JTO Clinical and Research Reports最新文献

{"title":"Prognostic Value of KRAS/TP53 Status for Overall Survival in First-Line Monoimmunotherapy and Chemoimmunotherapy Treated Patients With Nonsquamous NSCLC in the Netherlands: A Brief Report","authors":"Vincent D. de Jager MD ,&nbsp;Léon C. van Kempen PhD ,&nbsp;Betzabel N. Cajiao Garcia MSc ,&nbsp;T. Jeroen N. Hiltermann MD, PhD ,&nbsp;Anthonie J. van der Wekken MD, PhD ,&nbsp;Ed Schuuring PhD ,&nbsp;Stefan M. Willems MD, PhD","doi":"10.1016/j.jtocrr.2024.100745","DOIUrl":"10.1016/j.jtocrr.2024.100745","url":null,"abstract":"<div><h3>Introduction</h3><div>Programmed death-ligand 1 (PD-L1) is the main predictive biomarker used to identify patients with NSCLC who are eligible for treatment with immune checkpoint inhibitors. Despite its utility, the predictive capacity of PD-L1 is limited, necessitating the exploration of supplementary predictive biomarkers. In this report, we describe the prognostic value of <em>KRAS</em>/<em>TP53</em> mutation status for overall survival (OS) in patients with NSCLC treated with first-line immunotherapy or combined chemoimmunotherapy.</div></div><div><h3>Methods</h3><div>Clinical data of all patients diagnosed with metastatic nonsquamous NSCLC in the Netherlands between January 1 and December 31 of 2019 were retrieved from the Netherlands Cancer Registry and linked to pathology reports of the Dutch Nationwide Pathology Databank. A total of 694 patients with available <em>KRAS</em> and <em>TP53</em> mutation status and treated with first-line pembrolizumab or chemoimmunotherapy were included, with a median follow-up time of 42.5 months. Patients with an <em>EGFR</em> or <em>MET</em> mutation or <em>ALK</em>, <em>ROS1,</em> or <em>RET</em> fusion were excluded from the analysis.</div></div><div><h3>Results</h3><div>Among patients treated with first-line pembrolizumab or chemoimmunotherapy, mutations in <em>KRAS</em> and <em>TP53</em> occurred in 48.8% (n = 339) and 58.4% (n = 405), respectively. OS differed significantly between <em>KRAS</em>/<em>TP53</em> mutational subgroups in patients treated with first-line pembrolizumab or chemoimmunotherapy (log-rank test, <em>p</em> = 0.007). Median OS of pembrolizumab or chemoimmunotherapy treated patients with mutated <em>TP53</em> was longer in patients with <em>KRAS</em>-wildtype (485 versus 359 d, hazard ratio [HR] = 0.76, <em>p</em> = 0.028) or mutated <em>KRAS</em> (571 versus 447 d, HR = 0.73, <em>p</em> = 0.019). In a separate analysis of treatment subgroups, mutated <em>TP53</em> was associated with longer median OS in chemoimmunotherapy treated <em>KRAS</em>-wildtype patients (468 versus 341 d, HR = 0.71, <em>p</em> = 0.029) but not in monoimmunotherapy treated patients with <em>KRAS</em>-wildtype (512 versus 371 d, HR = 0.91, <em>p</em> = 0.78). In multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, <em>KRAS</em>/<em>TP53</em> mutation status was no longer associated with OS.</div></div><div><h3>Conclusions</h3><div>Among patients with metastatic NSCLC who are treated with pembrolizumab or chemoimmunotherapy, the presence of a pathogenic <em>TP53</em> and <em>KRAS</em> mutation is associated with longer OS. Nevertheless, in multivariable Cox regression analysis including age, sex, clinical disease stage, and PD-L1 tumor proportion score, <em>KRAS</em>/<em>TP53</em> mutation status was no longer associated with OS.