tbuckley/cabot-search huggingface dataset:
Atezolizumab (atezo) in platinum-treated locally advanced or metastatic urothelial carcinoma (mUC): Outcomes by prior therapy.
Authors: Jose Luis Perez-Gracia, Yohann Loriot, Jonathan E. Rosenberg, Thomas Powles, Andrea Necchi, Syed A. Hussain, Rafael Morales, Margitta Retz, Guenter Niegisch, Ignacio Duran, Christine Theodore, Enrique Grande, Ann Christine Thastrom, Shi Li, Oyewale O. Abidoye, Michiel Simon Van Der Heijden
Journal: Journal of Clinical Oncology (2017)

323 Background: Atezo is approved in the US for mUC and non-small cell lung cancer after prior treatment with chemotherapy. &gt; 40% of mUC pts in the Phase 2 IMvigor210 study received ≥ 2prior metastatic regimens (Rosenberg, Lancet 2016). This analysis was performed to assess the impact of prior therapy on atezo outcomes in mUC. Methods: mUC pts in the platinum-pretreated IMvigor210 cohort (NCT02108652) received atezo 1200 mg IV q3w until loss of clinical benefit. Study endpoints analyzed by the number of prior treatment regimens included RECIST v1.1 ORR (central review), complete response (CR) rate, median durations of response (mDOR) and survival (mOS) and adverse event rate. Results: Evaluable pts (N = 310) had a median age of 66 years, and 78% had visceral mets (31% liver). 82% of pts had prior systemic treatment for mUC; number of prior regimens ranged from 1 to ≥ 4 (Table). 73% of pts received prior cisplatin, and 26% had carboplatin (no cisplatin). Objective responses, including CRs, occurred regardless of the number of prior therapies and were ongoing in 65% of responders at the July 4, 2016 data cut off (median follow-up, 21 mo [range, 0.2+-24.5]). mDOR was not reached in any subgroup based on number of treatments, except in pts who received only perioperative chemotherapy (mDOR, 16 mo [95% CI: 6.2, NE]). Similarly, mOS was generally consistent despite number of prior regimens (Table). Atezo remained generally well tolerated with similar overall safety and tolerability by line of therapy. Conclusions: Clinically meaningful benefit was observed in pts treated with atezo notwithstanding number of prior systemic mUC regimens. Minimally and heavily pre-treated pts had durable responses, encouraging OS and no major differences in safety signals. Clinical trial information: NCT02108652. [Table: see text]
A phase II study of atezolizumab (atezo) with or without bevacizumab (bev) versus sunitinib (sun) in untreated metastatic renal cell carcinoma (mRCC) patients (pts).
Authors: David F. McDermott, Michael B. Atkins, Robert J. Motzer, Brian I. Rini, Bernard J. Escudier, Lawrence Fong, Richard Wayne Joseph, Sumanta K. Pal, Mario Sznol, John D. Hainsworth, Walter Michael Stadler, Thomas E. Hutson, Alain Ravaud, Sergio Bracarda, Cristina Suarez, Toni K. Choueiri, YounJeong Choi, Mahrukh A. Huseni, Gregg Daniel Fine, Thomas Powles
Journal: Journal of Clinical Oncology (2017)

431 Background: While targeting VEGF improves outcomes for mRCC pts, resistance invariably develops, often within the first year. Here, we describe the efficacy and safety of atezo (anti-PD-L1) with bev (anti-VEGF) and atezo monotherapy vs sun (TKI) in first-line mRCC. Methods: Treatment-naïve mRCC pts were enrolled in a hypothesis generating Ph II study (IMmotion150; NCT01984242) and randomized to atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w, atezo alone or sun 50 mg PO QD 4 wk on/2 wk off. Crossover to atezo + bev after disease progression was allowed for pts receiving atezo or sun. PD-L1 expression was scored on tumor-infiltrating immune cells (IC, SP142 IHC assay). Coprimary endpoints were PFS (RECIST v1.1 by independent review [IRF]) in ITT pts and pts with PD-L1 expression on ≥ 1% of IC (PD-L1+). Results: Baseline characteristics were comparable across arms and between ITT and PD-L1+ pts. The majority of sun and atezo pts subsequently received atezo + bev. Median survival follow up was 20.7 mo. The PFS HR in ITT pts for atezo + bev vs sun was 1.00 and 1.19 for atezo vs sun. In PD-L1+ pts, the PFS HR for atezo + bev vs sun was 0.64 and 1.03 for atezo vs sun (table). Tx-related Gr 3-4 AEs were seen in 40%, 16% and 57% of pts in the atezo + bev, atezo and sun arms, respectively. AEs leading to death occurred in 3%, 2% and 2% of pts, respectively. Conclusion: Atezo + bev resulted in encouraging antitumor activity in the PD-L1+ subgroup of first-line RCC pts. Atezo + bev safety is consistent with the known profile of atezo and bev individually. The clinical benefit of atezo + bev vs sun will be evaluated in the ongoing Ph III study IMmotion151 (NCT02420821). Clinical trial information: NCT01984242. [Table: see text]
A prospective randomized phase III, double-blind, placebo-controlled study of thalidomide in extended-disease (ED) SCLC patients after response to chemotherapy (CT): An intergroup study FNCLCC Cleo04 - IFCT 00–01
Authors: J. L. Pujol, J. L. Breton, R. Gervais, M. Tanguy, E. Quoix, P. David, H. Janicot, A. Depierre, S. Gameroff, D. Maraninchi
Journal: Journal of Clinical Oncology (2006)

7057 Background: This study aimed at determining whether or not thalidomide prolongs survival of patients (pts) suffering from SCLC. Methods: Eligibility consisted of previously untreated ED-SCLC, age &lt;70 years, PS ≤2, weight loss &lt;10% and, for women, post-menopausal status. Pts were registered in the study and received two courses of PCDE given 4 weeks apart with G-CSF primary prophylaxis recommended. Afterwards, pts who experienced a response were randomized to receive four additional cycles of PCDE plus thalidomide, (400 mg daily) or placebo. The planned accrual was 200 randomised pts in order to detect a 20% survival improvement. Results: The study was shortened with final analysis performed taking into account 119 registered pts (low accrual). There were 4 toxic-deaths (3.3%). Tumour assessment performed after the first two CT courses demonstrated 11 complete responders and 86 partial responders (81.4% overall response rate). Among these pts, 92 were randomly assigned, 49 in the thalidomide group and 43 in placebo group. The 5 remaining pts were not randomised due to poor recovery from previous CT. Pre-study pts’ characteristics did not differ between the two groups. The planned six cycles of PCDE were delivered to an equal proportion of pts in both groups (75.5% versus 74.4%). Mean ± SD exposure duration to thalidomide was 4.5 months ± 2.7 and to placebo 5.1 ± 2.4 (NS). Reasons for withdrawal differed between the two groups with toxicity as main reason for thalidomide (55.3% versus 35%) and disease progression as main reason for placebo (43% versus 62%; p = 0.06). In Cox model of overall survival within the 9 months following randomisation, pts allocated to the thalidomide group had the longest survival (HR of death for pts in the thalidomide group: 0.48 [95% CI: 0.24–0.93]; p = 0.03; median survival from randomisation: 11.7 versus 8.7 months for thalidomide and placebo groups respectively); Conclusion: Thalidomide prolongs survival of pts with SCLC after response to CT. This study is a clue in favour of angiogenesis process as therapeutic window in SCLC therapy. Supported by the French League against Cancer. No significant financial relationships to disclose.
Multi-agent and single-agent chemotherapy in stage IV pancreatic cancer: An NCDB analysis.
Authors: Aabra Ahmed, Ryan W Walters, Timothy Dean Malouff, Lakshmi Manogna Chintalacheruvu, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2017)

231 Background: Cartright et al (2014) examined 2,422 patients in the iKnowMed database and found that patients with advanced pancreatic cancer lived longer with multi-agent chemotherapy compared to single-agent chemotherapy (11.2 months vs 7.2 months). Our goal was to compare survival of patients with stage IV pancreatic cancer receiving multi-agent, single-agent, or no chemotherapy using a significantly larger sample of patients identified in the National Cancer Database (NCDB). Methods: We identified 86,048 patients with stage IV pancreatic cancer. Between-chemotherapy survival differences were estimated by the Kaplan-Meier method and associated log-rank tests; Tukey-Kramer adjusted p &lt; .05 indicated statistical significance. Results: Patients receivingmulti-agent chemotherapy were more likely to have private insurance than single-agent and no chemotherapy patients (49.9% vs. 33.0% vs. 22.9%, respectively), live in an area with a median income of $63,000+ (36.9% vs. 30.2% vs. 28.4%, respectively), receive treatment at an academic center (43.3% vs. 34.5% vs. 32.8%, respectively), and have no comorbidities (72.9% vs. 66.9% vs. 61.1%, respectively). Statistically significant survival differences were indicated between all chemotherapy groups (all adjusted p &lt; 0.05), such that patients receiving multi-agent chemotherapy had the longest survival followed by patients receiving single-agent chemotherapy and patients receiving no chemotherapy (median survival = 7.4, 4.9, and 1.4 months, respectively). A larger proportion of patients receiving multi-agent chemotherapy were alive at 6, 12, and 24 months relative to patients receiving single-agent or no chemotherapy. Conclusions: Our study is the largest to show the benefit of multi-agent chemotherapy over single-agent chemotherapy for stage IV pancreatic cancer, as well as analyze the demographics of patients receiving differing chemotherapy treatments. [Table: see text]
Dose-dense (DD) cyclophosphamide, methotrexate, and fluorouracil (CMF) at 14-day intervals: A pilot study of every 14- and 10–11-day dosing intervals for women with early-stage breast cancer
Authors: P. Drullinsky, M. N. Fornier, S. Sugarman, G. D'Andrea, T. Troso-Sandoval, A. D. Seidman, J. Yuan, S. Patil, L. Norton, C. Hudis
Journal: Journal of Clinical Oncology (2009)

