tbuckley/cabot-search huggingface dataset:
Randomized phase II study of docetaxel plus vandetanib (D+V) versus docetaxel followed by vandetanib (D-V) in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (OC): SWOG S0904.
Authors: Robert L. Coleman, James Moon, Anil Sood, Donna Branham, James Edwin Delmore, Albert J. Bonebrake, Garnet L Anderson, David Samuel Alberts, Maurie Markman
Journal: Journal of Clinical Oncology (2012)

5015 Background: Antiangiogenesis therapy has led to antitumor effects both preclinically and clinically. Vandetanib (V) is an oral tyrosine kinase inhibitor of VEGFR-2/3, EGFR and RET. These targets are of interest in OC care, as targeting has shown anti-tumor efficacy, particularly in combination with taxanes. We explored the efficacy, safety, and toxicity of docetaxel (D) and V in women with recurrent OC. Methods: Women with resistant, refractory, or progressive/persistent OC were eligible for this randomized phase II study provided they had not received D or V for recurrent disease. Patients were allowed to receive other anti-VEGF targeted agents for primary therapy (stratification variable). Up to 3 additional cytotoxic regimens for recurrence were allowed. Patients were allocated 1:1 to D(75 mg/m 2 , I.V.)+V (100 mg daily, p.o.) or D(75 mg/m 2 ). Patients receiving single agent D were allowed to crossover to V upon progression (D-V). The primary endpoint was PFS. Other objectives were: OS, objective response (ORR), and frequency/severity of adverse events. The study was designed with 84% power to detect a 1.55 PFS hazard ratio using a one-sided P of 0.1. Results: 131 patients were enrolled; 5 were excluded (1 ineligible, 4 eligible but untreated). 9% had received prior anti-angiogenic therapy. 61 patients on D+V were assessable for toxicity; 19 (31%) had treatment-related G4 events, primarily hematologic. Similarly, 17 (26%) of 65 patients receiving D alone had G4 events, primarily hematologic. 34 (52%) patients crossed over to V; no G4 events were recorded among 32 evaluable patients. G3 diarrhea was observed in 14% of D+V patients; 5% D-V patients. G3 acneiform rash occurred in 2% and 0%, respectively. The median PFS estimates were 3.0 mos (D+V) vs 3.5 (D-V); HR (PFS): 0.98 (80% CI:0.75-1.27). For OS, the median estimates were 14 mos (D+V) vs 12 mos (D-V); HR (OS):0.84 (80% CI:0.56-1.28). ORR was 14% and 17%, respectively. Crossover V response was 4% (1/27 measurable patients). Conclusions: D+V was well tolerated in this population however, did not prolong PFS with respect to D.
Phase I/II study of the combination of inotuzumab ozogamicin (CMC-544) with low-intensity chemotherapy in patients (pts) with acute lymphoblastic leukemia (ALL).
Authors: Nitin Jain, Susan Mary O'Brien, Deborah A. Thomas, Elias Jabbour, Stefan Faderl, Sergernne York, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2013)

7092 Background: Older pts with ALL have a significantly worse outcome. This is primarily due to poor tolerance of intensive chemotherapy which results in ineffective delivery of induction-consolidation-maintenance chemotherapy. Addition of targeted non-myelosuppressive therapy to effective low-intensity chemotherapy might improve outcome. CD22 expression occurs in &gt;90% of pts with ALL. Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody bound to a toxin, calecheamicin, and has shown single-agent activity in relapsed/refractory ALL (Kantarjian, Lancet Oncology 2012). Methods: Pts ≥60 years (yrs) with newly-diagnosed B-cell ALL were eligible. The chemotherapy was low-intensity hyper-CVAD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, ara-C at 0.5 g/m2 x 4 doses). Rituximab and intrathecal chemotherapy were given for first 4 courses. IO was given on day 3 of each of the first 4 courses. First 6 pts received 1.3 mg/m2 for cycle 1 followed by 0.8 mg/m2 for subsequent cycles; pts 7 onwards received 1.8 mg/m2 for cycle 1 followed by 1.3 mg/m2 for subsequent cycles. Results: Eleven pts (7 men, 4 women) have been treated so far. Median age is 70 yrs (range 60-79). Median follow-up is 8.2 months (mos). Grade 3-4 non-hematological toxicity included 2 pts with grade 3 LFT elevation. Seven pts had one or more infections. No dose-limiting toxicity was observed. Ten of 11 pts (91%) achieved complete remission (CR). All pts achieving CR have also achieved flow-cytometric MRD negative status and continue to be on study in CR anywhere from 1.0 to 12.4 mos. There have been no relapses. One patient did not achieve CR and died 2 mos later after receiving a salvage regimen. This is the only death on the study. Six-month disease-free and overall survival are 90% and 90%, respectively. Conclusions: Combination of IO with low-intensity chemotherapy is safe and shows very encouraging results (91% CR) in the frontline setting in elderly pts with ALL. These results appear to be better than those achieved with chemotherapy only approach and may become the new standard of care for frontline treatment of elderly pts with ALL. Clinical trial information: NCT01371630.
A novel biomarker panel examining response to gemcitabine (G) with or without erlotinib (E) for pancreatic cancer (PA) therapy in NCIC clinical trials group PA.3.
Authors: David Shultz, Jonathan Pai, Madeline Sydney Graber, Gregory M. Heestand, Daniel Tandel Chang, Wendy R. Parulekar, Dongsheng Tu, Malcolm J. Moore, Albert Koong
Journal: Journal of Clinical Oncology (2014)

4133 Background: NCIC Clinical Trials Group PA.3 (NCIC CTG PA.3) was a randomized control trial that demonstrated an overall survival (OS) benefit in patients receiving E in addition to G for locally advanced or metastatic PA. Prior to therapy, patients had baseline plasma samples drawn and archived for future study. Methods: By using the multiplex capabilities and high sensitivity detection of the proximity ligation assay (PLA), a probe panel was built from commercially available antibodies capable of quantifying 35 key proteins, selected from a global genetic analysis of pancreatic caners followed by a k-means clustering, from 20 uLof patient plasma. To determine if any of these proteins independently associated with OS, multivariate Cox models adjusting for gender, age, race, stage, and pain intensity at baseline were used. Results: Of the 559 eligible patients, 483 had samples available for study. Samples were randomly allocated into training (T) (253) and validation (V) sets (230). Elevated levels of interleukin-8 (IL-8) was the only protein found independently associated with lower OS in patients treated with G alone in both T and V sets, while elevated levels of IL-8, carcinoembryonicantigen (CEA), and hypoxia-inducible factor 1-alpha (HIF-1 alpha) were the proteins in patients treated with G+E or among patients from both treatment arms. Conclusions: PLA is a powerful tool for identifying potential biomarkers from archived, small volume serum samples. These data suggest that pancreatic cancer patients with low IL-8, CEA, or HIF-1 alpha plasma levels were most likely to have longer OS from the addition of E to G while patients with lower IL-8 levels had improved survival when treated with G alone, which may also be useful to stratify patient outcomes regardless of therapeutic intervention. Biomarker OS hazard ratio (95% CI) of low to high level (using median as cutpoint) G Alone G+E All T V T V T V IL-8 0.58 (0.39, 0.89) 0.51 (0.33, 0.74) 0.56 (0.37, 0.84) 0.51 (0.30, 0.86) 0.64 (0.48, 0.84) 0.62 (0.45, 0.85) CEA - - 0.59 (0.39, 0.90) 0.60 (0.37, 0.98) 0.67 (0.50, 0.89) 0.58 (0.43, 0.79) HIF-1 alpha - - 0.63 (0.43, 0.94) 0.59 (0.37, 0.95) 0.70 (0.54, 0.92) 0.58 (0.43, 0.79)
Estrogen receptor-positive (ER+) metastatic breast cancer (MBC) patients (pts) with extreme responses (ERs) to capecitabine having tumors with genomic alterations in DNA repair and chromatin remodeling genes.
Authors: Maren K. Levin, Kai Wang, Roman Yelensky, Ying Cao, Corinne Ramos, Glenn D. Hoke, John E. Pippen, Joanne Lorraine Blum, Barry Don Brooks, Gary A. Palmer, Norma Alonzo Palma, Sohail Balasubramanian, Jeffrey S. Ross, Joyce O'Shaughnessy
Journal: Journal of Clinical Oncology (2014)

555 Background: We sought to understand the genomic alterations in tumors of MBC pts who had extreme durations of response to capecitabine (C). Methods: Following IRB-approved informed consent, targeted next generation sequencing (NGS) was performed on pts’ FFPE primary breast cancer (n=4) or MBC (n=2) specimens at a CLIA-certified laboratory to characterize genomic alterations across 287 cancer-related genes. Reverse phase protein microarray (RPMA) was also performed. Results: Six postmenopausal pts with ER+/HER2- MBC and ERs with C were studied. Metastases comprised bone/lymph node (n=1) or liver (n=5; liver only, liver/bone, liver/bone/chest wall). Four pts had received ≥2 prior chemotherapy regimens for metastatic disease. Four pts received C + paclitaxel (mean 17 mos; range 4–57); three of these then continued C alone (mean 86 mos; range 59–118). Two pts received C monotherapy (54 and 91+ mos). C was discontinued after a mean of 66 mos in four pts (range 54–86); two pts remain on C (91+ and 122+ mos). On NGS, 50% (3/6) of pts’ tumors had likely functional alterations in DNA repair and chromatin remodeling genes (Table) – a higher than expected prevalence in ER+ MBC. Three pts had variants of unknown significance (VUS) in these pathways. PIK3CA substitutions or amplifications of AKT2, FGFR1, ZNF703, as well as phosphorylation of HER family receptors and their downstream proteins on RPMA did not appear to preclude ERs to C. Conclusions: Three MBC pts with ERs to C (54–122+ mos) had genomic alterations in DNA repair pathways (double strand break response and homologous recombination) and in histone acetyl- and methyltransferase genes. We are exploring the potential function of the VUS in the other three pts. Preclinical data show that sensitivity to 5-FU is enhanced by deficiencies in chromatin remodeling and homologous recombination genes (Matuo, et al. Genet Mol Res, 2013), suggesting a strategy for pt selection for C. Patient Genomic alterations or [VUS] DNA repair Chromatin remodeling 1 [BRCA2, FANCF] [SETD2] 2 CHEK2, PALB2 NCOR1, TET2 3 CHEK2 [BCORL1] 4 ATM EP300 5 [PARP1] [NCOR1, CBFβ] 6 [SETD2] [EP300, SETD2]
A randomized phase III trial of mFOLFOX6 plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment for metastatic colorectal cancer: West Japan Oncology Group study 4407G (WJOG4407G).
Authors: Kentaro Yamazaki, Michitaka Nagase, Hiroshi Tamagawa, Shinya Ueda, Takao Tamura, Kohei Murata, Takashi Tsuda, Eishi Baba, Masahiro Tsuda, Toshikazu Moriwaki, Taito Esaki, Yasushi Tsuji, Kei Muro, Koichi Taira, Tadamichi Denda, Takahiro Tsushima, Masahiko Ando, Satoshi Morita, Narikazu Boku, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2014)

3534 Background: FOLFIRI and FOLFOX showed equivalent efficacy for metastatic colorectal cancer (mCRC), however their combination with bevacizumab (Bev) have not been directly compared. Methods: The WJOG4407G study was a randomized, open-label, phase III trial. Patients (pts) with previously untreated mCRC were randomized to receive either mFOLFOX6+Bev (group A; oxaliplatin 85mg/m2, l-leucovorin 200mg/m2, bolus 5-FU 400mg/m2, infusional 5-FU 2,400mg/m2, and Bev 5mg/kg; q2w) or FOLFIRI+Bev (group B; irinotecan 150mg/m2instead of oxaliplatin), stratified by institution, adjuvant chemotherapy, and liver limited disease. The primary objective was to investigate non-inferiority of B to A in progression free survival (PFS) assessed in the full analysis population (all randomized pts without major violation of eligibility criteria); non-inferiority margin of hazard ratio (HR) 1.25 based on the assumption of median PFS 10/11 months in A/B (power 0.85, 1-sided alpha 0.025). The secondary endpoints were response rate, overall survival (OS), safety, and quality of life (QOL). Results: From September 2008 to January 2012, 395 (A/B 198/197) of 402 enrolled pts were eligible for efficacy analysis. Data cut-off date was July 2013. Median PFS in A/B were 10.7/12.0 months (HR 0.905, 95% CI 0.723-1.133; p=0.003 for non-inferiority and p=0.427 for superiority; events in 78% pts). There was no interaction effect between the treatment and KRAS(codon12, 13) mutation status. Subsequent treatments were performed in 168/157 pts after A/B. Median OS in A/B were 28.9/31.8 months (HR 0.901, 95% CI 0.683-1.189; events in 50% pts), and response rates were 62.2/63.8%. The common grade 3 or 4 adverse events in A/B were leukopenia 4.5/11.3%, neutropenia 35.4/45.6%, diarrhea 5.1/8.7%, febrile neutropenia 1.5/5.1%, peripheral neuropathy 21.7/0%, and venous thromboembolism 1.5/6.2%. The QOL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx were favorable for B throughout 18 months. Conclusions: FOLFIRI+Bev was non-inferior to mFOLFOX6+Bev with respect to PFS as 1st-line treatment for mCRC, and showed better trend in QOL. Clinical trial information: UMIN000001396.
Neoadjuvant chemotherapy (NCT) in 710 patients for operable breast cancer: Comparison of 2 pathological classifications
Authors: F. Penault-Llorca, C. Abrial, I. Raoelfils, S. Amat, M. Mouret-Reynier, M. Leheurteur, X. Durando, J. Dauplat, H. Curé, P. Chollet
Journal: Journal of Clinical Oncology (2006)

10502 Background: In a database harbouring the patients of several prospective phase II neoadjuvant trials (avcf, avcfm, fec 50–100, nem, net, tncf, taxotère/tncf, taxotere alone), clinical and pathological responses rates were studied in 710 women with stage II-III operable breast cancer treated 1982–2004. Pathological review was conducted to assess the residual disease in breast and nodes according to the 2 most used classifications in Europe: CHEVALLIER’s and SATALOFF’s (Am J Clin Oncol 1993; J Am Coll Surg 1995). Methods: Median age of the patients was 49.5 years [26–81]. Median diameter of the invasive tumour was 40 mm [10–130]. 555 (78%) patients had a canalar, 90 (13%) a lobular, 18 (2.5%) a mixed or invasive carcinoma, 36 (5%) neoplasic cells only and 11 (1.5%) another carcinoma. 25.6% of the tumours were grade III SBR, 28.3% grade 4 or 5 MSBR. The median number of NCT courses was 6 [1–9] followed by a surgery for 92%, a radiotherapy for 95%, an adjuvant chemotherapy (17%) and/or a hormonotherapy (52%). A breast evaluation was realized before, during and after NCT (Amat et al, Breast Cancer Res Treat 2005). Results: Intent to treat (n = 710), overall response rate was 68% (16% complete). The complete pathological response (pCR) rate was 14.18% according to Chevallier’s and 22.50% according to Sataloff’s classification. On 656 patients operated, 470 (72%) had a conservative surgery. On 520 patients with an axillary dissection, 272 (52.3%) had involved nodes (median number:1 [0–20]). After a median follow-up of 93 months, DFS and actuarial survival at 120 months were 54.9% and 66.5%, respectively.Chevallier’s classification level 1 (pCR in breast and axilla) was the most predictive of a good DFS, with a plateau appearance near 80%. Chevallier’s classification level 2 (in situ only) and Sataloff grade A (pCR and isolated tumor cells) yielded a lesser DFS (p &lt; 0.01). With a long follow-up, a complete pCR is the most favourable prognostic factor, followed by in situ only or isolated tumor cells, then residual tumor. Conclusions: Sataloff’s gives higher pCR figures than Chevallier’s without evidence of superior predictive value. The classification used is important to predict outcome after NCT. No significant financial relationships to disclose.
Role of surgery for gastric cancer with liver limited multiple metastases.
