bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating free DNA as a prognostic biomarker in patients with advanced ALK+ NSCLC treated with alectinib from the global phase III ALEX trial.
Authors: Dziadziuszko Rafal , Peters Solange , Mok Tony S. K. , Camidge D. Ross , Noé Johannes , Nowicka Malgorzata , Bordogna Walter , Morcos Peter N. , Smoljanovic Vlatka , Shaw Alice Tsang 
Published: March 2020

9053 Background: Circulating free DNA (cfDNA) released predominantly by tumors into the blood correlates with tumor load, but correlation with outcomes after ALK inhibitor treatment is poorly understood. Here, we examine the prognostic potential of cfDNA in the phase III ALEX trial of alectinib versus crizotinib in previously untreated patients with advanced ALK+ NSCLC. Methods: Data cutoff was December 1, 2017. Median cfDNA was determined from 276 baseline samples; patients were stratified into ‘≤median’ and ‘ > median’ biomarker-evaluable populations (BEP). Results: Median cfDNA was 11.5ng/mL. Baseline characteristics were mostly balanced between the crizotinib (≤median, n = 72; > median, n = 67) and alectinib (≤median, n = 66; > median n = 71) BEPs. However, the alectinib > median BEP had more active smokers (7.0% vs crizotinib 1.5%), more measurable/non-measurable CNS lesions (47.9% vs 41.8%) and more patients with TP53 short-variant (SV) (44.8% vs 32.8%); the alectinib ≤median BEP had more active smokers (7.6% vs crizotinib 2.8%). Alectinib exposure was not substantially different between relevant BEPs. Higher cfDNA amount was associated with measurable/non-measurable CNS lesions and TP53 SV. Tumor burden positively correlated with normalized cfDNA amount (Pearson correlation 0.204; p < 0.001). Median PFS by investigator in the ≤median BEP was 34.9 months alectinib vs 14.8 crizotinib (HR 0.37, 95% CI 0.22–0.61, p < 0.0001); in the > median BEP it was 14.8 months alectinib vs 8.6 crizotinib (HR 0.43, 95% CI 0.28–0.64, p < 0.0001). Response rates in the ≤median BEP were 82.3% alectinib vs 70.4% crizotinib; in the > median BEP, 70.2% alectinib vs 55.4% crizotinib. Median duration of response in the ≤median BEP was not reached for alectinib vs 21.0 months for crizotinib; in the > median BEP, 33.1 months alectinib vs 7.3 crizotinib. Conclusions: Tumor burden positively correlated with cfDNA amount; patients with ≤median cfDNA at baseline had better prognosis than those with > median cfDNA. Alectinib consistently improved PFS, DOR and ORR versus crizotinib across BEPs, reducing the risk of tumor progression by > 50% compared with crizotinib. Clinical trial information: NCT02075840.
First subsequent treatment after discontinuation of durvalumab in unresectable, stage III NSCLC patients from PACIFIC.
Authors: Planchard David , Cho Byoung Chul , Gray Jhanelle Elaine , Paz-Ares Luis G. , Ozguroglu Mustafa , Villegas Augusto E. , Daniel Davey B. , Vicente David , Murakami Shuji , Hui Rina , Kurata Takayasu , Chiappori Alberto , Lee Ki Hyeong , De Wit Maike , Gu Yu , Wadsworth Catherine , Dennis Phillip A. , Antonia Scott Joseph 
Published: March 2020

