tbuckley/cabot-search huggingface dataset:
Efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine in elderly pre-treated patients with metastatic non-small-cell lung cancer.
Authors: Lin Li, Yue Yuan, Jiayi Gao, Ping Zhang, Xiaonan Wu, Min Tang, Xin Nie, Di Ma, Zhe Zhao, Yumeng Tian
Journal: Journal of Clinical Oncology (2024)

e20556 Background: The subsequent therapy of elderly non-small cell lung cancer (NSCLC) without driver oncogene has always been a challenge due to the poor performance status and multiple comorbidities, especially in those who acquired resistance to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] blockade. Metronomic chemotherapy (MCT) is the frequent administration of chemotherapy drugs at lower doses each time which shows a better safety profile, antitumor angiogenesis, and immune modulatory effects compared with traditional chemotherapy. Here we designed an observational study to evaluate the efficacy and safety of PD-1 inhibitors plus metronomic oral vinorelbine(mOV) in elderly pre-treated metastatic NSCLC. Methods: Patients aged 65 years and above who had been histologically or cytologically confirmed unresectable stage III and IV NSCLC were recruited for this study. All the pts had no EGFR mutation, ALK fusions, or ROS1 fusions and received at least one systematic treatment. Pts received PD-1 inhibitors combined with mOV (30mg, TIW1, day 1-3-5 per week) for 6 cycles, followed by PD-1 inhibitors maintenance until disease progression or intolerable toxicities. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: From May 2020 to June 2023, 23 pts were enrolled in the study. The median age was 70 with 18(78%) males. Median follow-up time was 22.8 months (range 3.9months-41.9months). The median PFS was 5.13 months (95%Cl: 3.1 months-7.1 months) and the median OS was 28.1 months (95%Cl: (15.2 months-NA). The ORR and DCR were 13% (95%C1: 1.44%-27.6%) and 69.6% (95%Cl: 49.2%-89.9%), respectively. The PFS (p = 0.459, HR = 0.671 95%CI 0.233-1.932) and OS (p = 0.483, HR = 1.607 95%CI 0.426-6.056) were similar between those pts who previously received immunotherapy (N = 16, 69.5%) and not. PD-L1 TPS didn’t affect the patient’s PFS (&lt;1% vs≥1%, p = 0.078, HR = 2.648 95%CI 0.895-7.835 ) and OS(&lt;1% vs≥1%, p = 0.306, HR = 2.202 95%CI 0.485-9.989). Adverse events (AEs) of any grade were observed in 20(86.9%) pts of which grade III-IV AEs occurred in 4 (17.4%) pts. These grade III-IV events consisted of interstitial pneumonia, pulmonary infection, leukopenia, and neutropenia. Immune-related adverse events (irAEs) occurred in 4 (17.4%) pts, of which grade III irAEs occurred in 2 (8.7%) patients with interstitial pneumonia. No grade 4 irAEs and grade 5 adverse events even occurred. Conclusions: The regimen of PD-1 inhibitors plus mOV for the subsequent therapy showed good overall survival benefits and safety in elderly patients with metastatic NSCLC without driver oncogene which suggests it is worth further exploration.
Development of a novel granulocyte scoring system for use as a predictive/prognostic biomarker in patients with advanced melanoma undergoing treatment with combination immunotherapy.
Authors: Max Julve, Yien Ning Sophia Wong, Margarita Diez de los Rios Riobo, Yago Garitaonaindia, Diana I. Rosero, Jazmine Needham, Juan Jose Soto, Chloe Beland, Ha Mo Linh Le, James Larkin, Andrew J.S. Furness
Journal: Journal of Clinical Oncology (2024)

9551 Background: Despite the implementation of immune checkpoint inhibition (ICI) for patients with metastatic melanoma, there remains an unmet clinical need for predictive/prognostic biomarkers to determine, from outset, which patients will derive benefit. Recent literature has suggested a significant role for granulocyte subsets in the development of resistance to systemic therapies, with an associated role in adaptive immunity. Methods: We sought to establish a novel immunological scoring system to use as a predictive/prognostic biomarker in patients with advanced melanoma being treated with ICI. In this retrospective, single centre study evaluating patients with advanced melanoma treated with combination ipilimumab and nivolumab, progression free survival (PFS) and overall survival (OS) were compared between groups defined by neutrophil, lymphocyte, eosinophil, monocyte and basophil counts. Data from 226 patients was collected at baseline, week 3, week 6, first response scan and at progression. Baseline and week 3 data was the focus of this primary analysis. Kaplan-Meier estimation and Cox regression analysis were performed. Results: Univariate analysis demonstrated that absolute neutrophil, eosinophil and basophil count strongly associates with PFS and OS outcomes at week 3. Combination of these counts into a novel neutrophil to eosinophil + basophil ratio (NEBR, (N/(E+B)) was assessed as a scoring system. High NEBR was associated with poorer PFS and OS at baseline and week 3 with consistently superior predictive/prognostic value than the well-established neutrophil to lymphocyte ratio (NLR). After accounting for covariates including concurrent steroids, infection and LDH, high NEBR remained significantly associated with worse PFS at baseline and poorer PFS and OS at week 3. Conclusions: Our findings highlight NEBR as a novel immunotherapeutic predictive/prognostic biomarker with potential clinical utility that warrants further investigation in patients with advanced melanoma and across other tumour groups. Further validation will be required through independent external datasets. [Table: see text]
Camrelizumab plus apatinib and temozolomide as first-line therapy for advanced acral melanoma: 2-year survival results from CAP 03.
