bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, safety, and immune activation with pegylated human IL-10 (AM0010) plus FOLFOX in metastatic pancreatic adenocarcinoma (PDAC).
Authors: Hecht J. Randolph , Falchook Gerald Steven , Patel Manish R. , Aljumaily Raid , Infante Jeffrey R. , Naing Aung , Wong Deborah Jean Lee , Autio Karen A. , Ratti Navneet , Wainberg Zev A. , Bendell Johanna C. , Pant Shubham , Brown Gail Linda , Van Vlasselaer Peter , Oft Martin , Papadopoulos Kyriakos P. 
Published: September 2018

4111 Background: Oxaliplatin or nal-irinotecan plus 5-FU are used as 2nd-line PDAC therapy (mOS 5-6 months (m)). PDAC also has been largely refractory to immune therapies which may depend on the expansion of activated, intratumoral, tumor specific cytotoxic CD8+ T cells that are low in most PDACs. AM0010 stimulates survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Immune activation, durable stable disease and a 1yr survival of 22.5% was seen in salvage PDAC patients (pts) receiving AM0010 alone. Platins or 5-FU may activate immune responses to cancer and AM0010 has shown synergistic anti-tumor results with FOLFOX in preclinical models. In this phase 1b clinical study, the safety and efficacy of AM0010 +FOLFOX was studied in PDAC pts. Methods: PDAC pts progressing on a median of 1 prior therapy (range 1-3) were treated with AM0010 (5ug/kg SQ, qd) + FOLFOX (n = 21), an additional 4 pts with prior oxaliplatin and 5-FU were included in the safety population (n = 25). Tumor responses were assessed using irRC. Serum cytokines, activation of blood derived T cells and peripheral T cell clonality were analyzed. Pretreatment archival tissue samples were evaluated by IHC for tumor infiltration by CD8+ T cells. Results: On AM0010 + FOLFOX, G3/4 TrAEs included thrombocytopenia (52%), anemia (36%) and neutropenia (36%). A modified AM0010 dose schedule (5 days on 2 days off) avoided G3/4 thrombocytopenia. As of 01/31/2017, 2 patients remained on treatment for > 1 year. 19 pts had objective tumor response assessment; 2 had irCR, 1 irPR, 11 irSD. ORR is 15.8%, DCR is 73.7%. With median follow-up of 11.0 m (range 5.8-16.3), mPFS was 3.5 m and mOS 10.0 m. Pts with more intra-tumoral CD8+ T cells had longer OS. AM0010 + FOLFOX increased serum Th1 cytokines and reduced mediators of chronic inflammation and TGFb. AM0010 induced de-novo oligoclonal expansion of T cell clones in patients with prolonged survival. Conclusions: AM0010 plus FOLFOX is well tolerated in patients with PDAC. The observed immune activation including clonal T cell expansion and prolonged objective tumor responses are encouraging in this advanced PDAC population. This regimen is currently being studied in a phase 3 trial. Clinical trial information: NCT02009449.
Adjuvant chemotherapy and outcome in patients (pts) with nodal (N-) and resection margin negative (R0) pancreatic adenocarcinoma (PC): A systematic review and meta-analysis.
