs, SAEs, or AEs leading to cancellation of surgery. (Table). Conclusions: Although the surgical resection rate itself was not significantly different between neoadjuvant chemoimmunotherapy and chemotherapy alone, neoadjuvant chemoimmunotherapy was associated with increased R0 resection rates without an increase in the incidence of complications, TRAEs, and cancellation of surgery. This indicates that neoadjuvant chemoimmunotherapy can be safely administered with an increase in R0 resection rate, which potentially leads to improvement of survival outcomes in patients with resectable NSCLC. [Table: see text]
Epcoritamab with rituximab + lenalidomide (R<sup>2</sup>) in previously untreated (1L) follicular lymphoma (FL) and epcoritamab maintenance in FL: EPCORE NHL-2 arms 6 and 7.
Authors: Leslie A. Lori, Lorenzo Falchi, Joost S.P. Vermaat, Gerardo Musuraca, David Belada, Marcel Nijland, Jacob Haaber Christensen, Fritz Offner, Daniela Hoehn, Jennifer Marek, Liwei Wang, JP Mei, Pau Abrisqueta, Joshua D. Brody
Journal: Journal of Clinical Oncology (2024)

7014 Background: In 1L FL, more effective, less toxic treatment (tx) options that induce durable complete responses (CRs) are needed. For responders, novel maintenance approaches are needed to improve long-term outcomes. We present data from EPCORE™ NHL-2 (phase 1/2; NCT04663347), with longer follow-up for epcoritamab + R 2 in 1L FL (arm 6) and the first disclosure for epcoritamab maintenance in patients (pts) with FL in CR or partial response (PR) after 1–2 lines of standard of care (SOC) tx (arm 7). Methods: Adults with CD20 + FL grade (G) 1–3A received subcutaneous epcoritamab 48 mg. In arm 6, pts received R 2 for ≤12 cycles (Cs) of 28 d and epcoritamab (QW, C1–2; Q4W, C3–26). In arm 7, pts received epcoritamab (QW, C1 [28 d]; Q8W, C2–13 [56 d/C]). Pts received step-up epcoritamab dosing and corticosteroid prophylaxis in C1 to mitigate CRS. Primary endpoints were overall response rate (ORR; Lugano criteria) in arm 6 and safety/tolerability in arm 7. Results: As of Nov 22, 2023, 41 pts with 1L FL received epcoritamab + R 2 (arm 6) and 20 pts in CR or PR after SOC tx received epcoritamab maintenance (arm 7). In arm 6 (median follow-up, 21.1 mo), median age was 57 y and 34% had FLIPI 3– 5. ORR was 95%; CR rate was 85%. The most common treatment-emergent AEs (TEAEs) were COVID-19 (63%), CRS (56%), and neutropenia (56%). CRS was low grade (41% G1, 15% G2) and resolved; most events occurred after the first full dose and none led to epcoritamab discontinuation. Two fatal TEAEs occurred (COVID-19 pneumonia and septic shock). In arm 7 (median follow-up, 19.7 mo), median age was 54.5 y and 25% had FLIPI 3–5; 60% had CR and 40% had PR with their last tx line. All pts had prior anti-CD20 tx, 80% had prior alkylating agents, and 50% had prior anthracyclines; 80% had 1 prior tx line. The most common TEAEs were COVID-19 (70%) and CRS (55%). CRS was G1 (40%) or G2 (15%) and resolved; events mostly occurred after the first full dose, and none led to tx discontinuation. One fatal TEAE occurred (respiratory failure; post-acute COVID syndrome after 2 Cs of tx). No ICANS or clinical tumor lysis syndrome occurred in either arm. Additional efficacy data are in Table. Conclusions: In arm 6, epcoritamab + R 2 continued to show deep, durable responses in 1L FL; safety was manageable and consistent with prior reports. In arm 7, the first epcoritamab maintenance data in FL showed conversions from PR to CR, with manageable safety and no new safety signals. The data warrant further evaluation of epcoritamab-based, chemotherapy-free regimens in FL. Clinical trial information: NCT04663347 . [Table: see text]
Efficacy and safety of immunotherapy plus chemotherapy for lung cancer neoadjuvant treatment: A network meta-analysis based on randomized controlled trials.