Authors: Junjie Gu, Bin Lian, Lili Mao, Caili Li, Xue Bai, Li Zhou, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Xuan Wang, Bixia Tang, Xieqiao Yan, Siming Li, Yan Kong, Jie Dai, Xiaoting Wei, Juan Li, Jun Guo, Lu Si
Journal: Journal of Clinical Oncology (2024)

9547 Background: Acral melanoma is the predominant subtype in Asia, which presents with aggressive biological behavior. First-line immunotherapy yields modest efficacy in advanced acral melanoma, suggesting the need of combination therapy. Our CAP 03 study investigated the combination of anti-PD-1 antibody plus antiangiogenic agent and chemotherapy for the first-line treatment of advanced acral melanoma, and the primary analysis has been published on JAMA Oncology in June 2023 (objective response rate [ORR], 64%; median progression-free survival [PFS], 18.4 months). Here we updated the efficacy results with a median follow-up of 30.3 months (95% CI, 28.9-32.5; reverse Kaplan-Meier method) at data cutoff date on January 8, 2024. Methods: In this single-center phase 2 trial (NCT04397770), patients with pathologically confirmed unresectable stage III or IV acral melanoma and without prior systemic therapy for advanced disease were recruited. Patients received first-line intravenous camrelizumab (200 mg once every 2 weeks) plus oral apatinib (250 mg once a day) and intravenous temozolomide (200 mg/m 2 once a day on days 1-5 every 4 weeks) until disease progression or intolerable toxicity. The primary endpoint was ORR per Response Evaluation Criteria In Solid Tumors, version 1.1. Imaging assessment was performed after 4 weeks, then every 8 weeks until one year, and every 3 months thereafter. Overall survival (OS) was followed every 3 months. Results: Between May 2020 and August 2021, a total of 50 patients were enrolled. The confirmed ORR was 66.0% (33 of 50; 95% CI, 51.2%-78.8%). The median PFS was 21.2 months (95% CI, 10.1-27.1). The median OS was not reached, and the 1-year and 2-year OS rates were 88.0% (95% CI, 75.2%-94.4%) and 64.8% (95% CI, 49.5%-76.5%), respectively. Further analyses indicated comparable PFS benefit in subgroups by age (&lt;65 years vs ≥65 years), sex (male vs female), Eastern Cooperative Oncology Group performance status (0 vs 1), NRAS status (variant vs wild-type), stage, lactic dehydrogenase (LDH) level, and PD-L1 combined positive score (&lt;5 vs ≥5). Regarding OS, similar trends were observed in these subgroups, except that patients with normal LDH had better median OS than those with elevated LDH (not reached vs 22.6 months, log-rank nominal P=0.033). Conclusions: This first-line triplet combination shows encouraging survival benefits in patients with advanced acral melanoma, regardless of NRAS status or PD-L1 expression level. Follow-up is still ongoing to obtain mature OS data. Clinical trial information: NCT04397770 .
Stage IV non-small cell lung cancer in Veterans undergoing lung cancer screening who were not prescribed statins despite U.S. Preventative Services Task Force recommendations.