Authors: Flaum Nicola , Hubner Richard , Valle Juan W. , Amir Eitan , McNamara Mairead G 
Published: September 2018

4114 Background: Adjuvant chemotherapy following PC resection improves overall survival (OS). It is uncertain whether benefit is influenced by nodal and resection status or other factors. Methods: A systematic review of electronic databases identified published phase 2/3 studies investigating use of adjuvant chemotherapy in pts with resected PC. Efficacy (disease-free survival [DFS], OS, 5 yr OS) was explored using meta-analysis. Subgroup analysis explored effects based on nodal/resection status. Meta-regression also explored influence of age, gender, performance status [PS] and proportion of pts with head of pancreas (HOP) tumors on benefit of adjuvant chemotherapy. Results: Ten studies comprising 3644 pts were included. Two prospective phase 2 studies; 8 phase 3 trials. Median age was 63 yrs (range 24-84), 46% male. In 2268 pts with PS reported; 42% were PS 0, 51% PS 1. Tumor location was reported in 719 pts; 82% had HOP tumors. Of 3524 pts with available data; 33% N- and 67% R0. Overall, in studies of experimental vs control, adjuvant therapy significantly improved DFS (HR 0.67, CI 0.48-0.93, P = 0.02), OS (HR 0.77, 95% CI 0.68-0.87, P < 0.001) and odds of death risk at 5 yrs (OR 0.53, 95% CI 0.41-0.70, P < 0.001). In studies comparing chemotherapy to surgery only, adjuvant therapy also significantly improved DFS (HR 0.57, 95% CI 0.49-0.76, P < 0.001) and OS (HR 0.74, 95% CI 0.64-0.87, P < 0.001). There was a numerical but non-significant greater effect of adjuvant therapy in N- vs N+ pts (HR 0.58 vs 0.71, P for difference = 0.29). There was no difference in effect between pts with R0 or R1 disease (HR 0.70 vs 0.69, P for difference = 0.95). There was greater OS benefit from adjuvant therapy in pts with PS 0 (P = 0.04) and significantly less benefit on 5 yr OS in pts with HOP tumors (P = 0.04). Conclusions: The relative benefit of adjuvant chemotherapy seems similar in N-/N+ and in R0/R1 pts. This will translate into greater absolute benefit in the N+ and R1 pts due to their greater absolute risk of recurrence/death. Adjuvant chemotherapy is recommended for all pts with resected PC, where clinically appropriate, and greater benefit was seen in pts with PS 0 and body/tail tumors.
Effect of inflammatory and nutritional (IN) status on induction chemotherapy (CT) followed by chemoradiotherapy (CRT) for locally advanced pancreatic cancer (LAPC): An exploratory subgroup analysis of JCOG1106.
Authors: Mizuno Nobumasa , Fukutomi Akira , Mizusawa Junki , Katayama Hiroshi , Nakamura Satoaki , Ito Yoshinori , Hiraoka Nobuyoshi , Ioka Tatsuya , Ueno Makoto , Ikeda Masafumi , Sugimori Kazuya , Shimizu Kyoko , Okusaka Takuji , Ozaka Masato , Yanagimoto Hiroaki , Nakamori Shoji , Azuma Takeshi , Hosokawa Ayumu , Ishii Hiroshi , Furuse Junji ,   Japan Clinical Oncology Group (JCOG)
Published: September 2018

4123 Background: JCOG1106 is a randomized selection phase 2 trial to evaluate the efficacy and safety of CRT (S-1 concurrent RT) with (Arm B) or without (Arm A) induction CT of gemcitabine (GEM) for LAPC. In the final analysis, we selected Arm A as a promising regimen due to a poorer 2-year overall survival (OS) of Arm B, in spite of a favorable 1-year OS with crossing of the survival curves around 1-year (Ioka, ESMO2016). Therefore, this study aimed to explore subgroups benefit more from either treatment. IN statuses defined by such as serum C-reactive protein (CRP) and serum albumin (Alb) are recognized as prognostic and predictive factors in patients (pts) with various cancers receiving CT or CRT. We hypothesized that IN status may modify the effect of induction CT. Methods: Subjects were all eligible pts who were enrolled in JCOG1106 (n = 51/49 in Arm A/B). Glasgow Prognostic Score (GPS) was classified by baseline CRP and Alb. Pts with a CRP ≤ 10 mg/L and Alb ≥ 35 g/L were allocated to GPS 0, with a CRP > 10 mg/L or Alb < 35 g/L to GPS 1, and with a CRP > 10 mg/L and Alb < 35 g/L to GPS 2. This exploratory subgroup analysis was performed by Cox regression analysis to investigate the impact of IN status at baseline on OS. Less than 0.1 of P-value for interaction was regarded as significant. Results: GPS, CRP and Alb showed significant treatment interactions in terms of OS. HRs of Arm B to Arm A were 1.35 (0.82–2.23) and 0.59 (0.24–1.50) in the GPS 0 (n = 44/34 in Arm A/B) and GPS 1/2 group (n = 7/15) ( P-interaction = 0.06). HRs were 2.57 (1.36–4.86) and 0.70 (0.37–1.32) in the low CRP group (≤ 1.35 mg/L, n = 25/25) and high CRP ( > 1.35 mg/L, n = 26/24) ( P= 0.01). HRs were 1.62 (0.77–3.40), 2.70 (1.17–6.23) and 0.52 (0.24–1.13) in the 1st (≤ 0.7 mg/L, n = 16/16), 2nd ( > 0.7, ≤ 3.0 mg/L, n = 20/16), and 3rd tertiary CRP group ( > 3.0 mg/L, n = 15/17) ( P= 0.01). HRs were 2.29 (1.11–4.69) and 0.89 (0.51–1.54) in the high Alb group ( > 40 g/L, n = 23/17) and low Alb (≤ 40 g/L, n = 28/32) ( P= 0.04). Arm B showed better survival in subgroups of GPS 1/2, higher CRP or lower Alb compared to Arm A. Conclusions: Pts with poor IN status may have treatment benefit of induction CT followed by CRT for LAPC. Clinical trial information: UMIN000006811.