Authors: Shen Li, Jiaqing Yang, Chenhao Xu, Xuelei Ma
Journal: Journal of Clinical Oncology (2024)

8026 Background: With immunotherapy's swift progress in lung cancer treatment, combining immunotherapy with chemotherapy (CT) for neoadjuvant use has attracted significant interest, though direct comparisons of its efficacy and safety are still scarce. This study aims to comprehensively evaluate the efficacy and safety of immunotherapy combined with chemotherapy versus chemotherapy alone in the neoadjuvant treatment of lung cancer. Methods: We searched databases, including PubMed and EMBASE, for phase II and III randomized global trials that assessed neoadjuvant lung cancer treatment with immunotherapy combined with chemotherapy. We performed a Bayesian random-effects network meta-analysis to evaluate efficacy, presenting Hazard Ratios (HRs) and 95% Confidence Intervals (95%CI). Bias risk was determined using the Cochrane risk of bias tool, and evidence quality was appraised via the CINeMA framework. Results: Our analysis included eight randomized controlled trials, comprising a total of 3,316 patients. The results indicated that, compared to neoadjuvant chemotherapy alone, the Event-Free Survival (EFS) was highest for the durvalumab+CT group, ranking first with an HR of 2 (95% CI: 1.0 to 3.7). The pembrolizumab+CT group ranked second with an HR of 1.8 (95% CI: 0.76 to 4.2), followed by the nivolumab+CT group in third place with an HR of 1.7 (95% CI: 0.95 to 3.1). Both the nivolumab and ipilimumab+CT and toripalimab+CT groups tied for fourth place with HRs of 1.4 (95% CI: 0.58 to 3.5) and 1.5 (95% CI: 0.70 to 3.2), respectively. The camrelizumab+CT group had the lowest EFS ranking, with an HR of 1.7 (95% CI: 0.74 to 3.8). The combination of nivolumab+ipilimumab+CT showed the most favorable outcomes in terms of Pathologic Complete Response (PCR) and R0 resection rates among the six treatments, with lnOR values of 3.17 and 1.48, respectively. This combination also had the lowest occurrence of treatment-related adverse events greater than grade 3, with an lnOR value of -1.38. Conclusions: This network meta-analysis indicates that durvalumab, when combined with chemotherapy, offers the best EFS among the immunotherapy options evaluated, demonstrating good safety and efficacy. Concurrent use of nivolumab and ipilimumab resulted in the highest pCR and R0 resection rates. Moreover, for patients with lung cancer, the preliminary evidence supports the value of combining immunotherapy with chemotherapy as a neoadjuvant treatment strategy over chemotherapy alone. [Table: see text]
Deep-learning model for real-time prediction of recurrence in early-stage non-small cell lung cancer: A multi-modal approach.
Authors: Hyun Ae Jung, Daehwan Lee, Boram Park, Kiwon Lee, Ho Yun Lee, Tae Jung Kim, Yeong Jeong Jeon, Junghee Lee, Seong Yong Park, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2024)

8029 Background: The surveillance protocol for early-stage non-small cell lung cancer (NSCLC) is not contingent upon individualized risk factors for recurrence. Longitudinal risk calculation for the prediction of recurrence was based on circulating tumor DNA. This study aimed to develop a deep-learning model using comprehensive data from clinical practice for practical longitudinal monitoring. Methods: A multi-modal deep-learning model employing transformers was developed for real-time recurrence prediction using clinical, pathological, and molecular data at baseline, alongside longitudinal laboratory, and radiologic data during surveillance. Patients with histologically confirmed NSCLC (stage I-III) undergoing curative intent surgery between January 2020 and September 2022 were included. The collected data was divided into training, validation, and test sets in a 6:2:2 ratio. The primary outcome focused on predicting likelihood of recurrence within one year from the monitoring point. This study demonstrated the timely provision of risk scores (RADAR score), determined thresholds, and the corresponding Area Under the Curve (AUC). Results: A total of 14,345 patients were enrolled (10,262 with stage I, 2,380 with stage II, and 1,703 with stage III). The training, validation, and test sets comprised 8,578, 2,866, and 2,901 patients, respectively. The model incorporated 64 clinical-pathological-molecular factors at baseline, alongside longitudinal laboratory, and radiologic text data. Radiologic data of 177,246 was used (mean 12.4 chest CT scan per patient) during surveillance. Baseline RADAR score was 0.20 (standard deviation [Std] 0.17) in stage I, 0.51 (Std 0.20) in stage II, and 0.64 (Std 0.19) in stage III. The AUC for predicting relapse within one year from that monitoring point was 0.847 across all stages with the sensitivity of 80.6% and specificity of 74.4% (Table) (AUC=0.851 in stage I, AUC=0.763 in stage II, and AUC=0.721 in stage III). Conclusions: This pilot study introduces a deep-learning model utilizing multi-modal data from routine clinical practice for predicting relapse in early-stage NSCLC. It demonstrates the timely provision of risk score, RADAR score, to clinicians for recurrence prediction, potentially guiding risk- adapted surveillance strategies and aggressive adjuvant systemic treatment. Notably, the RADAR score exhibited a high prediction ability for relapse in stage I disease. [Table: see text]
Smoking history requirement and lung cancer (LC) screening (LCS) eligibility disparities.