Authors: Zane Elfessi, Catherine Dell, Israel Rubinstein
Journal: Journal of Clinical Oncology (2024)

e20583 Background: It is well established that Veterans eligible for lung cancer screening (LCS) are also at risk of atherosclerotic cardiovascular disease (ASCVD) due to smoking. Current concepts suggest that statins could play a role in lung cancer prevention and treatment. Accordingly, the purpose of this retrospective, quality improvement project was to determine whether newly diagnosed stage IV non-small cell lung cancer (NCSLC) rate is higher in Veterans undergoing LCS who were not prescribed statins despite U.S. Preventative Services Task Force (USPSTF) recommendations. Methods: Electronic health records of Veterans undergoing LCS and subsequently diagnosed with NSCLC at the Jesse Brown VA Medical Center, Chicago, Illinois between 2021 and 2023 were reviewed. In each case, pertinent demographic, clinical, pathological, and pharmacy data were retrieved. The American College of Cardiology’s ASCVD Risk Estimator was used to assess the Veteran’s 10-year risk for a first ASCVD event. Data are presented as means ± SD. Statistical analysis was performed using Student’s t- and chi-squared tests as indicated. P &lt; 0.05 was considered statistically significant. Results: Out of 57 Veterans diagnosed NSCLC, 33 (all males; 71±6 years; 28 African Americans) were prescribed and 24 (21 males, 3 females; 70±7 years; 18 African Americans) were not prescribed statins. Body mass index was similar in both groups (26.6±6.0 and 26.0±6.0 kg/m 2 , respectively; p = 0.73). Twenty one out of 24 Veterans (88%) not prescribed statins were eligible according to USPSTF recommendations (10-year calculated risk, 15.23%±6.9%). Stage IV NSCLC was diagnosed in 7/33 (21%) Veterans prescribed statins and in 10/21 (48%) USPSTF-eligible Veterans not prescribed statins (p &lt; 0.05). Conclusions: Clinicians should assess the needfor a statin for primary prevention of ASCVD in each Veteran undergoing LCS. Stage IV NSCLC is more prevalent in Veterans with ASCVD risk who were not prescribed statins despite USPSTF recommendations. A larger, multi-site study is warranted to support or refute these initial observations.
Correlation of previous local vaccination site “flares” during immunotherapy for metastatic melanoma with complete responses to therapy.
Authors: Kimberly Leticia Loo, Barbara Ting-wen Ma, Anna C. Pavlick
Journal: Journal of Clinical Oncology (2024)

e21534 Background: mRNA vaccines have been shown to stimulate T-cells targeting patient-specific tumor neoantigens. When combined with immune checkpoint inhibitors (ICI) in a randomized Phase II trial, mRNA vaccines demonstrated improvement in recurrence free survival and distant metastasis free survival compared to ICI alone. We retrospectively examined patients (pts) with advanced melanoma treated more than 5 years ago on clinical trials with adjuvant NYESO1 or mRNA vaccine therapies (VT) then ICI upon recurrence and analyzed biomarkers correlating with treatment response. Methods: This retrospective study examined 22 pts with advanced melanoma treated between 2004-2017 with adjuvant vaccine therapies (VT). 10 of the 22 pts subsequently developed recurrent disease and were treated with ICI. We evaluated disease free interval following ICI, sex, age, BRAF status, HLA type, site of primary and metastatic disease, initial vaccine treatment, vaccine toxicities, stage and sites of melanoma recurrence, ICI treatment, response and toxicities, vaccine site flares or cutaneous immune related adverse events (irAEs) following ICI. Results: Of the 22 patients (11 male, 11 female) treated with adjuvant VT, median age at first vaccine was 53 years old. HLA type was known for 11 pts. Stage at initial VT was IIB to IIIC. 14 pts recurred following adjuvant VT. Median time from vaccine initiation to melanoma recurrence was 3.2 years (range 6.5 months to 11 years). 10 pts received ICI for recurrent melanoma, 3 pts received ipilimumab, 2 anti-PD1 monotherapy, 4 ipilimumab and nivolumab, and 1 nivolumab/relatlimab. Stage at first ICI was IIIB to IV M1d. 9 pts experienced cutaneous irAEs. 7 pts experienced local vaccine site flare reactions following ICI treatment. Additionally, 2 pts experienced vitiligo, 2 with dermatologic flares (bullous pemphigoid and psoriatic rash), 2 with generalized rash that resolved with steroid cream. 1 pt did not experience rash, vaccine site flare, nor irAE dermatologic flare. Of the pts who recurred, 2 pts had BRAF V600E mutations, and 1 of these pts experienced vaccine flare, the other did not. 1 pt with a BRAF Q16L mutation did not have vaccine flare. 6 out of 7 BRAF wild type pts who recurred and received ICI experienced a localized vaccine site flare. Median disease-free interval following ICI treatment was 1.5 years (range 3 months to 9 years). All 10 pts are disease-free and off ICI being closely monitored. Conclusions: Evidence of prior localized vaccination “flare” may be a biomarker for a complete immunologic response in pts with metastatic disease treated with immunotherapy. ICI targeting CTLA-4 and/or PD-1 both triggered this localized vaccination site response, suggesting that T cell memory and immunologic activation against melanoma antigens translate into clinical responses.