Phase III trial of adjuvant sunitinib in patients with high-risk renal cell carcinoma (RCC): Validation of the 16-gene Recurrence Score in stage III patients.
Authors: Escudier Bernard J. , Rini Brian I. , Martini Jean-Francois , Chang Wayne Yen-Hwa , Breza Jan , Magheli Ahmed , Svedman Christer , Lopatin Margarita , Knezevic Dejan , Goddard Audrey D. , English Patricia A , Li Rachel , Lin Xun , Valota Olga , Cartenì Giacomo , Staehler Michael D. , Motzer Robert J. , Ravaud Alain 
Published: September 2018

4508 Background: Adjuvant therapy with sunitinib (SU) compared with placebo (PBO) prolonged disease-free survival (DFS) in 615 patients (pts) with high-risk RCC (hazard ratio [HR] 0.76; P= 0.03) in the S-TRAC trial. The 16-gene Recurrence Score (RS) was developed and validated to predict risk of recurrence of RCC after nephrectomy in 2 cohorts of stage I–III pts (Rini et al., Lancet Oncol 2015;16:676-85). We present further validation of RS results in high-risk stage III pts from S-TRAC. Methods: The study was prospectively designed with prespecified genes, algorithm, endpoints, analytical methods, and analysis plan using primary RCC tissues from 212 evaluable pts with informed consent. Gene expression was quantitated by RT-PCR; primary analysis focused on stage III (n = 193 pts). Time to recurrence (TTR) and DFS were analyzed using Cox proportional hazard regression. Results: Baseline characteristics were similar in SU and PBO arms and in pts with and without gene expression data; effect of SU was numerically similar to that in the entire trial (DFS HR 0.78, 95% CI 0.48–1.24; P= 0.29). RS predicted TTR and DFS in both treatment arms with the strongest results observed in PBO arm where high RS group had significantly higher risk (Table). Interaction of RS with treatment was not significant (TTR P= 0.192; DFS P= 0.219); however, the number of events was relatively low. Conclusions: The prognostic value of the 16-gene assay was confirmed in S-TRAC. RS is now validated with consistent results in 2 separate studies (level IB evidence). RS results may help identify patients at high risk who could derive higher absolute benefit from adjuvant treatment. The predictive value of RS to select patients for adjuvant SU requires further investigation in independent adjuvant trials. [Table: see text]
Mismatch repair (MMR) detection in urothelial carcinoma (UC) and correlation with immune checkpoint blockade (ICB) response.
Authors: Iyer Gopa , Audenet Francois , Middha Sumit , Carlo Maria Isabel , Regazzi Ashley Marie , Funt Samuel , Al-Ahmadie Hikmat , Solit David B. , Rosenberg Jonathan E. , Bajorin Dean F. 
Published: September 2018

4511 Background: High mutation burden correlates with response to ICB in UC. Loss of function alterations or epigenetic silencing of MMR genes results in MMR deficient (MMR-D) UC, leading to a microsatellite instability (MSI) mutation signature. We used a CLIA-certified pipeline (MSISensor) to interrogate Next Generation sequencing (NGS) data from UC tumors to identify MMR-D patients (pts). We correlated MMR-D with mutation load and response to ICB. Methods: 447 tumors from 424 UC pts underwent prospective NGS using the MSK-IMPACT exon capture assay and genomic interrogation of microsatellite (MS) sites using MSIsensor, which assesses the number/length of MS within the targeted regions of tumor-normal sample pairs. Loci are considered unstable (somatic) if k-mer distributions are significantly different between tumor and matched normal using a standard multiple testing correction of χ2 p-values. The fraction of unstable sites is reported as an MSIsensor score. MSI high tumors have scores >10 while <3 are denoted MS stable. Scores from 3-10 were categorized as MS intermediate. Results: Thirteen pts (3%) had an MSI score >10 and a median mutation count of 52 (36.5-73.5) vs 8 (5-13) in 410 non-MMR-D pts (p<0.01). Ten pts (71%) had upper tract UC. Of 9 pts with germline sequencing performed, 8 (89%) had heritable loss of function mutations in MMR proteins (Lynch syndrome, LS). One pt had a somatic MSH2 mutation. Fifteen pts had MS scores from 3-10: 3 had LS, one a BRCA1 germline alteration, and 9 did not have germline testing available. Two pts with MSI scores <3 had extremely high mutation loads (213 and 414) and both had POLE mutations. Five pts received ICB therapy for metastatic and all achieved near-complete or complete responses. No MMR-D pt has died at 27 months follow-up vs 125 non-MMR-D pts (p=0.014). Conclusions: The MSI Sensor assay can discriminate MSI high from MMR proficient UC. While rare, MMR-D UC is characterized by a high mutation load, strong association with Lynch syndrome, and durable responses to ICB, similar to data in colon cancer. An MMR-D signature should trigger genetic testing for Lynch syndrome. ICB should be considered early in the treatment course of patients with MMR-D metastatic UC.
FDG PET scan (PET) positive residual lesions after chemotherapy (chemo) for metastatic seminoma: Results of an International Global Germ Cell Cancer Group (G3) registry.
Authors: Cathomas Richard , Klingbiel Dirk , Bernard Brandon David , Lorch Anja , Garcia del Muro Xavier , Morelli Franco , De Giorgi Ugo , Fedyanin Mikhail , Oing Christoph , Haugnes Hege Sagstuen , Hentrich Marcus , Fankhauser Christian Daniel , Goncalves Margarida Brito , Cohn-Cedermark Gabriella Elisabeth , Daugaard Gedske , Fornarini Giuseppe , Aurilio Gaetano , Mayer Frank , Huss Katharina , Beyer Joerg 
Published: September 2018

4521 Background: Residual disease is a frequent finding after chemo for metastatic seminoma. Watchful waiting is recommended for residual lesions < 3 cm or lesions ≥3 cm with negative PET. Data on the optimal management of PET positive residual lesions is lacking. Methods: A retrospective analysis within the G3 Group identified 91 patients (pts) from 9 countries with metastatic seminoma and residual PET positive lesions after chemo. Pts with elevated AFP ( > 2xULN) or non-seminomatous components at diagnosis were excluded. We analyzed the post PET management chosen and its impact on relapse and survival. Results: Median follow-up was 29 (IQR 10 – 64) months. Median age at diagnosis was 41 (range 19 – 69) years. The primary tumor was gonadal in 68 pts (76%), retroperitoneal in 12 pts (13%) and mediastinal in 10 pts (11%). Prior to chemo the median size of the largest metastasis was 10 (range 1.4 – 23) cm, 67 pts (74%) had elevated LDH and 51 pts (57%) elevated HCG. Median diameter of the largest residual mass was 4.8 (range 1.1 – 14) cm mainly located in the retroperitoneum (77%), pelvis (15%), mediastinum (16%) or lung (4%). Median time from last day of chemo to PET was 7 (IQR 4 – 10) weeks. Post PET management was repeated imaging in 46 pts (51%), resection in 32 pts (35%), biopsy in 9 pts (10%) and radiotherapy in 4 pts (4%). Histology of the resected specimen was necrosis only in 25 (78%) and vital seminoma in 7 cases (22%). No biopsy revealed vital seminoma. Relapses occurred after a median of 3.7 (IQR 2.5 – 4.9) months in 16 pts (18%): 2/9 (22%) after biopsy, 12/46 (26%) on repeated imaging and 2/32 (6%) after resection (one necrosis, one < 10% vital seminoma). Site of relapse was the area of residual disease in 14 pts (88%) and additional distant relapse (one bone, one lung) in 2 pts (12%). All relapsed pts received successful salvage chemo apart from one who died from treatment and two pts who are alive with ongoing treatment. Conclusions: PET positive post chemo residual lesions in seminoma pts are false positive in about 75%. Relapses in PET positive pts occur early and can be salvaged with chemo. Further analysis is needed to identify risk factors for relapse.