Authors: Matthew Smeltzer, Wei Liao, Carrie Fehnel, Jordan Goss, Talat Qureshi, Sara Peppers, Meredith Ray, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2024)

8016 Background: LCS eligibility criteria are not optimal. US Preventive Services Task Force 2021 criteria (USPSTF21) expanded eligibility, but race and sex disparities persist. We evaluated how 4 modified criteria impact LCS eligibility. Methods: We analyzed data from all persons enrolled into LCS and a non-screening detected Lung Nodule Program (LNP) in a prospective community-based cohort. The LNP used Fleischner Society guidelines. We compared sex, race, and Area Deprivation Index (ADI) of LCS-eligible persons and LC patients diagnosed based on USPSTF21 (Age 50-80, 20 pack-years [PY], 15 year quit duration [QD]) versus 4 more-relaxed smoking history criteria in LNP including the new American Cancer Society (ACS) criteria (Group 4, Table). Results: Of 38,740 individuals from 2015-2023, 11,886 had LCS and 26,854 were from LNP. Expanded criteria increased the total eligible over USPSTF21 from 3939, to 4572, 4611, 4950, 5747 in Groups 2-5, respectively. LC was detected in 3.7% of LDCT (17.4% of those with Lung-RADS 3/4), and in 21%, 20%, 19%, 19%, and 18% of LNP Groups 1-5; number needed to treat (NNT) was 26.8 (LDCT), 5.8 (LDCT Lung-RADS 3/4), and 4.9, 4.9, 5.2, 5.2, 5.5 in Groups 1-5. LC was most frequently adenocarcinoma (41-51%) or squamous (21-30%); with similar stage across groups (47-48% stage I/II). LC was diagnosed in 17%, 11%, 14%, and 13% of additional eligible persons vs. 21% in USPSTF21 (Table). The additional eligible individuals with LC were 42%, 58%, 40%, and 46% female in Groups 2-5. We compared % female in Group 3 with LNP (58 v 51%, p=.25) and LCS (58 v 52%, p=.22). In terms of race, additional eligible individuals were 11%, 47%, 10%, and 24% Black in Groups 2-5; with significant differences between Group 3 and both LNP (47 v 25%, p&lt;.001) and LCS (47 v 16%, p&lt;.001) cohorts. These groups (2-5) were 26%, 38%, 29%, and 33% in the highest (poorest) ADI quintile, with no differences between Group 3 and LNP (38 v 36%, p=.66) or LCS (38 v 42%, p=.56). Group 3 / 5 criteria yielded a 17% / 46% increase in persons screened, and a 9.5% / 28% increase in LC identified over USPSTF21. Conclusions: Relaxed smoking history requirements provided better access to LCS while maintaining diagnostic efficiency in terms of NNT. The shift from 20 PY to 20 years reduced race- and sex- based disparities in LCS eligibility and LC diagnosis, while still reaching the most socially disadvantaged groups. [Table: see text]
Efficacy and safety of ibrutinib plus venetoclax in patients with mantle cell lymphoma (MCL) and <i>TP53</i> mutations in the SYMPATICO study.