9054 Background: In the phase 3 PACIFIC trial of unresectable, stage III NSCLC patients (pts) without progression after concurrent chemoradiotherapy (cCRT), durvalumab (durva) significantly improved PFS and OS with similar safety compared to placebo (pbo). We performed exploratory analyses to characterize first subsequent treatment (Tx) after discontinuation of durva. Methods: Pts with WHO PS 0/1 and any tumor PD-L1 status were randomized (2:1) 1–42 days after ≥2 cycles of platinum-based cCRT to durva 10 mg/kg IV or pbo Q2W up to 12 months, stratified by age, sex and smoking history. Pts were classified by the use or not of first subsequent Tx and category of first systemic Tx (platinum doublet CT [PDCT], single-agent CT [SCT], immunotherapy [IT] or targeted therapy [TT]). Results: As of Mar 22, 2018, 216/476 (45.4%) and 153/237 (64.6%) in the durva and pbo arms, respectively, had a RECIST-based PFS event per BICR (5.7% and 8.4% due to death). 195 (41.0%) and 128 (54.0%) received first subsequent Tx, most of which were systemic Tx (158 [33.2%] and 109 [46.0%]): PDCT (16.4% and 19.0%), SCT (8.6% and 8.4%), IT (4.2% and 13.5%) or TT (3.8% and 5.1%); 7.8% and 8.0% received RT only. Time to first subsequent therapy or death (TFST) was longer with durva vs pbo (HR 0.58; 95% CI 0.47–0.72; median 21.0 vs 10.4 months). Baseline characteristics of pts with or without first subsequent Tx were similar, and similar across durva or pbo arms. Among pts with systemic Tx, baseline characteristics (including pre-cCRT PD-L1 status) were generally similar, except pts on TT, more of whom were EGFR+ (70.0% vs 0–6.6% of other systemic Tx groups) with commonly associated phenotypes (more females, Asians, non-smokers and non-squamous pts). Best overall response to first systemic Tx will be presented. Conclusions: Due to longer PFS and fewer progression events with durva vs pbo, fewer pts on durva required subsequent Tx and, per TFST, much later. With the exception of IT, use of each subsequent Tx was similar between the durva and pbo arms with PDCT the most common. Baseline characteristics were similar for pts with or without first subsequent Tx and pts who received first systemic Tx, except for pts who received TT, as expected due to their molecular profile.
Real-world practice patterns and impact of PD-L1 expression testing in patients with advanced non-small cell lung cancer.
Authors: Leapman Michael , Presley Carolyn J , Zhu Weiwei , Soulos Pamela R. , Adelson Kerin B. , Boffa Daniel J. , Gross Cary Philip 
Published: March 2020

9059 Background: Several tests measuring programmed cell death ligand 1 (PD-L1) expression are available to select patients with advanced non-small cell lung cancer (aNSCLC) for PD-1 axis therapy including FDA approved companion diagnostics (CoDx), as well as complementary (CyDx) and laboratory developed tests (LDTs). However, it is unknown how rapidly PD-L1 expression testing has become adopted, which type of tests are used, or whether testing affects first-line therapy. Methods: We retrospectively reviewed the Flatiron Health electronic health record-derived database, reflecting real-world care at community oncology practices in the U.S. We evaluated trends in the use of PD-L1 expression testing within 12 months of diagnosis. Among patients diagnosed after FDA approval of PD-L1 testing prior to first-line therapy (Oct 2016), and without other identifiable driver mutations, we used multivariable logistic regression to examine the association between PD-L1 testing and receipt of first-line PD-1 axis therapy. We further examined the association between PD-L1 expression result (using overall reported status or % staining) and choice of first-line therapy. Results: We identified 49,546 patients with aNSCLC from 2011 through the third quarter of 2018. The use of PD-L1 expression testing increased from 7.0% in 2015 to 70.6% in 2017 (p < 0.01). Among those receiving testing, the proportion of patients receiving CoDx increased from 29.9% in 2015 to 73.0% in 2017 with corresponding reductions in CyDx and LDTs. PD-L1 expression testing was associated with use of PD1-axis therapy in the first-line (OR = 2.92, 95% CI 2.59-3.30). Among 4,942 treated patients diagnosed after Oct 2016, those with ≥50% staining more frequently received first line PD-1 axis therapy (82.9%) than those with intermediate (35.5%) or low (25.8%) positive staining; conversely, patients with ≥50% were less likely to receive chemotherapy alone or combination with PD-1 axis therapy. Conclusions: PD-L1 expression testing was rapidly adopted following FDA approval of companion diagnostic testing for aNSCLC. Although the results of PD-L1 expression testing inform the choice of first-line therapy, a substantial proportion of patients are not tested prior to first line treatment.
Therapeutic and prognostic impacts of specific gene alterations for squamous cell lung cancer: A result of nationwide genome screening in Japan (LC-SCRUM-Japan).
Authors: Kato Terufumi , Matsumoto Shingo , Umemura Shigeki , Yoh Kiyotaka , Nishino Kazumi , Daga Haruko , Tsubata Yukari , Ebi Noriyuki , Miyamoto Shingo , Shingyoji Masato , Hashimoto Shigeki , Nakagawa Taku , Hara Satoshi , Goto Koichi 
Published: March 2020