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100745"},"PeriodicalIF":3.0,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcomes of Maintenance Durvalumab After Definitive Concurrent Chemoradiotherapy in Unresectable Locally Advanced Stage III NSCLC According to EGFR and ALK Status: Korean Cancer Study Group LU-22-18","authors":"Dae-Ho Choi MD ,&nbsp;Miso Kim MD, PhD ,&nbsp;Young Saing Kim MD, PhD ,&nbsp;Keon Uk Park MD, PhD ,&nbsp;Jang Ho Cho MD, PhD ,&nbsp;Hongsik Kim MD, PhD ,&nbsp;Ki Hyeong Lee MD, PhD ,&nbsp;Heejoon Ahn MD, PhD ,&nbsp;Il-Hwan Kim MD, PhD ,&nbsp;Kyung-Hee Lee MD, PhD ,&nbsp;Gyeong-Won Lee MD, PhD ,&nbsp;Seong Yoon Yi MD, PhD ,&nbsp;Beung chul Ahn MD, PhD ,&nbsp;Min-Young Lee MD, PhD ,&nbsp;Hyun Ae Jung MD, PhD ,&nbsp;Sehhoon Park MD, PhD ,&nbsp;Jong-Mu Sun MD, PhD ,&nbsp;Jin Seok Ahn MD, PhD ,&nbsp;Se-Hoon Lee MD, PhD ,&nbsp;Myung-Ju Ahn MD, PhD","doi":"10.1016/j.jtocrr.2024.100734","DOIUrl":"10.1016/j.jtocrr.2024.100734","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of maintenance durvalumab after definitive concurrent chemoradiotherapy (CCRT) in unresectable locally advanced NSCLC with <em>EGFR</em> mutation or <em>ALK</em> translocation remains unclear. We compared the effectiveness of durvalumab maintenance therapy in groups with <em>EGFR</em> and <em>ALK</em> wild-type versus those with <em>EGFR</em> or <em>ALK</em> mutations.</div></div><div><h3>Methods</h3><div>In this retrospective multicenter observational study, patients with locally advanced NSCLC without progression after CCRT followed by maintenance durvalumab and available molecular test results (<em>EGFR</em> and <em>ALK</em>) were eligible. The primary objective was to compare progression-free survival (PFS) between <em>EGFR</em> and <em>ALK</em> wild-type and <em>EGFR</em> or <em>ALK</em> mutant NSCLC. Secondary objectives include overall survival according to <em>EGFR</em> or <em>ALK</em> mutation and programmed death-ligand 1 (PD-L1) expression.</div></div><div><h3>Results</h3><div>Among 339 patients, 279 had wild-type <em>EGFR/ALK</em>, 41 had <em>EGFR</em> mutations and 19 had <em>ALK</em> translocations. The median age was 68 years with 276 male individuals (81.4%) and 63 female individuals (18.6%), 165 (49.3%) had adenocarcinoma, 149 (44.5%) had squamous cell carcinoma, and 21 (6.3%) had other histologic types, 120 (35.4%) had stage IIIA, 168 (49.6%) stage IIIB, and 51 (15.0%) had stage IIIC. Most of the patients (n = 288, 85%) achieved partial response to CCRT, two (0.6%) had a complete response, and 49 patients (14.4%) had stable disease. Excluding four patients with unknown PD-L1 tumor proportion score (TPS), 16 (4.8%) had a PD-L1 TPS of 0, 168 (50.1%) had 1 to 49, and 151 (45.1%) had 50 or higher. The median PFS was 21.4 months (95% confidence interval [CI]: 17.3–25.3) for the EGFR/ALK wild-type group and 21.0 months (95% CI: 15.7–not available [NA]) for the <em>EGFR</em> or <em>ALK</em> mutant group with no difference (<em>p =</em> 0.74). Significant differences occurred in PFS on the basis of PD-L1 expression with values of 13.6 (95% CI: 10.5–NA), 18.7 (95% CI: 15.1–26.9), and 24.7 (95% CI: 20.7–NA) months for TPS of 0, 1–49, and 50 or higher, respectively (<em>p =</em> 0.02).</div></div><div><h3>Conclusions</h3><div>Durvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with <em>EGFR</em> or <em>ALK</em> mutation demonstrates comparable clinical outcomes to those with wild-type <em>EGFR/ALK</em> when PD-L1 expression is present.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100734"},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Reply to Craig et al.","authors":"Nicola Hill MB, BCh, BAO, FRCR,&nbsp;Gerard G. Hanna FRCR, PhD,&nbsp;Gerard M. Walls FRCR, PhD,&nbsp;Jonathan McAleese FRCR","doi":"10.1016/j.jtocrr.2024.100739","DOIUrl":"10.1016/j.jtocrr.2024.100739","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100739"},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S1701, A Randomized Phase 2 Trial of Carboplatin-Paclitaxel With and Without Ramucirumab in Patients With Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma","authors":"Anne