tbuckley/cabot-search huggingface dataset:
A randomized phase 3 study of abemaciclib versus erlotinib in previously treated patients with stage IV NSCLC with <i>KRAS</i> mutation: JUNIPER.
Authors: Jonathan Wade Goldman, Julien Mazieres, Fabrice Barlesi, Marianna Koczywas, Konstantin H. Dragnev, Tuncay Göksel, Alexis B. Cortot, Nicolas Girard, Claas Wesseler, Helge Bischoff, Ernest Nadal, Keunchil Park, Shun Lu, Alvaro Taus, Manuel Cobo, Karla Hurt, Alan Chiang, Anwar Hossain, William J. John, Luis G. Paz-Ares
Journal: Journal of Clinical Oncology (2018)

9025 Background: Approximately 30% of NSCLC tumors harbor KRAS mutations, for which there is no specific treatment. Abemaciclib is a potent and selective inhibitor of CDK4 & 6 approved for treatment of HR+, HER2- advanced breast cancer. In a Phase 1 study, abemaciclib showed greater clinical activity in patients with advanced NSCLC with KRAS mutant tumors versus KRAS wild type tumors. This study compared abemaciclib with erlotinib, both with best supportive care, in previously treated patients with advanced NSCLC and KRAS mutations. Methods: This was a global, Phase 3, comparator-controlled, multicenter, open-label trial for patients with confirmed stage IV NSCLC, detectable KRAS mutations in codons 12 or 13, with progressive disease after platinum-based chemotherapy and 1 additional line of therapy, measurable disease by RECIST v1.1, ECOG performance status 0-1, and adequate organ function. Patients were randomized 3:2 to receive either abemaciclib 200 mg PO Q12H or erlotinib 150 mg PO Q24H until disease progression or unacceptable toxicity. Primary objective was overall survival (OS). Secondary objectives included progression-free survival (PFS), objective response rate (ORR, complete response + partial response), and safety and tolerability. Results: A total of 453 patients were randomized, 270 to abemaciclib and 183 to erlotinib. Median OS was 7.4 months with abemaciclib and 7.8 months with erlotinib (HR [95% CI]: 0.97 [0.77, 1.22]; stratified log-rank, p = 0.77). Median PFS was 3.6 months with abemaciclib and 1.9 months with erlotinib (HR [95% CI]: 0.58 [0.47, 0.72]; stratified log-rank, p < 0.001). The ORR was 8.9% (95% CI: 5.5, 12.3%) with abemaciclib and 2.7% (0.4, 5.1%) with erlotinib (p = 0.01). The disease control rate was 54.4% (95% CI: 48.5, 60.4%) with abemaciclib and 31.7% (25.0, 38.4%) with erlotinib. There were no new safety signals with abemaciclib in this study. Conclusions: In previously treated patients with stage IV NSCLC harboring KRAS mutations, abemaciclib did not improve OS but demonstrated improvement in PFS and ORR compared with erlotinib. Further molecular subgroup analysis based on abemaciclib’s mechanism of action is underway. Clinical trial information: NCT02152631.
The associated factors of skeletal related events in patients with non-small cell lung cancer.