590 Background: CMF (C 600 mg/m 2 , M 40 mg/m 2 , F 600 mg/m 2 ) is an option for adjuvant therapy for patients with low risk early stage breast cancer. DD regimens as predicted by mathematical models of cancer growth and treatment response are superior. We previously demonstrated the safety of DD EC (epirubicin/cyclophosphamide) followed by paclitaxel at 10–11 day (d) intervals. We investigated the feasibility of administering DD adjuvant CMF every 14 d and then every 10–11 d in a 2-stage phase II trial. Methods: An initial cohort (A) was treated q 14 d with PEG-filgrastim (Neulasta) support. A second cohort (B) was treated every 10–11 d with filgrastim/Neupogen x 5 d and then, based on feasibility, modified (cohort C) to use 7 d filgrastim. The primary end point was feasibility defined as having ANC &gt; 1.5 x 10 3 /uL on day 1 of planned treatment for all 8 cycles with no grade 3 or higher non-hematologic toxicity. All three cohorts were tested using a Simon's two-stage optimal design with type I and type II errors set at 10%. This design would effectively discriminate between true tolerability (as protocol-defined) rates of&lt; 60% and&gt; 80%. Cohort A: 38 pts with early stage breast cancer were accrued from 3/2008 though 6/2008. Cohort B: 7 pts were accrued from June 2008 through August 2008. Cohort C: Is still open with 16 pts accrued from August 2008 through December 5, 2008. Results: Median age 51: range 38 to 78. Cohort A: 29/38 pts completed 8 cycles of CMF. The regimen was considered feasible. 2 other pts completed 7 cycles and were withdrawn for depression and grade 2 transaminitis. The 7 other pts completed between 1 and 6 cycles of CMF were withdrawn as follows: 3 personal, 1 (grade 3) bone pain, 2 allergy unrelated to CMF, and 1 seizure. Cohort B: 7 pts were accrued. 6 out of 7 pts could not complete 8 cycles of chemotherapy secondary to neutropenia and 1 secondary to grade 3 ALT elevation. Cohort C: Accrual has not been completed. 16 pts are currently enrolled. Conclusions: Dose dense adjuvant CMF is feasible at 14 d intervals with PEG-filgrastim support. Adjuvant CMF every 10–11 days with filgrastim given for 5 days beginning day 2 is not feasible. Accrual is ongoing for CMF at 10–11 days with filgrastim x 7 days. Updated results will be available for Cohort C. [Table: see text]
Cardiac toxicity prevention in non-metastatic breast cancer patients treated with anthracycline-based chemotherapy: A randomized, placebo controlled, phase III trial—SAFE trial.
Authors: Icro Meattini, Roberto Tarquini, Calogero Saieva, Alice Valoriani, Pierluigi Bonomo, Isacco Desideri, Mauro Loi, Vieri Scotti, Carla De Luca Cardillo, Stefano M. Magrini, Gianfranco Gensini, Lorenzo Livi
Journal: Journal of Clinical Oncology (2015)