Updated efficacy and tolerability of durvalumab in locally advanced or metastatic urothelial carcinoma (UC).
Authors: Hahn Noah M. , Powles Thomas , Massard Christophe , Arkenau Hendrik-Tobias , Friedlander Terence W. , Hoimes Christopher J. , Lee Jae-Lyun , Ong Michael , Sridhar Srikala S. , Vogelzang Nicholas J. , Fishman Mayer N. , Zhang Jingsong , Srinivas Sandy , Parikh Jigar , Antal Joyce , Jin Xiaoping , Ben Yong , Gupta Ashok Kumar , O'Donnell Peter H. 
Published: September 2018

4525 Background: Anti-PD-L1 immunotherapy shows promising clinical activity in UC. We report a planned update of the safety and efficacy of durvalumab in patients (pts) with locally advanced/metastatic UC from a multicenter, phase 1/2 open-label study. Methods: Pts received durvalumab 10 mg/kg every 2 weeks (Q2W) up to 12 months (mo) or until unacceptable toxicity, progression, or starting another anticancer therapy. Primary endpoints were safety and confirmed objective response rate (ORR) by blinded independent central review (RECIST v1.1). Duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were key secondary endpoints. Tumor PD-L1 expression was assessed by Ventana SP263 assay (PD-L1 high = ≥25% PD-L1 expression on tumor or immune cells). Results: As of Oct 24, 2016 (data cutoff [DCO]), 191 pts had received treatment. Median follow-up was 5.78 mo (range, 0.4–25.9). All pts had Stage 4 disease and 99.5% had prior anticancer therapy (95.3% post-platinum). As of DCO, ORR was 17.8% (34/191), including 7 CRs, with responses observed regardless of PD-L1 status (Table). Responses occurred early (median time to response, 1.41 mo) and were durable (median DoR not reached [NR]). Median PFS and OS were 1.5 mo (95% CI, 1.4, 1.9) and 18.2 mo (95% CI, 8.1, not estimable [NE]), respectively; the 1-year OS rate was 55.0% (95% CI, 43.9%, 64.7%). Grade 3/4 treatment-related AEs occurred in 6.8% of pts; grade 3/4 immune-mediated (im)AEs occurred in 4 pts; 2 pts discontinued due to imAEs (acute kidney injury and autoimmune hepatitis). Conclusions: Durvalumab 10 mg/kg Q2W shows favorable clinical activity and an excellent safety profile in locally advanced/metastatic UC pts. Table. Antitumor activity in UC pts, including second-line or greater (≥2L) post-platinum pts Clinical trial information: NCT01693562. [Table: see text]
Safety and efficacy of docetaxel + b-701, a selective inhibitor of FGFR3, in subjects with advanced or metastatic urothelial carcinoma.
Authors: Bellmunt Joaquim , Pal Sumanta K. , Picus Joel , Kohli Manish , Arriaga Yull Edwin , Milowsky Matthew I. , Holash Jocelyn , Ramies David Albert , McGreivy Jesse S. 
Published: September 2018

4540 Background: Patients w/ locally advanced or metastatic urothelial carcinoma (UCC) have a poor prognosis. Prior to atezolizumab’s approval, there were no approved treatments (txs) for pts who progressed after chemotherapy. Even w/ immune checkpoint inhibitors, most pts require additional txs. FGFR3 is frequently overexpressed in UCC and 15-20% of pts w/ advanced disease have tumors w/ FGFR3 gene mutations or fusions. B-701 (formerly R3Mab) is a fully human monoclonal antibody against FGFR3 that blocks activation of the wildtype and genetically activated receptor. NCT02401542 is a phase (ph) 1b/2 study designed to evaluate the safety and efficacy of B-701 plus docetaxel (D) in advanced UCC pts. Methods: The study has a lead-in (n=20 pts) and a randomized ph (n=201). Eligible pts: Stage IV UCC, relapsed/refractory to 1 or 2 prior chemotherapy regimens not including taxanes with ECOG 0-1. Txs: B-701 at 25 mg/kg q3w (+ loading dose on C1D8) and D at 75 mg/m2 q3w. Efficacy assessed by RECIST 1.1. Primary obj: PFS and safety. Secondary obj: overall response rate (ORR); duration of response (DOR); disease control rate (DCR); overall survival (OS). Exploratory obj: association of FGFR3 status w/ efficacy and AEs. Results: As of 20 Jan 2017, 19 pts enrolled to lead-in ph w/median age 66 yrs, ECOG 1 58%, Hgb <10 gm/dL 5%, liver mets 26% and ≥ 2 prior regimens 63%. 17 evaluable for PFS/ORR. 5 pts w/ FGFR3 mut or TACC3-fus. Gr ≥3 AEs occurring in ≥2 pts: decreased neutrophils (26.3%), neutropenia (10.5%), decreased WBCs (10.5%). 2 pts had D dose reductions and 1 pt discontinued tx due to AE (disseminated intravascular coagulation). Conclusions: Preliminary results show that B-701 combines safely and effectively with D in UCC, with the combination being well tolerated and showing promising ORR and PFS in pts w/ FGFR3 mut/fus. The protocol has been amended to add Cohorts 2 (B-701+D) and 3 (B-701) (n=20 pts/cohort) for pts w/ FGFR3 mut/fus+ tumors only. Clinical trial information: NCT02401542. [Table: see text]
Prognostic role of circulating tumor cells-CTCs in metastatic renal cell carcinoma.
Authors: Basso Umberto , Facchinetti Antonella , Rossi Elisabetta , Maruzzo Marco , Conteduca Vincenza , Aieta Michele , Massari Francesco , Fraccon Anna Paola , Mucciarini Claudia , Sava Teodoro , Santoni Matteo , Pegoraro Maria Cristina , Durante Emilia , Nicodemo Maurizio , Perin Alessandra , Bearz Alessandra , Pasini Felice , Gatti Carlo , Zamarchi Rita , Zagonel Vittorina ,   CTC in mRCC Investigator Group
Published: September 2018

4568 Background: CTCs can be isolated in peripheral blood of cancer pts and have demonstrated to have prognostic role in several metastatic tumors such as breast, colorectal and prostate cancer. Few data are available for Renal Cell Carcinoma-RCC. Methods: We designed a multicenter prospective observational trial aiming to assess the association between CTC counts and PFS of RCC pts treated with an antiangiogenic tyrosine-kinase inhibitors as a first-line regimen for metastatic disease. OS and response rate were secondary objectives. Both basal and sequential counts were enumerated by Cellsearch system at 4 time points: day 0 of treatment, +1 mo, +3 mo, at progression or 12 mo in the absence of progression. Ethics Committee approval was obtained. Results: Among 246 pts, 195 are eligible for the present analysis, 71.4% males, median age 69 yrs (range, 27 to 91), 81% with previous partial/total nephrectomy. Treatment was sunitinib (77.5%), pazopanib (21%) or sorafenib (1.5%). According to Heng criteria there were 24.6% good, 62.6% intermediate and 24.6% poor prognosis pts. After a median follow-up of 31.5 mo, median PFS is 13.6 mo (23% censored), 49.2% of pts are still alive. Investigator-assessed best response was 3.8% complete, 37.3% partial response, 33% stable, 25.9% progression. At baseline 91 pts had 1 or more CTCs, median 2, range 1 to 263. Pts with at least 1 CTC had a significantly shorter PFS compared to negative pts (8.8 vs 16.6 mo, p = 0.03), HR = 1.41 (95%CI 1.02-1.9). Thirty pts had > = 3 CTCs, with a median PFS of 5.8 vs 15 mo in the remaining pts (p = 0.002), HR = 1.99 (CI 1.28-3.03). Percentage of pts with > = 3 CTCs increased from 6.6% of good, 18.4% intermediate and 38.9% poor Heng score pts (p = 0.042). Pts with > = 3 CTCs had a shorter estimated OS of 13.8 mo vs 52.8 mo (p = 0.003), HR = 1.99 (CI 1,17-3.2). Correlation between CTC positivity and response rate was not significant. Conclusions: In this robust multicenter prospective cohort of first-line metastatic RCC pts, the presence of 3 or more CTCs predicts a significantly shorter PFS and OS. Further analyses are ongoing on apoptotic markers of CTCs and concomitant counts of endothelial cells collected in the same cohort.