Authors: Toshiyuki Kozuki, Eiji Nakada, Natsumi Yamashita, Daijiro Harada, Hiromoto Kitajima, Shinsuke Sugihara, Naoyuki Nogami
Journal: Journal of Clinical Oncology (2016)

e21640 Background: Bone metastasis is frequently observed in advanced non-small cell lung cancer (NSCLC) accounting for 30-40%. Bone metastasis is sometimes symptomatic and causes severe pain or paralysis which impairs quality of life. If the patients who are at higher risk of SREs are identified, monitoring of bone metastases might be performed more effectively, which would lead to prevention of significant morbidity. Then, we analyzed the associated factors of skeletal related events in patients with non-small cell lung cancer in Shikoku Cancer Center (Matsuyama, Japan). Methods: We retrospectively reviewed the medical records of NSCLC patients with bone metastasis at initial diagnosis or during the treatment in our institute between January 2011 and February 2015. We extracted the following factors; age, sex, EGFR mutation status, SREs at initial bone metastasis diagnosis, serum LDH and ALP level, the number of bone metastasis, the number of vertebral metastasis, and the other distant metastasis. We performed univariate analyses are conducted with log-rank tests and multivariate analyses with Cox proportional hazard model. Results: Total 181 patients (pts) were analyzed. Male/Female = 94/87, Median age = 66 years old (Range, 25-88). Adenocarcinoma/Squamous cell carcinoma/Large cell carcinoma = 165/14/2. Zoledronic acid and/or denosumab were administrated in 108 pts for bone metastasis. SREs were experienced in total 84 pts (46%). SREs was observed in 50 pts (28%, 60 sites) and 43 pts (24%, 47 sites) at bone metastasis initial diagnosis and during the treatment, respectively. 8 pts, 3 pts, and 1 pt experienced SRE twice, three and four times, respectively. Total 84 pts received the palliative irradiation and 5 pts received surgery. The SREs free survival was 76% and 55% at 1year and 2-year, respectively. The associated factors of SREs were the presence of EGFR mutation and serum LDH level ( ≥ 300U/L) in univariate and multivariate analysis. The hazard ratios were 2.87 (95%C.I. 1.39-5.94, p = 0.004) in EGFR mutation and 2.95 (95% C.I. 1.54-5.64, p = 0.001) in serum LDH ( ≥ 300U/L), respectively. Conclusions: This study demonstrates EGFR mutation and serum LDH ( ≥ 300U/L) level are independent risk factors for the prediction of SREs.
A randomized phase II study to compare the efficacy of upfront bi-monthly rotations between pazopanib (PAZ) and everolimus (EVE) versus sequential treatment of first-line PAZ and second-line EVE until progression in patients with metastatic clear cell renal cell cancer (ccRCC) (ROPETAR trial).
Authors: Geert A. Cirkel, Paul Hamberg, Stefan Sleijfer, Olaf Loosveld, Wouter Dercksen, Maartje Los, John B. A. G. Haanen, Marco Polee, Franchette van den Berkmortel, Maureen J.B. Aarts, Laurens Victor Beerepoot, Gerard Groenewegen, Martijn P. Lolkema, Metin Tascilar, Johanna Elisabeth A. Portielje, Frank PJ Peters, Heinz Josef Klümpen, Vincent van de Noort, Emile E. Voest
Journal: Journal of Clinical Oncology (2016)

4550 Background: Targeted agents have improved survival in ccRCC patients but resistance always develops. Since accumulating evidence suggests that resistance is partially reversible after drug withdrawal we tested the hypothesis that bi-monthly rotations of treatment with PAZ and EVE delays resistance compared with the standard of PAZ followed by EVE at progression. Methods: Phase 2, open-label, randomized (1:1), multicenter study. Eligibility: ≥ 18 years, treatment naive progressive metastatic ccRCC, ECOG PS ≤ 2. First-line treatment consisted of either a bi-monthly alternating treatment schedule with PAZ 800mg/d and EVE 10mg/d (rotating arm, ROT) or PAZ 800mg/day (control arm, CON). After progression according RECIST 1.1 (PD) patients made a final rotation to either PAZ or EVE monotherapy (ROT) or initiated EVE (CON) as second-line treatment. Primary endpoint was survival until first PD or death (PFS1). Secondary endpoints included time to second PD or death (PFS2) and toxicity.Accrual of 100 patients was planned to detect an increase in 1-year PFS of 50 to 80% (power 90%, α = 0.05, 2-tailed test). Results: Between 2012 and 2014, 101 patients were randomized. Overall Memorial Sloan Kettering Cancer Center risk categories (MSKCCrc): favorable 26%, intermediate 58% and high-risk 15%. Baseline characteristics and risk categories were well-balanced. One year PFS1 for ROT was 46% (95% CI:34-62) and 31% (95% CI:20-48) for CON (p = 0.13; 2-sided). Median PFS1 for ROT was 7.4mo (95% CI:5.1-19.0) and 8.9mo (95% CI:6.6-11.9) for CON (p = 0.32). Hazard ratio stratified by MSKCCrc (sHR) for PFS1 was 0.81 (95% CI:0.49-1.32;p = 0.39) in favor of ROT. Median PFS2 for ROT was 23.0mo (95% CI: > 10.9) and 14.5mo (95% CI: > 11.9) for CON. sHR for PFS2 was 1.05 (95% CI:0.59-1.84;p = 0.88). Mucositis (35% vs 8%), anorexia (39% vs 20%) and dizziness (14% vs 0%) were more prevalent in ROT during first-line treatment. Conclusions: Bi-monthly rotating treatment with PAZ and EVE did not lead to a delay in drug resistance, prolonged PFS or less toxicity. Clinical trial information: NCT01408004.
Late complications among adult survivors of neuroblastoma in the St. Jude Lifetime Cohort Study (SJLIFE).
Authors: Carmen Louise Wilson, Cathleen Marie Cook, Tara M. Brinkman, Sujuan Huang, Wayne Lee Furman, Nickhill Bhakta, Leslie L. Robison, Kirsten K. Ness, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2017)

10561 Background: Assessment of late outcomes in neuroblastoma survivors has generally consisted of self-reported health events within retrospective cohorts. We aimed to characterize the health outcomes of a clinically-assessed cohort of long-term survivors of neuroblastoma diagnosed between 1963-2003. Methods: In a cohort of 239 ten-year survivors of neuroblastoma, of whom 137 (57%) underwent comprehensive clinical assessments, chronic conditions were graded using a modified version of the Common Terminology Criteria of Adverse Events, version 4.03. Comparisons were made using 272 clinically assessed community controls. Log-binomial regression was used to compare the prevalence of chronic conditions (grade 1-5) between survivors and controls and to calculate prevalence ratio (PR) and 95% confidence intervals (CI). Mean cumulative count (treating death as a competing risk) of chronic conditions by age was used to estimate cumulative burden with imputation of outcomes for non-clinically assessed survivors. Results: The median age at diagnosis was 0.9 (range: 0.0-14.4) and the median age at follow-up was 31.9 (range: 20.2-54.6) years for clinically assessed survivors. Median age of controls was 34.7 (range: 18.3-70.2). Treatment consisted of chemotherapy (75%), radiation (23%) and surgery (91%). Survivors were more likely than controls to have hearing loss (31.4% vs. 2.9%, PR = 10.7, 95% CI = 5.2-22.0), cardiomyopathy (8.8% vs. 0.7%, PR = 11.9, 95% CI = 2.7-52.5), hypothyroidism (10.9% vs. 5.2%, PR = 2.1, 95% CI = 1.1-4.3) or neurological disorders (56.9% vs. 32.4%, PR = 1.8, 95% CI = 1.4-2.2). At 35 years of age, the cumulative incidence of survivors experiencing at least one grade 3-5 condition was 67.3% (95% CI = 58.3-76.0%). By age 35 survivors experienced, on average, 8.5 (95% CI = 7.6-9.3) grade 1-5 and 2.4 (95% CI = 2.0-2.8) grade 3-5 conditions per 100 survivors, which was higher than the burden of grade 1-5 (3.3 [95%CI = 2.9-3.7]) and grade 3-5 (0.9 [95%CI = 0.7-1.0]) conditions identified among controls. Conclusions: Two-thirds of survivors are affected by severe or life-threatening health conditions. Continued follow-up, screening and intervention provide opportunities to optimize health.
A phase II trial of regorafenib (REGO) in patients (pts) with advanced Ewing sarcoma and related tumors (EWS) of soft tissue and bone: SARC024 trial results.
Authors: Steven Attia, Vanessa Bolejack, Kristen N. Ganjoo, Suzanne George, Mark Agulnik, Daniel A. Rushing, Elizabeth Trice Loggers, Michael B. Livingston, Jennifer A. Wright, Sant P. Chawla, Scott H. Okuno, Denise K. Reinke, Richard F. Riedel, Lara Emily Davis, Christopher W. Ryan, Robert G. Maki
Journal: Journal of Clinical Oncology (2017)

11005 Background: Pazopanib is approved for soft tissue sarcoma pts after failure of other therapy, but there are few subtype-specific data regarding kinase inhibitor activity. We report on a single arm, phase II trial of REGO in advanced EWS. Methods: EWS pts (age &gt; 18, ECOG 0-2, good organ function) who had at least 1 line of therapy and had PD within 6 mo were eligible. Prior oral kinase inhibitors were not allowed. Initial REGO dose was 160 mg PO QD x21 q28d. Dose reductions were employed for toxicity and AEs. The primary endpoint was PFS at 8 weeks (PFS8w) employing RECIST 1.1. Sample size of 30 allowed determination of the difference between PFS8w of 50% vs 25% with alpha = 0.05 and power of 91%. Results: 30 pts (median age 32, range 19-65; M/F = 20/10; ECOG 0/1/2 = 16/13/1; bone, 12; soft tissue, 18; median prior treatments 5, range 1-10) enrolled at 14 US sites (09/2014-03/2016). Most common grade (G3) toxicities were hypophosphatemia (6), hypertension (2), high ALT (2) and 1 each: fatigue, abd pain, diarrhea, hypokalemia, oral mucositis, neutropenia and rash; no G4 toxicities were noted. 13 pts required ≥1 dose reduction, most commonly hypophosphatemia (n = 7); 2 stopped REGO for toxicity. There was 1 death in the 30 day post study period, not REGO related. Median dose at study end: 140 mg (3.5 tabs, range 80-160 mg) 3 wks on/1wk off. 18/30 pts were without PD at 8 wks. Median PFS: 3.6 mo (95%CI 2.8-3.8 mo). PFS8w by KM was 73% (95%CI 57-89%). Best responses: PR/SD/PD/not evaluable of 3/18/7/2, for RECIST RR 10%. Two pts with PR had EWSR1 translocation by FISH; a third had CIC-DUX4. Median duration of response: 5.5 mo (95%CI 2.9-8.0). Median OS is not reached. Conclusions: The substudy met its primary endpoint. REGO toxicity was similar to that seen previously. Enrollment continues in LPS and OGS cohorts, and is being expanded to further study variant EWS without EWSR1-FLI1 fusion. Study of the existing tissue may elucidate which EWS patients may benefit from REGO. Clinical trial information: NCT02048371.
Randomized phase III study comparing non-myeloablative lymphocyte depleting regimen of chemotherapy followed by infusion of tumor-infiltrating lymphocytes and interleukin-2 to standard ipilimumab treatment in metastatic melanoma.