TPS1100 Background: Anthracyclines and trastuzumab play a key-role in preoperative and adjuvant breast cancer (BC) treatment, and showed a significant survival benefit in several trials. Although acute cardiac toxicity is infrequent and usually reversible in a dose-dependent manner, published data evidenced a clinically relevant early late cardiac toxicity, with a chronic progressive deterioration of left ventricular ejection fraction (LVEF), up to congestive heart failure (CHF). Late toxicity occurs in most cases within the first year following chemotherapy completion, but an echocardiographic monitoring is strongly recommended even after a longer time. Recent studies highlighted that the evaluation of myocardial strain could be a refined predictive marker of early cardiac dysfunction after anthracyclines exposure. The aim of our study is to find out the best approach as cardiac toxicity prevention in non-metastatic BC patients undergoing anthracycline-based chemotherapy, with or without subsequent anti-HER2 therapy. Methods: This is a randomized phase III, four-arm, single-blind, placebo-controlled study that aims to evaluate the effect of bisoprolol (5 mg, twice daily), ramipril (5 mg, twice daily), or both drugs, compared to placebo, on anthracycline therapy induced LVEF dysfunction for non-metastatic disease. Cardioprotection is administered for one year, or until the end of trastuzumab (if HER2 positive). All patients undergo cardiac surveillance with echocardiogram and speckle tracking strain at baseline and every three months, until 2 years. Primary endpoint is maximum change in LVEF. Assuming a cardiac toxicity incidence of 40%, with a 15% reduction in both arms to reach the outcome, a sample of 120 patients per arm provides a 90% statistical power, for a total of 480 enrolled patients. The analysis is based on intent-to-treat. Exclusion criteria are: history of CTCAE (v.4) grade > 2 symptomatic CHF, previous myocardial infarction, significant symptoms (grade > 2) relating to LVEF dysfunction, valvular disease, cardiac arrhythmia (grade > 3). Clinical trial information: NCT2236806.
Combining survival and toxicity effect sizes from clinical trials into an interpretable, quality-adjusted survival effect size estimate of treatment efficacy.
Authors: Jeff A. Sloan, Brittny Major, Paul J. Novotny, Axel Grothey, Randolph Marks, Daniel J. Sargent, Amylou C. Dueck
Journal: Journal of Clinical Oncology (2014)

6630 Background: How can a clinician combine survival and toxicity data to interpet treatment benefit? Quality adjusted life years (QALYs) attempts to account for both the quality and quantity of life lived but interpretation and power considerations are barriers to implementation. We developed a new method by extending the ½ standard deviation approach to assessing clinical significance to combine survival and toxicity clinical trial data into a single quality-adjusted survival effect size (QASES). Methods: QASES is a weighted combination of the survival and toxicity effect sizes based on differences in survival and toxicity using the ½ standard deviation method. We demonstrate the QASES method on 20 exemplary oncology clinical trials involving brain, breast, colorectal, lung, melanoma and pancreatic tumors. One example is a phase III clinical trial carried out by the North Central Cancer Treatment Group, NCCTG 89-20-52 (Alliance), which randomized patients to once-daily thoracic radiotherapy (ODTRT) versus twice-daily treatment of thoracic radiotherapy (TDRT) for the treatment of lung cancer. Results: The ODTRT (TDRT) arms had non-significantly different median survival times of 22 (20) months.(p=0.49) but strikingly different toxicity rates of 39% (54%), (p<.05). The combined QASES of 0.18 standard deviations is equivalent to a significant 5.7 months advantage in quality-adjusted survival for the ODRT arm over the TDRT treatment arm (22 (16.3) months, p<0.05). Similar results will be presented for the four possible case combinations of significant/non-significant differences in survival and toxicity data using 20 completed clinical trials including the CLEOPATRA and FLAGS trials. Conclusions: The QASES approach allows for an intuitively appealing and mathematically simple and robust approach to combining survival and toxicity data. Clinicians can use QASES to interpret and communicate the findings of oncology clinical trials to patients by weighing both the survival and toxicity information into a single quality-adjusted estimate of survival.
A phase 2 trial of minocycline versus placebo to prevent neuropathy in patients (pts) with multiple myeloma (MM).
Authors: Sheeba K. Thomas, Tito R. Mendoza, Patrick M. Dougherty, Loretta A. Williams, Xin Shelley Wang, Seema Prasad, Nina Shah, Jatin J. Shah, Michael Wang, Donna M. Weber, Robert Z. Orlowski, Sergio Giralt, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2014)

e20669 Background: Peripheral neuropathy is a dose limiting toxicity with bortezomib (Bz) in treating multiple myeloma (MM). Dosing schedule and route of administration changes have reduced its severity, but Bz-associated neuropathy remains debilitating for many patients (pts). Minocycline (M) is a widely used and inexpensive antibiotic that exhibits neuroprotective effects in animal models. We evaluated the potential of M to prevent deterioration of peripheral nerve (PN) function and reduce neuropathic symptoms in MM pts receiving a Bz-containing regimen. Methods: Eligible pts for this single institution, randomized, blinded, placebo-controlled trial were pts with MM receiving induction with twice-weekly Bz. Pts were randomized to receive M (100 mg orally twice daily) or placebo (P) for 10 weeks. Primary endpoint was change in PN function between baseline and week 10, as measured by change in touch detection threshold. Change in patient-reported numbness was assessed by ratings on a 0-10 scale. Covariates included route of Bz administration, baseline symptoms, age, gender, race, BMI, performance status, comorbidity index, and analgesics. Results: Of 79 pts enrolled, touch detection measurements and symptom data are available in 36 (P=17, M=19) and 41 (P=20, M=21), respectively. There were no significant differences in clinician-rated toxicity between groups. No significant difference in observed fingertip touch detection was detected (P=0.02 vs M=0.03, 95%CI, -0.19, 0.17, effect size=0.05). Mean increase in numbness from baseline to week 10 was 1.52 (SD=2.36) and 0.70 (1.95) for the P and M groups, respectively. The observed absolute group difference of 0.82 in favor of minocycline was not statistically significant (95% CI: -0.55, 2.19, p<0.23) but equivalent to an effect size of 0.49. Conclusions: Deterioration of PN function could not be detected over the 10 week study period in either group, impeding quantitative evaluation of M’s neuroprotective potential. Still, we found a detectable, though non-statistically significant, positive signal in patient-reported numbness. Given M’s tolerability and availability, further evaluation in a larger study is warranted. Clinical trial information: NCT01283997.
A randomized double-blind phase III pivotal study of febuxostat (FEB) versus allopurinol (ALL) in the prevention of tumor lysis syndrome (TLS): Florence study.
Authors: Michele Spina, Zsolt Nagy, Josep M. Ribera, Massimo Federico, Igor Aurer, Karin Jordan, Gabriela Borsaru, Alexander S. Pristupa, Alberto Bosi, Sebastian Grosicki, Nataliia L. Glushko, Dusan Ristic, Janos Jakucs, Jiri Mayer, Eduardo M. Rego, Simone Baldini, Simona Scartoni, Cecilia Simonelli, Angela Capriati, Carlo Alberto Maggi
Journal: Journal of Clinical Oncology (2014)

9641^ Background: Tumor lysis syndrome (TLS) is an oncologic emergency characterized especially by elevated serum uric acid (sUA). FEB is an orally administerd selective xanthine oxidase inhibitor to reduce sUA. Methods: This was a randomized, double blind phase III trial of FEB vs ALL in terms of control of sUA level and preservation of renal function in patients undergoing chemotherapy (CT) for hematologic malignancies at intermediate to high risk of TLS. Patients werestratified according to TLS risk and sUA level to FEB or ALL starting from 2 days prior CT and continued for 7-9 days. Assigned treatment was blinded, while daily dose level (low/standard/high containing ALL 200/300/600 mg or fixed FEB 120) was upon investigator’s choice. Primary endpoints were sUA area under the curve (AUC sUA1-8) and change in serum creatinine (sC) level both from baseline to Day 8, analyzed through ANCOVA including treatment and stratification factors as covariates. Secondary endpoints were response rate (sUA ≤ 7.5 mg/dL from CT start to Day 8), incidence of laboratory and clinical TLS and safety. The study was run in 79 sites in Europe and Brazil (NCT01724528). Results: 346 patients were included with similar baseline demographics in both groups. 82.1% of patients were at intermediate risk of TLS, 87.6% had a baseline sUA ≤ 7.5 mg/dl and 82.7% received standard dose level. Intention to treat (ITT) analysis: mean AUC sUA1-8 (mgxh/dl) was significantly lower in FEB arm (514.0 ± 225.71 vs 708.0 ± 234.42; p < .0001). No significant difference in mean sC change(%) occurred between FEB and ALL arms (-0.83 ± 26.98 vs -4.92 ± 16.70 respectively, p=0.0903). No significant difference was detected among secondary efficacy endpoints. Incidence of all adverse events (AEs) and related AEs was 67.6% vs 64.7% and 6.4% vs 6.4% in FEB and ALL arm, respectively. Conclusions: In this largest TLS prevention trial FEB proved to be significantly superior over ALL with a 28% lower exposure to sUA during CT. As no dose adjustment of FEB in patients with preexisting mild or moderate renal impairment is necessary makes FEB a preferable preventive measure of TLS. Clinical trial information: NCT01724528.