S. Tsao MD, MBA ,&nbsp;Ming-Hui Hsieh MS ,&nbsp;Marianna Koczywas MD ,&nbsp;Janet Tu MD ,&nbsp;Jonathan Riess MD, MS ,&nbsp;Tawee Tanvetyanon MD ,&nbsp;Barbara T. Ma MD ,&nbsp;Ying-Qi Zhao PhD ,&nbsp;Mary W. Redman PhD ,&nbsp;Martin J. Edelman MD ,&nbsp;David R. Gandara MD ,&nbsp;Jhanelle E. Gray MD ,&nbsp;Karen L. Kelly MD","doi":"10.1016/j.jtocrr.2024.100738","DOIUrl":"10.1016/j.jtocrr.2024.100738","url":null,"abstract":"<div><h3>Introduction</h3><div>Thymic carcinoma is a rare and aggressive malignancy with few treatment options. Preclinical studies suggested that targeting the angiogenic pathway may be beneficial in this disease.</div></div><div><h3>Methods</h3><div>This randomized phase 2 trial enrolled patients with unresectable, locally advanced, recurrent, or metastatic thymic carcinoma. Patients were randomized to receive carboplatin-paclitaxel with or without ramucirumab. The primary end point was progression-free survival (PFS) and secondary end points included response by Response Evaluation Criteria in Solid Tumors, disease control, toxicity, and overall survival. The primary analysis was done using a one-sided 10%-level log-rank test. Target sample size was 66 patients.</div></div><div><h3>Results</h3><div>Between 2018 and 2022, 21 patients enrolled to ramucirumab plus carboplatin-paclitaxel (RCP, n = 8) and to the control arm (carboplatin-paclitaxel [CP], n = 13) with one patient on CP not meeting eligibility criteria. Owing to slow accrual, the study was terminated early by the Data and Safety Monitoring Board. Of the 20 eligible patients, eight on RCP and nine on CP received protocol treatment. PFS was not statistically different (hazard ratio = 0.51, 80% confidence interval [CI]: 0.24–1.09, <em>p</em> = 0.13). There were no grade 4 or higher treatment-related adverse events with RCP, although 50% experienced grade 3 adverse events, in which one patient had a grade 3 thromboembolic event. Among nine assessable patients for toxicity on CP, one patient (11%) encountered grade 4 neutropenia and one patient (11%) reported grade 3 thromboembolic events. Response rates favored the RCP arm, with an 88% (seven of eight, 80% CI: 59%–99%) response rate compared with 40% (four of 10, 80% CI: 19%–65%) on CP arm (<em>p</em> = 0.04). Disease control rate was higher in the RCP arm (100% versus 70%, <em>p</em> = 0.09). At the time of analysis, as only one death has been reported, overall survival remains immature.</div></div><div><h3>Conclusions</h3><div>Accrual to this population is challenging, and the study was closed early because of feasibility. Although PFS was not statistically better with RCP, the hazard ratio was 0.51 and the lack of significance was likely due to small sample sizes. Notably, addition of ramucirumab to CP led to higher response rates than CP alone. Future research should consider exploring larger multicenter trials and other combinations to improve outcomes. Challenges in enrollment emphasize the need for innovative strategies and larger collaborations in rare malignancies such as thymic carcinoma.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100738"},"PeriodicalIF":3.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment","authors":"Sabine Schmid MD ,&nbsp;Lisa Holer MSc ,&nbsp;Katrin Gysel MSc ,&nbsp;Kira-Lee Koster MD ,&nbsp;Sacha I. Rothschild MD ,&nbsp;Laura A. Boos MD ,&nbsp;Lorenz Frehner MD ,&nbsp;Sabine Cardoso Almeida MD ,&nbsp;Christian Britschgi MD, PhD ,&nbsp;Yannis Metaxas MD ,&nbsp;Michael Mark MD ,&nbsp;Patrizia Froesch MD ,&nbsp;Wolf-Dieter Janthur MD ,&nbsp;Anna Allemann MD ,&nbsp;Christine Waibel MD ,&nbsp;Catherine Von der Mühll-Schill MD ,&nbsp;Martin Früh MD ,&nbsp;Laetitia A. Mauti MD, PhD","doi":"10.1016/j.jtocrr.2024.100735","DOIUrl":"10.1016/j.jtocrr.2024.100735","url":null,"abstract":"<div><h3>Objectives</h3><div>On the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi-nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi-nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi-nivo for patients with MPM in Switzerland.