9060 Background: Various gene alterations occur during the development of squamous cell lung cancer (SqLC), but specific gene alterations for SqLC and their clinical significance remain unknown. Methods: In a nationwide genome screening project (LC-SCRUM-Japan), we have prospectively analyzed lung cancer patients for genetic alterations using a next-generation sequencing (NGS) system, Oncomine Comprehensive Assay, and have established a large-scale clinico-genomic database. Results: Since February 2013 to December 2018, a total of 6692 lung cancer patients (686 SqLCs, 5360 non-squamous non-small cell lung cancers [Non-sq] and 646 small cell lung cancers [SCLCs]) had been enrolled in the LC-SCRUM-Japan. The success rate of the NGS assay was 91%. Of 639 SqLCs analyzed, 274 (48%) had potentially targetable gene alterations, including 77 NFE2L2 (encoding NRF2) mut, 50 PIK3CA mut, 46 FGFR1 amp, 40 EGFRmut/amp, 36 PTEN mut, 23 KRAS mut, 6 AKT1 mut, 6 MET ex14skip, 5 ALK fusions, 2 FGFR3 fusions. Among the alterations detected, NFE2L2 mut and FGFR1 amp were significantly frequent in SqLC than Non-sq or SCLC (NFE2L2, 12.1% vs. 1.0% vs. 1.3%; p < 0.001, and FGFR1, 7.2% vs. 1.1% vs. 3.4%; p < 0.001). In advanced SqLC patients who received platinum-containing chemotherapies, the median progression-free survival (mPFS) was significantly shorter in NFE2L2-mutated patients (NRF2-type) than NFE2L2/FGFR1-negative patients (nonNF-type) (3.8 [95%CI, 2.9-5.1] vs. 4.5 [95%CI, 3.8-5.4] months, p = 0.03), and similarly, the mPFS of FGFR1-amplified patients (FGFR1-type) (3.5 months [95%CI, 1.5-4.9]) tended to be shorter than that of nonNF-type (p = 0.07), although the response rates were equivalent among the three types. NRF2-type also showed shorter overall survival (OS) than nonNF-type (median OS, 10.4 [95%CI, 6.9-22.3] vs. 16.6 [95%CI, 13.6-21.7] months, p = 0.10). Therapeutic efficacy of nivolumab or pembrolizumab was not different among these types in the current follow-up data. Conclusions: Our large scale genome screening identified specific gene alterations for SqLC and the alterations were associated with a less efficacy of chemotherapy and worse prognosis, suggesting the need for the development of genotype-directed therapeutic strategy for SqLC patients.
Crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase II clinical trial–Updated report on progression-free and overall survival.
Authors: Michels Sebastian Yves Friedrich , Franklin Jeremy , Massuti Bartomeu , Sebastian Martin , Schildhaus Hans-Ulrich , Felip Enriqueta , Grohe Christian , Rodriguez-Abreu Delvys , Bischoff Helge , Carcereny Enric , Corral Jesús , Dingemans Anne-Marie C. , Insa Amelia , Reck Martin , Rothschild Sacha , Smit Egbert F. , Provencio Mariano , Büttner Reinhard , Rosell Rafael , Wolf Juergen 
Published: March 2020