Authors: Hiromichi Shirasu, Takahiro Tsushima, Yutaka Tanizawa, Satoshi Hamauchi, Akiko Todaka, Tomoya Yokota, Nozomu Machida, Kentaro Yamazaki, Akira Fukutomi, Masanori Terashima, Katsuhiko Uesaka, Hirofumi Yasui
Journal: Journal of Clinical Oncology (2017)

170 Background: Although it has been suggested that surgery provides favorable outcome for gastric cancer (GC) patients (pts) with liver limited multiple metastases (LLM), the survival benefit of surgery comparing to systemic chemotherapy (CTx) has yet to be elucidated, especially in pts with LLM. The aim of this study was to explore the role of surgery for GC with LLM. Methods: We retrospectively reviewed the data of consecutive GC pts with LLM who underwent hepatectomy or received systemic CTx as initial therapy at Shizuoka Cancer Center between Dec. 2004 and Dec. 2015. Inclusion criteria were as follows: ECOG PS 0-1; histologically proven adenocarcinoma; synchronous or metachronous LLM; 2 or 3 LLM technically resectable disease; no prior CTx or radiotherapy Pts who were refractory to adjuvant CTx were excluded. Results: Nine of 24 pts who met the inclusion criteria underwent hepatectomy, and 15 pts received CTx. Pts’ background who received hepatectomy versus (vs) CTx was as follows: median age (range), 74 (64-81) vs 59 (42-76) years; male/female, 8/1 vs 14/1 pts; Histology intestinal/diffuse, 9/0 vs 10/5 pts; HER2 positive/negative/unknown 0/0/9 vs 2/5/8 pts; number of liver metastases 2/3, 9/0 vs 9/6; unilobar/bilobar, 5/4 vs 5/10 pts. In hepatectomy group, all 9 pts underwent radical hepatectomy (with gastrectomy for synchronous metastases), and 3 pts received adjuvant CTx. No in-hospital death or severe complication was observed. In CTx group, 11 pts received fluoropyrimidine plus cisplatin therapy, and trastuzumab was combined in 2 pts with HER2 positive tumor. Three pts underwent radical hepatectomy after CTx. Eight pts in hepatectomy group had recurrence. Recurrent sites were remnant liver (7), lymph node (1), and peritoneum (2). With median follow-up time of 47.9 months, median progression free survival was 8.0 months in hepatectomy group and 27.9 months in CTx group (p = 0.02). In CTx group, 3 pts who underwent subsequent radical hepatectomy after CTx had no recurrence or death. Median overall survival was 24.1 months in hepatectomy group and 38.4 months in CTx group (p = 0.15). Conclusions: Initial surgery for GC pts with LLM did not show survival benefit. But radical hepatectomy subsequent to CTx may associate with preferable outcome.
Novel Thrombogenic Biomarkers In Patients with Relapsed/Refractory Multiple Myeloma (MM) Treated with Lenalidomide (LEN) and Dexamethasone (Dex) Therapy
Authors: Kate Burbury, Peter C Gambell, Amanda Choo, Jennifer Curnow, Kevin Lynch, Simon J. Harrison, Hang Quach, David Ritchie, Miles Prince, David Alan A Westerman
Journal: Blood (2010)
Primary tumor location as a prognostic and predictive factor in metastatic colorectal cancer (mCRC) treated with chemotherapy plus cetuximab: A retrospective analysis.