</div></div><div><h3>Methods</h3><div>Twelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators.</div></div><div><h3>Results</h3><div>Of the 109 patients with MPM treated with ipi-nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi-nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, <em>p</em> &lt; 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi-nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients.</div></div><div><h3>Conclusion</h3><div>In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100735"},"PeriodicalIF":3.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRYOVATE: A Pilot Study of Lung Cancer Cryoactivation in Combination With Immunotherapy in Advanced NSCLC","authors":"Antoine Desilets MD, MSc ,&nbsp;Gabryella Pinheiro PhD ,&nbsp;Wiam Belkaid PhD ,&nbsp;Olivier Salko MD ,&nbsp;Julie Malo ,&nbsp;Eleyine Zarour MD ,&nbsp;Adeline Jouquan MSc ,&nbsp;Anne-Julie Thibaudeau MSc ,&nbsp;Marc-Antoine Nolin MSc ,&nbsp;John Stagg PhD ,&nbsp;Marie Florescu MD ,&nbsp;Mustapha Tehfe MD ,&nbsp;Normand Blais MD, MSc ,&nbsp;Samer Tabchi MD ,&nbsp;Jean Chalaoui MD ,&nbsp;Philippe Stephenson MD ,&nbsp;Arielle Elkrief MD ,&nbsp;Vincent Quoc-Huy Trinh MD, MSc ,&nbsp;Bertrand Routy MD, PhD ,&nbsp;Moishe Liberman MD, PhD","doi":"10.1016/j.jtocrr.2024.100737","DOIUrl":"10.1016/j.jtocrr.2024.100737","url":null,"abstract":"<div><h3>Introduction</h3><div>NSCLC is the leading cause of cancer-related mortality. Although immune-checkpoint inhibitors (ICIs) have improved survival in patients with advanced NSCLC, treatment resistance remains a challenge. Cryoactivation, a technique inducing cell death by cycles of freezing and thawing, has the potential to augment tumor responses when combined with ICIs.</div></div><div><h3>Methods</h3><div>This single-arm phase 1 clinical trial enrolled patients with previously untreated advanced NSCLC and 50% or higher programmed cell death ligand-1 (PD-L1). Patients underwent cryoactivation followed by ICI monotherapy initiated 5 days later. The primary end point was the objective response rate. Co-secondary end points included the safety and feasibility of the procedure and overall survival. Immune cell infiltration by immunohistochemistry was performed on paired pre- and post-treatment samples, with patients dichotomized according to clinical benefit (CB) rate (CB versus no CB [NCB]).</div></div><div><h3>Results</h3><div>Eight patients were enrolled. Two patients achieved a partial response, yielding an objective response rate of 25%. Median progression-free survival and overall survival were 3.8 and 13.0 months, respectively. The cryoactivation procedure was well tolerated, without grade 3 to 4 adverse events. Post-hoc analysis reported a CB rate of 50%. Immunohistochemistry analysis reported a numerical difference in the cluster of differentiation 8–positive (CD8⁺) T cell infiltration in CB versus NCB in the pre- and post-treatment biopsies (<em>p</em> = 0.09) and an increase in CD8⁺ T cells in the post-treatment biopsies of CB versus NCB (<em>p</em> = 0.03).</div></div><div><h3>Conclusions</h3><div>Although cryoactivation combined with pembrolizumab was safe and well tolerated in patients with NSCLC, therapeutic benefits were not evident compared with historical cohorts of ICI monotherapy. Correlative analyses validated CD8⁺ T cell recruitment in patients deriving CB.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100737"},"PeriodicalIF":3.