Mutation pattern of EGFR gene in Peruvian patients with non-small cell lung cancer.
Authors: Rossana Ruiz, Marco Galvez-Nino, Marco Santos, Franco Doimi, Luis Mas, Carolina Belmar-Lopez
Journal: Journal of Clinical Oncology (2024)

e20615 Background: The correct characterization of EGFR mutations is crucial to the proper management of NSCLC patients due to the possibility to treat these patients with specific targeted therapies. Herein we report the incidence, mutation pattern and novel mutations of EGFR mutation in Peruvian NSCLC patients. Methods: Between 2016 and 2023 a total of 1489 NSCLC patients from public and private centers were referred to ONCOGENOMICS laboratory for somatic mutation testing. Next Generation Sequencing (NGS) was performed using the Ampliseq for Illumina FOCUS or Custom panel and run on the Illumina MiSeq. Raw data were processed automatically on the BaseSpace Sequence Hub (Illumina) and aligned to the hg19 reference genome The default limit of detection (LOD) was set at 5% allelic frequency (VAF) in tissue samples and 0.5% VAF in cfDNA samples. Results: The study included 1401 NSCLC patients, 61.8% were women. Clinical stages were distributed III (22.5%), IV (77.5%). All tumors were adenocarcinoma. Incidence of EGFR-mutated NSCLC was 33.4% (450), 68.9% were women. We found 519 EGFR mutations in 450 tumors. Classical or common EGFR mutations; L858R or ex19del corresponded to 86.4% with 331 and 383 cases, respectively and L858R or ex19del + T790M corresponded to 13.6% with 2 cases onset and 50 cases in progression. EGFR T790M de novo mutations were found in 4 cases onset. In one case at diagnosis was detected a T790M-like 3R mutant EGFR p.(C797S); c.2390G &gt; C, a drug resistance point mutation in ex20.Non-classical or atypical EGFR mutations corresponded to 14.0% (63/450) of cases. Non-classical EGFR mutations were categorized as follows according to Janning et al.: (i) More frequent uncommon EGFR mutations - 39.7% (25/63) including G719X, S768I, E709X and L861Q (22/25); G719X + S768I (1/25); and combinations with classical EGFR mutation L858R + S768I (2/25). (ii) EGFR exon 20 insertions - 44.5% (28/63), including a novel mutation EGFR p.(769_770VDinsGFV);c.2308_2309ins. All were located in the loop following the C-helix. And (iii) very rare mutations - 15.9% (10/63) including very rare point mutations in ex19 (1/10), ex18del (4/10), ex19ins (1/10) and complex mutations (ex19del + very rare point mutation in ex19 (4/10).Two point mutation no reported previously were found, EGFR, ex19, p.(S752F);c.2255C &gt; T and EGFR, ex19, p.(T751P);c.2251A &gt; C, both as co-mutations with classical EGFR ex19del mutation. Conclusions: The present study underscores the value of NGS to optimally address EGFR mutations, specially the rare and novel ones due to its higher sensitivity and specificity compared to other techniques. This approach is particularly important for the Latin American population which is underrepresented in genomic databases. Clinical correlation of this genomic findings is ongoing.
Efficacy and safety of second-line immunotherapy in patients with advanced non-small cell lung cancer.
Authors: Laura Sánchez Escudero, Stephanie S. Cobelas Cartagena, María Sánchez Esperilla, Juan L. Bayo
Journal: Journal of Clinical Oncology (2024)

e20571 Background: Patients (Pts) with advanced non-small cell lung cancer (NSCLC) face limited treatment options. Immunotherapy (IO) has revolutionized the treatment of NSCLC in this setting. The objective of our study is to evaluate the efficacy and safety of atezolizumab (Az) in Pts with advanced NSCLC in the second-line setting following progression on platinum-based chemotherapy (CT) in the Huelva area. Additionally, we aim to compare the results with those obtained in the phase 2 POPLAR and phase 3 OAK clinical trials. Methods: This is a descriptive and observational study conducted on patients with advanced NSCLC who received second-line IO with atezolizumab 1200 mg/1680 mg every 3 or 4 weeks, from 2015 to 2023 in the Huelva area (Spain). SPSS Statistics 22 was used for data analysis. Results: 26 Pts were treated, median age 67 years and 88.5% men. ECOG PS 0-1 in 92.3%. According to smoking habits, 42.3% were ex-smokers and 38.5% were active smokers. Regarding histology, 53.8% were non-squamous. 73.1% were inicial stage IV and 23% were stage III. Depending on the expression of PDL-1, PDL-1 was &lt; 1% in 34.6% (9 Pts) of the sample, between 1-49% in 53.8% (14 Pt) and unknown in 3 Pts. 26.9% of patients achieved disease stability and 11.5% achieved partial response. The response has not been evaluated in 38.5% because these patients maintain treatment. The adverse effects (AE) suffered by patients treated with Az in the second line were 53.8% grade (G) 1- 2 and 7.7% G 3-4. The most frequent were asthenia (48%), pruritus and arthralgia in 15.4%, both cases, and skin toxicity in 11.5%. In the case of the 2 Pts with G 3-4 toxicity, they were due to autoimmune anemia and asthenia with subsequent to grade 1, so treatment did not have to be interrupted. The median progression-free survival (PFS) was 2.7 months (m) (95% CI 0-6.8) and the median overall survival (OS) was 5.2 m (95% CI 0.5- 9-9). In both cases the results were not statistically significant. According to PDL1, no statistically significant differences were found in the subgroup analysis. Conclusions: Based on our results and those of the Phase 2 POPLAR and Phase 3 OAK studies, we consider that Az has an acceptable safety profile, with fewer G 3-4 side effects compared to CT, so a lower percentage of Pts drop out the treatment. Although the PFS was similar to the phase II-III studies, the OS was lower, probably due to the percentage of Pts with rapid progression and patients currently continuing to receive treatment, being a limitation in our study along with the small sample size. Despite this, our results are encouraging regarding the benefit of IO in Pts. Therefore, we conclude that the use of IO in these Pts falls within good clinical practice, offering them a clearly effective therapy and thus avoiding treatments with greater toxicity such as CT.
Effects of lack of access to cancer medication on survival of patients with lung cancer.
Authors: Laura Nasser El-Halabi, Mohammad Hassan Mahmoud Hodroj, Firas Rammal, Ali Ghais, Rami Tfayli, Abdallah Bou Orm, Maya Charafeddine, Arafat H. Tfayli
Journal: Journal of Clinical Oncology (2024)

e20585 Background: Lung cancer is the leading cause of cancer-related death. The treatment has evolved with the introduction of immunotherapy. During the economic crisis in Lebanon, cancer medications became unavailable forcing oncologists to adjust treatment protocols. This study aims to assess the effect of medication shortage on the progression-free survival (PFS) of lung cancer patients treated at a tertiary care center in Lebanon. Methods: A retrospective analysis of patients with metastatic NSCLC treated during the period of drug shortage (October 2021-December 2022) as compared to those treated in 2019-2020. The primary end point was progression-free survival (PFS) on first line of therapy and its association with dose density ratio (dose density given/standard dose density). Electronic medical records of 117 patients were reviewed and data of 83 eligible patients were collected and analyzed using IBM SPSS software. Results: The mean age at diagnosis was 68 years. Of the total, 63.5% were male. Additionally, 14.4% of the patients received chemotherapy, 39.7% received immunotherapy, and 42.1% received a combination of chemotherapy and immunotherapy. In total, 49 patients were eligible in the 2019/2020 category. 84% of the patients had the opportunity to receive immunotherapy. In contrast, 25 patients were eligible in the 2021/2022 category, and only 73% of them had the opportunity to receive immunotherapy. The median PFS of the 2019/2020 category was 11.2 months, compared to 5.4 months in 2021-2022 (p-value of 0.339). PFS was studied based on the dose density ratio for immunotherapy. Twenty-two patients received a full immunotherapy dose with a ratio of 1, and their PFS was 5.43 months. Twelve patients received a dose density ratio ranging from 0.01 to 0.50 and had a PFS of 10 months. Twenty-nine patients received a dose density ratio of 0.51-0.99 and had PFS of 12.8 months. Contrary to our initial expectations, we did not observe a statistically significant difference between the dose density of immunotherapy and PFS values with a p-value of 0.107. Conclusions: Despite significant shortages in immunotherapy medications, our study suggests that this has no significant detrimental effect on PFS. This unexpected discovery challenges the conventional notion that full immunotherapy doses are necessary and prompts further exploration of the complex relationship between dosage and treatment outcomes in patients.