Authors: Michael Wang, Wojciech Jurczak, Marek Trneny, David Belada, Tomasz Wrobel, Nilanjan Ghosh, Mary-Margaret Keating, Tom van Meerten, Rubén Fernández-Álvarez, Gottfried von Keudell, Catherine Thieblemont, Frederic Peyrade, Marc Andre, Marc Hoffmann, Maoko Naganuma, Edith Szafer-Glusman, Jennifer Lin, James P. Dean, Jutta Katrin Neuenburg, Constantine S. Tam
Journal: Journal of Clinical Oncology (2024)

7007 Background: TP53 mutations confer high risk of early progressive disease (PD) and poor outcomes with standard chemoimmunotherapy in patients (pts) with MCL. To date, data on novel treatment options for these pts are limited to small single-arm analyses. The phase 3 SYMPATICO study is evaluating ibrutinib (Ibr) + venetoclax (Ven) in 3 cohorts of pts with MCL. Primary analysis of the randomized phase showed superior PFS with Ibr+Ven vs Ibr+placebo (Pbo) in pts with relapsed/refractory (R/R) MCL (Wang M et al, ASH 2023) with similar hazard ratios for pts with and without TP53mutations (0.57 [95% CI, 0.33–0.97] and 0.52 [95% CI, 0.32–0.82], respectively). Here, we report efficacy and safety of Ibr+Ven in pts with TP53 mutations across cohorts. Methods: The SYMPATICO cohorts are: open-label safety run-in phase to evaluate concurrent initiation of Ibr+Ven in R/R MCL (n=21); randomized phase to evaluate Ibr+Ven (n=134) vs Ibr+Pbo (n=133) in R/R MCL; and open-label cohort to evaluate first-line (1L) Ibr+Ven (n=78). Data were pooled across cohorts for pts with TP53mutations treated with oral Ibr 560 mg once daily and Ven (5-wk ramp-up to 400 mg once daily) for 2 y, then single-agent Ibr 560 mg until PD or unacceptable toxicity. Response was assessed by investigators per Lugano criteria. Results: In total, 74 pts with TP53 mutations received Ibr+Ven in the safety run-in phase (n=5), the randomized phase (n=40), and the 1L cohort (n=29). At baseline, median age was 67 y, 96% of pts had ECOG PS of 0–1, 43% had high-risk simplified MIPI score, 36% had bulky disease ≥5 cm, 64% had bone marrow involvement, and 39% had splenomegaly. With a median time on study of 40.1 mo (range, 0.6+ to 60.7), median PFS was 20.9 mo vs not reached (NR) in pts without TP53 mutations. ORR was 84%, and the CR rate was 57%. Median OS was 47.1 mo. Outcomes were generally comparable in 1L and R/R MCL (Table). Median duration of treatment was 15.9 mo (range, 0.3–58.9); at data cutoff, treatment was ongoing with Ibr in 24% of pts and with Ven in 4%. The most frequent grade ≥3 AEs (in ≥10% of pts) were neutropenia (32%), anemia (15%), and thrombocytopenia (15%). Conclusions: Ibr+Ven demonstrated promising efficacy with high CR rates and durable remissions in high-risk pts with MCL and TP53mutations in SYMPATICO (n=74; 29 1L and 45 R/R), the largest single-study cohort of such pts reported to date. Clinical trial information: NCT03112174 . [Table: see text]
Combining SBRT with GM-CSF and Peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors.
Authors: Min Fan, Boyan Wang, Jiayan Chen, Junmiao Wen, Huiting Li
Journal: Journal of Clinical Oncology (2024)

8112 Background: After the failure of multi-line treatment, patients with stage Ⅳ thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m 2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 20 patients from March 2021 to September 2022, were enrolled in this trial, with 1 (5.0%) type A thymoma, 2 (10.0%) type B1 thymoma, 2 (10.0%) type B2 thymoma, 1 (5.0%) type B3 thymoma, 12 (60.0%) thymic squamous cell carcinoma and 2 (10.0%) thymic neuroendocrine tumor. At a median follow-up of 18.6 months, 8 (40.0%) out of 20 patients had abscopal effects, and the ORR was 45.0%. The median OS had not been attained yet. The median PFS was 9.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects (Figure 1). 3 patients (15.0%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0), among which cardiac insufficiency compelled 1 patient (5.0%) to drop out of treatment. Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage Ⅳ thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .