bluuebunny/crossref_metadata_2025_split huggingface dataset:
Once weekly selinexor, carfilzomib, and dexamethasone (SKd) in patients with relapsed/refractory multiple myeloma (MM).
Authors: Gasparetto Cristina , Lipe Brea , Tuchman Sascha , Callander Natalie Scott , Lentzsch Suzanne , Baljevic Muhamed , Rossi Adriana C. , Bahlis Nizar J. , White Darell , Chen Christine , Sutherland Heather J , Kotb Rami , LeBlanc Richard , Sebag Michael , Venner Christopher P , Bensinger William , Sheehan Heidi , Ju Yawen , Kai Kazuharu , Schiller Gary J. 
Published: May 2020

8530 Background: Selinexor is a novel, first-in-class selective inhibitor of nuclear export (SINE), which blocks exportin 1 (XPO1), forcing the nuclear retention and activation of tumor suppressor proteins. Selinexor in combination with low dose dexamethasone (Sel-dex) was approved by the FDA, based on data from the STORM study wherein Sel-dex induced an overall response rate (ORR) of 26.2% in patients (pts) with refractory MM. We hypothesize that once weekly (QW) SKd may be an active well tolerated regimen and evaluated this combination in a dose escalation/expansion study. Methods: STOMP is a phase 1b/2 study evaluating various doses and enrolled pts with carfilzomib naive relapsed MM. Oral selinexor was dosed QW at 80 or 100 mg. Carfilzomib was dosed QW (on days 1, 8 and 15 of 28-day cycle) at 56 mg/m2 or 70 mg/m2. Dexamethasone was dosed at 40 mg QW. The primary objectives of the study are to assess the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), as well as explore the efficacy and safety of SKd. Results: As of January 2020, 18 pts were enrolled. Median age was 71 years (range: 50-76). Median number of prior regimens was 4 (range: 1-8). All pts (n = 18) were previously treated with bortezomib and lenalidomide, and 50% and 56% pts were refractory to bortezomib and lenalidomide respectively. Nine (50%) pts received prior pomalidomide treatment and 8 (44%) pts were refractory. Eleven (61%) pts received prior daratumumab treatment and 9 (50%) were refractory. The MTD was selinexor 80 mg QW, carfilzomib 56 mg/m2 QW and dexamethasone 40 mg QW. The ORR and CBR were 72% and 79% respectively with 4 complete responses, 7 very good partial responses, 2 partial responses, and 1 minimal response. Stable disease was observed in 3 pts. With a median follow-up period of 4.7 (1.8-16.3) months, median progression-free survival has not been reached. Common treatment-related adverse events (total, Grade ≥3) were thrombocytopenia (83.3%, 66.7%), nausea (66.7%, 0%), anemia (55.6%, 11.1%), fatigue (50%, 11.1%), anorexia (44%, 5.6%), weight loss (44%, 0%), and neutropenia (33.3%, 11.1%). Conclusions: Once weekly SKd demonstrated an encouraging ORR of 72% in pts with a median of 4 lines of prior therapy. The majority of responses are deep and predominantly CR and VGPR. The combination is well tolerated with no new safety signal, no Grade ≥3 nausea, vomiting, diarrhea, weight loss or anorexia. The side effects are a function of the dose and schedule and can be managed with dose modification and supportive care. Enrolment is ongoing and supports a phase 3 study of SKd. Clinical trial information: NCT02343042 .
Oncolytic virus pelareorep plus carfilzomib phase I trial in carfilzomib-refractory patients (NCI 9603): Responses with cytokine storm.
Authors: Sborov Douglas Weston , Viola Domenico , Dona Ada A , Nooka Ajay K. , Kaufman Jonathan L. , Lonial Sagar , Boise Lawrence , Dhodapkar Madhav V. , Joseph Nisha , Pichiorri Flavia , Hofmeister Craig C. 
Published: May 2020

8535 Background: Viral oncolytic therapy with intravenous Pelareorep, the infusible form of reovirus, is supported by preclinical data indicating that its antitumor activity results from direct cytolysis and an immune response against infected MM cells. Our preclinical data has shown that monocytes serve as carriers of reovirus from the peripheral blood to the bone marrow (Dona et al, ASH, 2019). In this abstract we present patients treated to date that were Carfilzomib refractory at enrollment. Methods: Pelareorep (P), Carfilzomib (K), and dexamethasone (d) were all infused on days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Patients were pretreated with dexamethasone 20 mg intravenously, then Carfilzomib 20 mg/m2 on days 1 and 2 of cycle 1, and 56 mg/m2 thereafter. Pelareorep dose levels were at 3x1010, 4.5*1010, and planned 9*1010 median tissue culture infectious dose (TCID50). Results: All 6 evaluable patients showed reovirus infection in the post-treatment marrow aspirates cycle 1 day 9. Despite all patients having Carfilzomib-refractory disease, 2 patients achieved partial responses, two patients with short duration stable disease but few side effects, and 2 patients with PD. Of the two responders, one patient developed fever and grade 4 thrombocytopenia during cycle 1 and withdrew mid cycle. The other patient with a PR developed a cytokine storm - this patient presented cycle 1 day 3 hypoxemic with pneumonia, systolic failure (LVEF 69%-- > 26%), with biochemical evidence of hemophagocytic syndrome with elevated IL-2R, IL-6, and ferritin > 25K. This patient responded to tocilizumab, but ultimately died two weeks later with sepsis. Autopsy revealed pneumonia, no areas of reovirus infection other than in myeloma cells, and reovirus productive infection in 5-35% of myeloma cells (i.e. capsid protein). Conclusions: While infection of myeloma cells was seen in all evaluable patients on cycle 1 day 9, those with a clinical response demonstrated concomitant CD8 & NK cell recruitment, PD L1 upregulation, activated caspase-3 expression, increased viral protein production within the myeloma cells, and these patients demonstrated mild to severe signs and symptoms consistent with secondary HLH. This is the first report of cytokine storm after oncolytic virus in a patient with a blood cancer, a syndrome thought to be related to T-cell activation from the combination treatment. This trial was supported by the NCI Division of Cancer Treatment & Diagnosis Cancer Therapy Evaluation Program (CTEP). Clinical trial information: NCT02101944 .
FDA analysis: Impact of BMI on efficacy outcomes in multiple myeloma trials.
Authors: Ershler Rachel , Fernandes Laura L , Kanapuru Bindu , Gwise Thomas , Kluetz Paul Gustav , Theoret Marc Robert , Gormley Nicole , Pazdur Richard 
Published: May 2020

8543 Background: Obesity has been implicated as a risk factor for the development of certain types of cancers, including multiple myeloma. Previous studies in other tumor types suggest that overweight subjects may have better outcomes, however, in relapsed/refractory multiple myeloma (RRMM), it is unknown whether body weight affects outcomes to therapy. Methods: We conducted a retrospective analysis of 13 RRMM clinical trials submitted to the FDA between 2012-2018. Patients were divided into four groups, underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5- < 25 kg/m2), overweight (BMI 25.0- < 30 kg/m2) and obese (BMI > 30.0 kg/m2). A multivariate analysis for progression free survival (PFS) and overall survival (OS), stratified by study and adjusted for age, cytogenetic risk group (Standard, High, Unknown), immunoglobin subtype (IgG Y/N), ECOG status (0-1, > 1, UNK), sex (M/F) was used to estimate the HR. Results: A total of 5898 patients were included in this analysis. The median age was 65 years (range 30-91 years). A total of 87(1.5%) patients were underweight, 1853 (31%) were normal weight, 2212 (38%) were overweight, 1332 (23%) were obese, and 414 (7%) had missing BMI. The results of the multivariate analysis of PFS and OS are shown in the Table. Conclusions: Exploratory analysis of patients with RRMM found that patients who were overweight and obese had a trend towards slightly improved PFS and OS when compared to normal weight patients. Similar trends were observed in the analyses of overall response rate and BMI (not presented in the abstract). These results are consistent with previous studies in other malignancies. Limitations include the lack of adjustment for multiple testing, the small sample of patients in the underweight category, and heterogeneity in the treatment regimens and PFS assessments in the clinical trials included in the analysis. Future studies are needed to evaluate safety and impact of treatment regimens on efficacy outcome measures based on body weight. [Table: see text]
Sporadic late-onset nemaline myopathy with monoclonal paraprotein as a malignancy rather than disimmunity and treatment with chemotherapy-based approach.
Authors: Kotchetkov Rouslan , Susman David , Buadi Francis , Dispenzieri Angela 
Published: May 2020

8545 Background: A subset of sporadic late-onset nemaline myopathy (SLONM) associated with monoclonal gammopathy of undetermined significance (MGUS) has more aggressive course, often fatal. Whether SLONM+MGUS is a malignancy or dysimmunity is unclear. Two approaches are used to treat SLONM+MGUS: 1) immunosuppression (IS) ± plasmapheresis/exchange; 2) chemotherapy (ChT) ± autologous stem cell transplantation (ASCT). Due to the rare occurrence of the disease the best treatment modality is not known. Methods: We conducted a literature search to identify previous treatment for patients with SLONM+MGUS using PubMed, Elsevier, Medline, and CINAHL databases from 1975 to 2019. All publications were carefully reviewed to remove “duplicate” patients. Overall, 28 reports were included for the final analysis. Results: 38 unique patients with SLONM+MGUS received either IS (n = 19) or ChT ± ASCT (n = 19). The median age was 48 years [24-75]. In the IT group 74% (n = 14) were males vs 53% (n = 10) in the ChT group. All patients had IgG monoclonal protein (MP): kappa in 57% (n = 11) in the IT, 42% (n = 8) in the ChT group. In the IT group MP values were 0.42 & 0.2 g/L (n = 2); in the ChT group median MP was 2.7 g/L [0.1-14, n = 14]. In the IT group 84% (n = 16) received steroids, 26% (n = 5) plasmapheresis, 53% (n = 10) non-steroid immunosuppressants, 11% (n = 2) rituximab, and 53% (n = 10) IVIG. Six patients (32%) had one IT modality; 13 (68%) had 2 or 3. In the ChT group 10 patients (53%) had ASCT; 6 patients (31%) had CyBorD or Lenalidomide+Dexamethasone + ASCT; 3 patients (16%) had chemotherapy without ASCT. 10 patients in IT group had neurological improvement (NI): 53% overall response (OR) with 16% (n = 3) complete remission (CR), and 37% (n = 7) partial response (PR). No improvement/progression had 9 patients (47%). In 2 patients (10%), neurological CR was associated with resolution of MP. Mean time to best response was 19 months. In ChT group 18 patients achieved NI: 94.7% OR with CR in 73.7% (n = 14) and PR in 21.0% (n = 4). Only one patient had no response to therapy. The best NI correlated with resolution of MP. Mean time to best response was 10 months. Conclusions: Our study with the most extensive cohort of patients with SLOMN+MGUS supports ChT ± consolidative ASCT aimed at complete elimination of the malignant plasma cell clone as the preferred treatment. Superior clinical benefits of ChT suggest that the presence of MP has clinical rather than undetermined significance, and SLOAN + MP should be considered as a malignancy rather than dysimmunity.
Phase II study of pembrolizumab (pembro) plus platinum doublet chemotherapy and radiotherapy as first-line therapy for unresectable, locally advanced stage III NSCLC: KEYNOTE-799.
Authors: Jabbour Salma K. , Lee Ki Hyeong , Frost Nicolaj , Kowalski Dariusz , Breder Valeriy Vladimirovich , Pollock Theodore , Reguart Noemi , Houghton Baerin , Quantin Xavier , Keller Steven M. , Liu Hong , Piperdi Bilal , Reck Martin 
Published: May 2020

9008 Background: KEYNOTE-799 (NCT03631784) evaluates pembro plus concurrent chemoradiation therapy (CCRT) in pts with unresectable, locally advanced stage III NSCLC. Methods: In this phase 2, nonrandomized, open-label trial, pts with previously untreated, unresectable, pathologically confirmed stage IIIA–C NSCLC with measurable disease (RECIST 1.1) received up to 17 cycles of pembro 200 mg Q3W starting with cycle 1 plus standard thoracic radiotherapy (60 Gy in 30 daily 2-Gy fractions) in cycles 2–3 and investigator’s choice of paclitaxel 200 mg/m2 + carboplatin AUC 6 Q3W for cycle 1, then paclitaxel 45 mg/m2 + carboplatin AUC 2 QW for cycles 2–3 (cohort A), or cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 Q3W (nonsquamous only) in cycles 1–3 (cohort B). Primary endpoints were ORR (CR/PR per RECIST 1.1 by blinded independent central review) and rate of grade ≥3 pneumonitis (per NCI CTCAE v4.0). CIs were estimated using the Clopper-Pearson method. Safety was assessed in all treated patients; efficacy was assessed in pts with ≥15 wks follow-up. Results: As of Jan 3, 2020, 112 and 73 pts have been enrolled in cohorts A and B, respectively; 63 in cohort A and 52 in cohort B continue on treatment. Median (range) follow up was 8.3 (0.7–14.0) mo in cohort A and 5.8 (0.2–13.7) mo in cohort B. ORR (90% CI) was 67.0% (58.9%–74.3%) in cohort A and 56.6% (44.4%–68.2%) in cohort B (Table). Grade ≥3 pneumonitis occurred in 9 pts (8.0%; 90% CI, 4.3%–13.6%) in cohort A and 4 pts (5.5%; 90% CI, 1.9%–12.1%) in cohort B. Treatment-related grade ≥3 AEs occurred in 72 pts (64.3%) in cohort A and 30 pts (41.1%) in cohort B. 4 pts had treatment-related grade 5 pneumonitis (all in cohort A). Enrollment is complete for cohort A and ongoing in cohort B. Conclusions: Pembro plus CCRT shows promising antitumor activity in pts with unresectable, locally advanced stage III NSCLC. Toxicity was as anticipated with pembro plus CCRT. Clinical trial information: NCT03631784. [Table: see text]
Molecular subtypes and clinical outcomes to initial systemic treatment in patients with small cell lung cancer.
Authors: Lai Wei-Chu Victoria , Egger Jacklynn V. , Rizvi Hira , Richards Allison L. , Beras Amanda , Baine Marina K. , Hsieh Min-Shu , Chang Jason C. , Rekhtman Natasha , Plodkowski Andrew J. , Ginsberg Michelle S. , Kris Mark G. , Hellmann Matthew David , Sen Triparna , Poirier John T. , Rudin Charles M. 
Published: May 2020

9018 Background: Investigators have proposed that differential expression of the transcription regulators ASCL1 and NeuroD1 can be used to define molecular subtypes of small cell lung cancers (SCLCs). Here we evaluate SCLC subtypes based on ASCL1 and NeuroD1 expression in patients (pts) treated with first-line (1L) chemotherapy profiled with targeted next-generation sequencing (NGS). Methods: We used NGS (MSK-IMPACT) to profile tumors from pts with SCLCs. We performed IHC to assess ASCL1 (A) or NeuroD1 (N). Objective response rate (ORR) to therapy was determined using RECIST. PFS and OS were analyzed using Kaplan-Meier. Results: 281 pts with SCLCs were profiled with NGS (102 LS-SCLC; 179 ES-SCLC). Most frequently mutated genes were TP53 (90%), RB1 (68%), KMT2D (22%), NOTCH1 (15%), FAT1 (14%), PTPRD (12%). Mutations in BIRC3, FOXL2, TENT5C, TET1, NRAS, KIT, TSHR, ESR1 were enriched in ASCL1-/NeuroD1+ (A-/N+), and mutations in KMT2D and EP300 were enriched in A-/N- (p<0.05). Copy number alterations in WWTR1, ATR, IKZF1, PALB2, PIK3CB were enriched in A-/N+ (p<0.05). IHC for ASCL1 and NeuroD1 was performed on 78 samples: 11 A-/N-, 32 A+/N-, 4 A-/N+, 31 A+/N+. Overall survival at 1 year based on subtype was 25% in A-/N- (2/9), 60% in A-/N+ or A+/N- (13/32), and 55% in A+/N+ (10/25). For the 10 pts who survived 2 years, 5 were A+/N- and 5 were A+/N+. 146 pts treated with 1L platinum had RECIST-evaluable disease. ORR was 75% (110/146; 95% CI 68-82%). Median PFS was 7 months with CR/PR and 3.5 months with SD/PD (HR 0.32; 95% CI 0.18-0.56). Median OS was 17 months with CR/PR and 11 months with SD/PD (HR 0.55; 95% CI 0.34-0.9). Mutations in RUNX1, EPHA7, CDKN2A, FLT1 and copy number alterations in FGFR1, CCND1 were enriched in patients with SD/PD (p<0.05). PFS rate at 6 months was 25% in A-N- (1/4), 60% in A-/N+ or A+/N- (9/15), and 55% in A+/N+ (6/11). For the 7 pts who survived 2 years, 3 were A+/N- and 4 were A+/N+. Conclusions: Molecular subtypes defined by ASCL1 and NeuroD1 encompass molecular characteristics that may predict patient outcomes. Further investigation is needed to delineate the underlying biological differences among the various subtypes to help define therapeutic vulnerabilities of each subtype of SCLC. Completion of IHC for ASCL1, NeuroD1 and additional key transcription factors POU2F3 and YAP1 are in progress for the entire cohort. WES and RNA sequencing are occurring in parallel and will be correlated with IHC results and clinical outcomes.
Base excision repair (BER) inhibitor TRC 102 (Methoxyamine) combined with pemetrexed (PEM)-based chemo-radiation (CRT) for locally advanced non-squamous non-small cell lung cancer (NS-NSCLC): Results of a phase I trial.
Authors: Biswas Tithi , Dowlati Afshin , Kunos Charles , Pink John , Oleinick Nancy , Malik Shakun M. , Fu Pingfu , Bruno Debora S. , Bajor David Lawrence , Patel Monaliben , Machtay Mitchell 
Published: May 2020

9027 Background: About 35% of all NSCLC presents with locally advanced disease and chemo-radiation results in 5-year OS of only ~31%. PEM-platinum combination is approved in stage IV NSCLC and has similar efficacy to platinum-etoposide in stage 3 NSCLC and a favorable toxicity profile (Proclaim trial). TRC102 is an oral small molecule inhibitor of BER. TRC102 potentiates the cytotoxicity of antimetabolites and alkylators and reverses chemotherapy resistance by rapidly and covalently binding to chemotherapy-induced abasic sites in DNA. TRC102 increased radio-sensitization by PEM of NSCLC cell lines and H1299 and A549 xenografts. Methods: Between 11/2015 and 5/2019, 15 patients were enrolled in a 3+ 3 design: 12 with stage III and 3 with oligometastatic stage IV NS-NSCLC. The primary objective was to determine dose-limiting toxicities (DLT’s) and recommended Phase 2 dose (RP2D) of TRC102 in combination with PEM, cisplatin and radiotherapy. Secondary objectives were to assess toxicity, tumor response and PFS at 6 months. Based on pre-clinical data, PEM-TRC102 was given on day 1, and cisplatin/radiotherapy was initiated on day 3. This schedule was duplicated on day 21 and day 23 of the second cycle. After completion of radiotherapy, two additional cycles of PEM-cisplatin were given. Toxicities were assessed by NCI CTACAE version 4 and 5. Results: Median patient age was 69 years (45-79) and median follow up was 16.6 months (3.1-38.6). There were no DLTs or grade 5 toxicity. Hematologic and GI toxicities were the most common adverse events (Table) and radiation pneumonitis was not seen. The RP2D of TRC102 was 200 mg when given with cisplatin/radiotherapy and PEM. Of 15 evaluable patients, 3 had CR (20%) and 12 had PR (80%). The 2-year PFS rate was 49%. Conclusions: PEM-TRC102 combined with cisplatin/radiotherapy in non-squamous NSCLC was safe and well tolerated, and did not cause safety signals beyond those expected from CRT. Preliminary response data and PFS in this cohort was encouraging. A phase 2 trial, integrating post-CRT immunotherapy with this aggressive DNA-damaging regimen is warranted. Clinical trial information: NCT02535325. [Table: see text]
Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation.
Authors: An Josiah , Yan Melissa , Yu Nanmeng , Chennamadhavuni Adithya , Furqan Muhammad , Kruser Timothy , Sita Timothy L , Nguyen Ryan , Feldman Lawrence Eric , Pasquinelli Mary , Hanna Nasser H. , Abu Hejleh Taher 
Published: May 2020

9033 Background: STK11 mutation ( STK11m) in patients with stage IV NSCLC is associated with inferior survival and poor response to immune check point inhibitors (ICI). The significance of STK11m in patients (pts) with stage III NSCLC treated with concurrent chemoradiation (CCRT) with and without consolidation ICI is unknown. Methods: Patient demographics, disease characteristics, treatment received and outcomes in pts with stage III NSCLC that harbor STK11m were retrospectively reviewed from 4 cancer centers. A cohort of pts with stage III NSCLC and wild type STK11 (STK11w) from the University of Iowa served as a comparison group. SPSS version 25 was used for data analysis. Results: 75 pts with stage III NSCLC who had gene sequencing were included. 16/75 (21%) had STK11m. The clinical characteristics for the 16 STK11m and 59 STK11w pts showed ( STK11m vs. STK11w): mean age: 58 vs. 64 yrs, non-squamous histology: 11/16 (69%) vs. 37/59 (63%), KRAS co-mutation: 6/16 (38%) vs. 11/59 (19%), TP53 co-mutation: 9/16 (56%) vs. 15/59 (25%), PD-L1 ≥ 50%: 2/16 (13%) vs. 10/59 (17%), received CCRT 11/16 (69%) vs. 59/59 (100%) and consolidation ICI 6/16 (38%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 7 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). Progression free survival (PFS) for the STK11m vs. STK11w pts who received CCRT but not ICI was (4.2 vs. 34.3 months, respectively. P = 0.168), for the STK11m vs. STK11w pts who received CCRT and ICI was (11.3 vs. 17.5 months, respectively. P = 0.174), and for the STK11m vs. STK11w pts who received CCRT regardless of receiving ICI (11.3 vs. 32.9 months, respectively. P = 0.021). The median overall survival for STK11m pts (16 pts) was 25.5 months (95% CI, 13.7 to 37.2) while not yet reached for the STK11w group. Conclusions: In stage III NSCLC, STK11m was associated with inferior clinical outcomes. Larger studies are needed to identify the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.
Real-world treatment patterns and clinical outcomes in EGFR-mutant unresectable locally advanced NSCLC (LA-NSCLC): A retrospective multicenter study of 367 patients.
Authors: Bi Nan , Wang Luhua , Xu Kunpeng , Ge Hong , E Mingyan , Zhang Li , Cao Jianzhong , Zhang Xu , Xia Bing , Zhao Lujun , Li Jiancheng , Hu Chen 
Published: May 2020

9047 Background: The chemoradiation therapy (CRT) is the standard care for unresectable LA-NSCLC. The addition of EGFR-TKIs in first-line treatment of EGFR-mutant subpopulation is debatable. Methods: We retrospectively collected data for patients with unresectable stage III NSCLC harboring EGFR mutations from nine major academic cancer institutions in China from Jan 2012 to December 2018. Patients with ALK rearrangements were excluded. Patients were categorized into three subgroups according to the primary treatment: 1) RT+TKI: Combined RT and EGFR-TKI with/out chemotherapy; 2) no TKI: CRT alone; 3) upfront TKI: EGFR-TKI followed by RT at local-regional progression. PFS and OS were calculated from the date of diagnosis. Log-rank test was used to assess for differences and Cox proportional hazards model was used to adjust for covariates. Results: A total of 367 patients met selection criteria were included in the study. Patients receiving TKI were older (≥60 years: 54.7% TKI v 36.4% and RT+TKI 33.3% CRT; P = 0.001), and more patients receiving CRT had uncommon EGFR mutations ( 10.3% CRT v 2.3% RT+TKI and 4.0% TKI; P = 0.020). Other baseline characteristics were well balanced among groups. With a median follow-up of 40.8 months, the median PFS and OS were 16.6 and 55.4 months for the entire cohort. The median PFS and OS for the three subgroups were shown in the table. On multivariable analysis, after adjusting for age, KPS status, smoking status, stage, and type of EGFR mutations, TKI+RT was independently associated with improved PFS (HR, 0.57; 95% CI, 0.41 to 0.78 ) and OS (HR, 0.61; 95% CI, 0.39 to 0.97) relative to upfront TKI; TKI+RT was also associated with improved PFS (HR, 0.38; 95% CI, 0.27 to 0.54 ) relative to CRT, but not OS (HR, 0.66; 95% CI, 0.40 to 1.11). Conclusions: The use of upfront EGFR-TKI with deferred RT at progression was associated with inferior OS in patients with EGFR-mutant unresectable LA-NSCLC. First-line use of radiotherapy and EGFR-TKI was associated with the longest PFS and OS, which requires further prospective, randomized evaluation. [Table: see text]