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study","authors":"Lauren Julia Brown M.B.B.S., MClinTRes, FRACP ,&nbsp;Julie Ahn M.B.B.S. ,&nbsp;Bo Gao BMedSci M.B.B.S., FRACP, PhD ,&nbsp;Harriet Gee M.B.B.S., DPhil, FRANZCR ,&nbsp;Adnan Nagrial M.B.B.S., FRACP, PhD ,&nbsp;Inês Pires da Silva MD, FRACP, PhD ,&nbsp;Eric Hau BSc (Med), M.B.B.S., Grad Cert (Biostat), FRANZCR, PhD","doi":"10.1016/j.jtocrr.2024.100695","DOIUrl":"10.1016/j.jtocrr.2024.100695","url":null,"abstract":"<div><h3>Introduction</h3><div>The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers. We sought to characterize the frequency and location of oligoprogression and determine the overall survival (OS) after radiotherapy in this population.</div></div><div><h3>Results</h3><div>A total of 159 patients were included in the study. At first progression, 62 (39.0%) were classified as undergoing oligoprogression. Multivariate analysis confirmed the presence of brain metastases was associated with an increased likelihood of oligoprogression (OR = 2.44, <em>p</em> = 0.04) with most (63.2%) of these patients experiencing progression intracranially. The presence of liver metastases was associated with a decreased likelihood of oligoprogression (OR = 0.17, <em>p &lt;</em> 0.01). For patients with oligoprogression, those who received radiotherapy had a longer median progression-free survival-2 (PFS2) (17 versus 11.5 mo, HR = 0.51, <em>p</em> = 0.02) and a longer median OS (23 versus 13 mo, HR = 0.40, <em>p &lt;</em> 0.001) compared with those who did not receive radiotherapy. No difference in PFS2 or OS outcomes was observed between patients who received radiotherapy versus those who did not for systemic progression.</div></div><div><h3>Conclusions</h3><div>In patients with oligoprogressive metastatic NSCLC after treatment with first-line ICIs, radiotherapy significantly improves OS and PFS2 outcomes. Patients with baseline brain metastases are more likely to experience oligoprogression. Further prospective studies in directed, less heterogeneous populations of patients with metastatic NSCLC will be fundamental to optimize management.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 10","pages":"Article 100695"},"PeriodicalIF":3.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracranial Response to Selpercatinib After Pralsetinib-Induced Disease Progression in Rearranged During Transfection Fusion-Positive Non-Small-Cell Lung Cancer: Case Report","authors":"Illaa Smesseim MD,&nbsp;Tijmen van der Wel MD,&nbsp;Sushil K. Badrising MD, PhD","doi":"10.1016/j.jtocrr.2024.100730","DOIUrl":"10.1016/j.jtocrr.2024.100730","url":null,"abstract":"<div><div>RET fusion-positive NSCLC accounts for 1% to 2% of lung carcinoma cases. Although two Food and Drug Administration–approved selective RET inhibitors, pralsetinib, and selpercatinib, have revealed efficacy in managing RET fusion-positive NSCLC, this case series is unique in its focus on the intracranial response to selpercatinib after disease progression during pralsetinib treatment. This report contributes to the literature by providing evidence of selpercatinib’s potential as a treatment option in such refractory cases. The patients described in both cases were diagnosed with metastatic RET fusion-positive NSCLC and developed intracranial metastases during pralsetinib treatment. After switching to selpercatinib, both exhibited significant intracranial responses. The first patient reported a reduction in brain metastasis size and maintained a response for over 1.5 years. The second patient also responded intracranially to selpercatinib but unfortunately passed away 8 months later owing to pulmonary hemorrhage, possibly linked to prior radiation treatment. These cases highlight the potential efficacy of selpercatinib in treating intracranial metastases in RET fusion-positive patients with NSCLC after pralsetinib-refractory progression. The key takeaway is that selpercatinib may offer a viable treatment option in such scenarios, although more extensive studies are needed to determine its role as a monotherapy or in combination with other treatments.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100730"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developing a Conceptual Framework for a Person-Centered Approach to Improving Adherence and Outcomes in Lung Cancer Screening: The Engaged Approach to Lung Cancer Screening: A Brief Report","authors":"Margaret M. Byrne PhD ,&nbsp;Erin A. Hirsch PhD, MS ,&nbsp;Kaitlyn Hoover MS ,&nbsp;Jessica H. McCoy RN, BSN ,&nbsp;Courtney R. Blair MS ,&nbsp;Michelle Futrell RN ,&nbsp;Upal Basu Roy PhD, MPH ,&nbsp;Jamie L. Studts PhD","doi":"10.1016/j.jtocrr.2024.100728","DOIUrl":"10.1016/j.jtocrr.2024.100728","url":null,"abstract":"<div><h3>Introduction</h3><div>Translating outcomes from randomized trials of lung cancer screening into community practice settings has been challenging. We developed a framework—the Engaged Approach to Lung Cancer Screening (EA-LCS)—for improving adherence and individual and population health outcomes in LCS.</div></div><div><h3>Methods</h3><div>Employing community-engaged research, we conducted semistructured interviews with LCS program staff (N = 15) and participants (N = 7) and administered brief surveys to understand LCS adherence. We combined our knowledge of LCS implementation with data to formulate the EA-LCS framework<em>,</em> including principles and strategies instrumental for LCS adherence.</div></div><div><h3>Results</h3><div>Program staff identified four factors that facilitated adherence: (1) the use of specialized tracking software, (2) the importance of personal connection and a reliable touchpoint, (3) centralized program operations, and (4) standardization and streamlining of reports to participants and clinicians. Participant data identified four factors supporting adherence: (1) a single contact point and information availability, (2) tailored communications, (3) personalized results delivery, and (4) increased scan accessibility. Combined analyses identified three overarching themes in the EA-LCS framework: (1) respect, (2) trust, and (3) engagement.</div></div><div><h3>Conclusions</h3><div>The EA-LCS conceptual model integrates three foundational principles (person-centeredness, trustworthy relationships, and sustained communications) to enhance LCS adherence. Efforts are underway to translate the EA-LCS framework into materials to support adherence.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100728"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC","authors":"Lianxi Song MD ,&nbsp;Huan Yan MD ,&nbsp;Qinqin Xu MD ,&nbsp;Chunhua Zhou MD ,&nbsp;Juan Liang MD ,&nbsp;Shaoding Lin MD ,&nbsp;Ruiguang Zhang MD ,&nbsp;Juan Yu MD ,&nbsp;Yang Xia MD ,&nbsp;Nong Yang MD ,&nbsp;Liang Zeng MD ,&nbsp;Yongchang Zhang MD","doi":"10.1016/j.jtocrr.2024.100729","DOIUrl":"10.1016/j.jtocrr.2024.100729","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset.</div></div><div><h3>Methods</h3><div>We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76).</div></div><div><h3>Results</h3><div>The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (<em>p</em> &gt; 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant <em>ALK</em> fusion than those with echinoderm microtubule-associated protein-like 4<em>–ALK</em> variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%.</div></div><div><h3>Conclusions</h3><div>Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100729"},"PeriodicalIF":3.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}