Authors: MarnixMarnix Heimen Geukes Foppen, Marco Donia, Troels Holz Borch, Özcan Met, Christian U. Blank, Loes Pronk, Johannes V. Van Thienen, Inge Marie Svane, John B. A. G. Haanen
Journal: Journal of Clinical Oncology (2016)

TPS9592 Background: Historically, patients with metastatic melanoma had an extremely poor prognosis with a median overall survival (OS) of 6 to 9 months. In 2010, the CTLA4 blocking antibody ipilimumab, showed for the first time, an improvement in median OS and was approved for this stage of disease. Yet, only around 20% of the treated patients benefit long-term. In addition, ipilimumab can cause serious, sometimes life-threatening side-effects and puts a high burden on health costs. Adoptive transfer of tumor-infiltrating lymphocytes (TIL) is another promising new treatment modality for patients with metastatic melanoma. Several independent phase II studies have shown comparable and consistent response rates of around 50%, with very durable responses in patients reaching a complete remission. TIL therapy consists of infusion of high numbers of ex vivo expanded TIL preceded by non-myeloablative (NMA) chemotherapy and followed by high dose interleukin-2 (HD IL-2). Methods: This is an international, open-label, multi-center, phase III study. Patients with irresectable stage IIIc or IV melanoma, between the ages of 18 and 70 years, with one or more resectable metastases summing up to at least 2-3 cm in diameter and adequate organ function, are randomized 1:1 between TIL therapy and ipilimumab. Patients will be stratified according to BRAF V600 mutation status, line of treatment (1st or 2nd line) and treatment center. Patients randomized to TIL will receive NMA chemotherapy consisting of cyclophosphamide (60 mg/kg/day for 2 days i.v.) and fludarabine (50 mg/m2 for 5 days i.v.), intravenous adoptive transfer of > 5x109 TIL followed by HD IL-2 (600.000 IU/kg/dose every 8 hours, maximally 15 doses). Patients randomized to ipilimumab (3 mg/kg i.v.) will receive this once every three weeks, for up to 4 doses. The primary end-point is progression free survival at six months. Secondary endpoints are OS, complete response rate, ORR and safety profile. Enrollment began in September 2014. 168 randomized patients are required to show a 50% increase in PFS at 6 months. Clinical trial information: NCT02278887.
Comparative in vitro testing of povidone-iodine and other commercially available oral antiseptics against common pathogens using current European suspension assay.
Authors: Hanlim Moon, Jun Xian Chua, Nur Humaira Johari, Eng Lee Tan, Sfefan Mueller
Journal: Journal of Clinical Oncology (2016)

e21607 Background: The myelosuppressive and mucosal-damaging consequences of cancer and cancer therapies put patients at high risk of opportunistic bacterial and fungal oral infections. We explored the in vitrobactericidal and fungicidal effect of povidone-iodine (PVP-I) and other oral antiseptic products against common oral pathogens, with focus on a rapid effect (within 30 sec). Methods: Susceptibility of relevant oral bacteria (MRSA and P. aeruginosa [sources of opportunistic infection], S. mutans [associated with tooth decay] and S. sanguinis [marker of healthy oral flora]) and C. albicans was evaluated in vitro using bactericidal and fungicidal quantitative suspension assays (DIN EN 1276 and 1650). Antiseptic products were tested undiluted (lozenges were dissolved 1:1 with water) and at defined dilutions. Pathogens were exposed to the tested antiseptic for 30 sec, neutralized and reduction in survival rate was calculated. A > 4 log fold (99.99%) reduction of C. albicansand > 5 log fold (99.999%) reduction of bacteria represented effective microbicidal activity. Results: PVP-I products (1% and 7.5% gargle and 0.45% throat spray) were highly effective against all pathogens tested, undiluted and at 2:1 and 3:1 dilution. Chlorhexidine 0.2% mouthwash was effective against all pathogens except MRSA undiluted, but was ineffective against MRSA, S. mutans and C. albicans when diluted 4:1. Hexetidine 0.1% mouthwash was effective against only P. aeruginosa (undiluted and 4:1 dilution) and C. albicans (undiluted). 1.2 mg 2,4-dichlorobenzyl alcohol/0.6 mg amylmetacresol lozenges were effective against only P. aeruginosa (at 1:1 and 2:1 dilution) and S. sanguinis(at 1:1 dilution). Thymol, benzydamine lozenges and salt water were ineffective against all pathogens tested. Conclusions: Among tested antiseptics, only PVP-I products were effective against all tested pathogens, with quick onset of action undiluted and at defined dilution. These data may help healthcare professionals in the selection of antiseptics for both prophylaxis and management of oral bacterial infection and candidiasis in cancer and other immunocompromised patients.
Neoadjuvant gefitinib for stage II-IIIA NSCLC with activating EGFR mutation (NCT01833572): an open-label, single-arm, phase II study.