Authors: Tamotsu Sagawa, Kyoko Hamaguchi, Akira Sakurada, Fumito Tamura, Tsuyoshi Hayashi, Koshi Fujikawa, Yasuo Takahashi, Yasushi Sato
Journal: Journal of Clinical Oncology (2017)

711 Background: Left- and right-sided colon cancers are significantly different in epidemiologic, clinicopathological and molecular characteristics. However, the impact of primary tumor location in mCRC treated biological targeted agent in combination with chemotherapy is unclear. We therefore investigated the prognostic and predictive impact of primary tumor location in mCRC. Methods: Single-institution, retrospective, case-control study was reviewed. A total of 96 patients with mCRC were enrolled between January 2011 and December 2015. We evaluated the association between tumor location and survival parameters in patients with previously untreated mCRC receiving first-line chemotherapy plus cetuximab or bevacizumab. The impact of primary tumor location for cetuximab and bevacizumab groups was analyzed, respectively. Left-sided primary tumors were defined as tumors from rectum to splenic flexure, while right-sided primary tumors were defined as tumors from cecum to the distal part of the transverse colon. Results: 68 patients presented left-sided tumors and 28 patients right-sided primary tumors. In the cetuximab group, left-sided tumors were significantly superior to right-sided tumors in terms of the progression-free survival (PFS) and Overall survival (OS) (PFS, left vs right, 18.3 vs 6.8 M, p = 0.0415; OS, 50.6 vs10.5 M, p = 0.0004). Likewise, in the bevacizumab group, OS showed differences between the left- and right-sided tumors (PFS, left vs right, 11.6 vs 7.3 M, p = 0.1904; OS, 25.7 vs 16.2 M, p = 0.0389). In left-sided tumors, cetuximab group were significantly superior to bevacizumab group in terms of the OS (PFS, cetuximab vs bevacizumab, 18.0 vs 11.6 M, p = 0.1088; OS, 50.6 vs 25.7 m p = 0.0354). Conversely, in right-sided, the survival times showed no differences between cetuximab- and bevacizumab group (PFS, cetuximab vs bevacizumab, 6.8 vs 7.3 M, p = 0.7816; OS, 10.5 vs 16.2 M, p = 0.1088). Conclusions: Our study demonstrates that primary tumor location is an important prognostic factor in previously untreated mCRC. Furthermore, left-sided primary tumor location might be a strong predictor of PFS and OS in cetuximab therapy.
A randomized phase II trial of two different four-drug combinations in advanced pancreatic adenocarcinoma: Cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel
Authors: S. Cereda, A. Rognone, M. Ghidini, S. Rezzonico, P. Passoni, E. Mazza, R. Nicoletti, A. Zerbi, E. Villa, M. Reni
Journal: Journal of Clinical Oncology (2009)

4614 Background: The combination of cisplatin (P), epirubicin (E), 5-fluorouracil (F) and gemcitabine (G) (PEFG regimen) yielded a progression-free survival at 6 months from treatment start (PFS6) of about 50% and a 1-year overall survival (OS) around 40% in patients with advanced pancreatic adenocarcinoma (PA). The current trial was aimed to assess whether the replacement of E with docetaxel (D) may improve PFS6. Methods: Chemo-naive patients with stage III or metastatic PA, age 18–75y, Karnofsky performance status (PS) &gt;50 received P (30 mg/m 2 day 1), G (800 mg/m 2 day 1) and capecitabine (1250 mg/m 2 /day days 1 to 14) and were randomized to receive either D at 25–30 mg/m 2 day 1 (arm A: PDXG regimen) or E at 30 mg/m 2 day 1 (arm B: PEXG regimen). Cycles were repeated every 14 days for a maximum of 6 months. Tumor was assessed by CT scan every 8 weeks. The Fleming design was used to calculate the sample size on the probability of being PFS6 (primary endpoint). Assuming P0=40% and P1=60%, α .05 and β.10, the study was to enroll 52 patients per arm. The regimen had to be considered of interest with &gt; 26 patients being PFS6. Results: Between July 2005 and September 2008, 105 patients were enrolled at a single institution, stratified by stage and randomized (53 arm A). Patients’ characteristics were (A/B): median age 61/59, PS &gt; 70 92/88%, metastatic disease 66/65%; CA19.9 &gt; upper limit of laboratory normal (ULN) 87/90%, median CA19.9 820/755 UI/mL. To date, 46 patients per arm are assessable for the primary endpoint: PFS6 was 58/54%. One- year OS was 41% in both arms. A partial response was observed in 61/37% of patients. Among assessable patients with basal CA19.9 value &gt; ULN (37 per arm), a major biochemical response (reduction &gt;89%) was observed in 46/35% and a minor biochemical response (reduction between 50 and 89%) in 43/35% of patients. Main per cycle G3–4 toxicity was: neutropenia 4/13%, thrombocytopenia 3/2%, anemia 4/3%, fatigue 6/4%. Conclusions: PEXG yielded similar results when compared to prior series treated by PEFG, suggesting that capecitabine may replace F. The inclusion of D instead of E seems to be promising. The present trial confirms the relevant impact on outcome of advanced PA of four-drug regimens. No significant financial relationships to disclose.