Authors: Ranxia Gong, Haichuan Hu, Haiquan Chen
Journal: Journal of Clinical Oncology (2016)

e20026 Background: This a single arm open label trial is to explore the efficacy and safety of gefitinib as neoadjuvant treatment in stage II-IIIA NSCLC patients with activating EGFR mutation. Methods: Previously untreated patients with clinically or histologically confirmed stage II-IIIA NSCLC harboring activating EGFR mutation in exon 19 or 21 were recruited to receive gefitinib 250mg orally per day for 42 days during the neoadjuvant period. Tumour responses assessments were performed at day 0, day 21 and day 42. Patients receiving benefit (CR, PR or SD) from gefitinib and were evaluated to be resectable would receive surgery. The primary endpoint is objective response rate (ORR). The secondary endpoints included pathologic response rate, radical resection rate, disease free survival (DFS), overall survival (OS), safety and quality of life (QoL). Clinical trial identification: (NCT01833572) Results: From 12th Jul 2013 to 8th Dec 2015, 204 II-IIIA NSCLC patients were screened, 36 patients with EGFR mutation were enrolled (1 patient withdrawn and 4 patients were ineligible). Data of 31 patients was analyzed on 15th Jan, 2016 (Table 1). After gefitinib treatment, ORR was 51.6% (16/31), DCR was 100% (31/31). 29 patients underwent resection surgery and 2 patients didn’t receive surgery (1 patient refusal and 1 patient was not suitable for surgery) . Radical resection rate was 75.9% (22/29). DFS and OS data are immature. 19 patients had rash (grade I-II) and 11 patients had diarrhea (grade I) during gefitinib treatment. Conclusions: Gefitinib as neoadjuvant therapy is a efficacious treatment for EGFR mutant II-IIIA NSCLC patients alongside a tolerable safety profile.. Clinical trial information: NCT01833572.
Radical esophagectomy for thoracic esophageal squamous cell carcinoma followed by adjuvant radiotherapy with or without chemotherapy: Which is more beneficial?
Authors: Yan Tu, Feng Peng
Journal: Journal of Clinical Oncology (2017)

e15597 Background: The current guidelines of the National Comprehensive Cancer Network for thoracic esophageal squamous cell carcinoma(TESCC) are commended no additional treatments after surgery unless the margins are positive.The optimal therapeutic options in TESCC initially treated after surgery remains controversial .This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy(RT) and chemoradiotherapy(CRT) in stage II or III TESCC patients who underwent curative esophagectomy. Methods: From January 2006 to December 2013 , 272 cases with pathological confirmed stage II or III TESCC, who had undergone complete esophagectomy, were eligible for analysis.Of these patients, 148 cases received postoperative CRT–at least 2 courses of cisplatin plus fluorouracil or paclitaxel– while the other 124 cases received RT(≥45Gy) alone.The primary end point was overall survival (OS) and the secondary endpoint were disease free survival (DFS) and toxic reactions. Results: In CRT and RTgroups,the OS rates at 1, 3 and 5 years were 91.8% vs 83.8% , 51.3% vs 31.5% and 25% vs 9.68% , respectively(P &lt; 0.01).In CRT and RTgroups, the median OS were 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively(P = 0.213), and the median DFS were 23 months (95% CI, 14.7 to 31.3 months) and 16 months (95% CI, 13.3 to 18.6 months),respectively(P = 0.155). Univariate and multivariate analyses showed stage, N stage and the number of lymph nodes removed were independent prognostic factors for OS. There were no statistically differences between the two groups for both recurrence and metastasis rates(P &gt; 0.05). Toxic reactions, including myelosuppression and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P &lt; 0.05). No significant differences in incidence of other toxic reactions were found between the two groups. Conclusions: Our results indicate that, in stage II or III TESCC patients, compared with postoperative RT,CRT has a tendency to improve survival. Toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.