9066 Background: ROS1 rearrangements are found in 1% of non-small cell lung cancer (NSCLC) patients. Early clinical trials in the US and East Asia have proven the therapeutic efficacy of crizotinib in this subset of patients. EUCROSS is the first prospective European trial to evaluate the acitivity of crizotinib in ROS1-positive lung cancer. Here we present an updated analysis of the investigator-assessed progression-free survival (PFS) and overall survival (OS). Methods: EUCROSS is a multi-centre, single arm phase 2 trial (NCT02183870). Key eligibility criteria: ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation). Treatment with crizotinib was initiated at a dose of 250 mg twice daily. Primary endpoint of the trial: investigator-assessed objective response rate (ORR) in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1). Key endpoints of this report: updated PFS and OS and updated molecular characterization of tumour tissue. Results: Thirty-four patients received treatment with crizotinib and were included in the intention-to-treat analysis. Four patients were excluded from the primary endpoint analysis due to violation of eligibility criteria (response-evaluable set, N = 30). Median follow-up period was 44.9 months. At the time of data cut-off for this report 19 patients (63%) discontinued treatment due to progression or death. Investigator ORR was 70% (95% CI, 51–85; 21/30), disease control rate was 90% (95% CI, 73.5-97.9; 27/30) and median PFS was 19.4 months (95% CI, 10.1-31.2). Median OS was not reached, but 24-months-OS probability was 66% (95% CI, 48.3-82.9). Tissue of 18 patients was available for hybrid-capture-based sequencing. Co-occurring genetic aberrations were found in 61% (11/18). TP53 mutations were most frequent (28%; 5/18). PFS (24-months probability, TP53-mut. 0% vs. TP53 wild-type (wt) 61%; p = 0.0219) and OS (24-months, TP53-mut. 40% vs. TP53 wt 83%; p = 0.015) were significantly shorter in TP53-mutant patients. Differences in OS and PFS stratified by number of prior treatment lines (0-1 vs. > = 2), brain metastases (yes vs. no) or CD74-rearrangement ( CD74- ROS1 vs. other fusion type) status were not significant. Conclusions: Updated PFS and OS results show that crizotinib is highly effective in ROS1-rearranged lung cancer. Co-occurring TP53 mutations were associated with a significantly worse outcome. Clinical trial information: NCT02183870.
Whole exome sequencing (WES) of non-small cell lung cancer (NSCLC) for tumor mutational burden (TMB) analysis and long-term benefit to immune checkpoint inhibitors (ICIs).
Authors: Felip Enriqueta , Navarro Alejandro , Callejo Ana , Martinez Marti Alex , Cedres Susana , Pardo Nuria , Ros Javier , Assaf Juan David , Pedrola Anna , Viaplana Cristina , Sansano Irene , Jimenez Jose , Nuciforo Paolo , Sansó Miriam , Dienstmann Rodrigo , Amat Ramon , Mancuso Francesco M , Vivancos Ana 
Published: March 2020

9071 Background: ICIs have significantly changed the therapeutic landscape of advanced NSCLC. As such, characterizing predictive markers of long-term clinical benefit is a critical objective. TMB quantification using targeted gene panels associates with long-term response to ICIs in NSCLC patients (Rizvi H ASCO 18). Although TMB quantified by targeted NGS correlates with that of WES, caution may be needed when using smaller panels. Methods: Here we analyzed WES of tumors and matched normal tissue from 67 NSCLC patients including 42 treated with ICIs. We correlated TMB with clinico-pathological features and outcomes. TMB was categorized as high vs. low according to the upper quartile of cohort distribution. Results: The median TMB was 2.68 non-synonymous variants (nSNVs)/Mb, ranging from 0 to 15.6 nSNVs/Mb, with upper quartile at 5.42 nSNVs/Mb. TMB was higher for smoker/current smoker (median 3.51) compared to never smokers (median 0.94, p = 0.0048) but no differences were seen in elderly ( > 70 years) vs. young patients or across histologies (squamous, adeno and other) and stages at diagnosis. In patients treated with ICIs, median TMB was 5.44 for those achieving complete response, 3.87 for patients with partial response and 2.42 for patients with progressive disease (PD) (p = 0.04). Moreover, improved clinical outcomes were associated with higher TMB (Table). In patients treated with ICIs, TMB as continuous variable had an impact on progression free survival (PFS) (p = 0.03). Median PFS was 22.3 months (mo) (14-not reached) for those with high TMB and 6.4 mo (3-16) for those with low TMB (HR 0.34, 0.13-0.9, p = 0.03). Median overall survival was not reached for those patients with high TMB and 32 mo (22-43) for those with low TMB (HR 0.29, 0.1-0.86, p = 0.02). Conclusions: High TMB correlates with long-term ICI benefit in NSCLC patients. Mutations in individual genes potentially linked to long-term benefit or resistance to ICIs will be presented. [Table: see text]
First-in-human phase 1 study of the antibody-drug conjugate (ADC) SAR408701 in advanced solid tumors: Dose-expansion cohort of patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC).
Authors: Gazzah Anas , Cousin Sophie , Boni Valentina , Ricordel Charles , Kim Tae Min , Kim Jin-Soo , Helissey Carole , Gardeazabal Itziar , Chadjaa Mustapha , Allard Aurore , Yoruk Semra , Barlesi Fabrice 
Published: March 2020

9072 Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is a cell-surface glycoprotein highly expressed in several tumor types. This Phase 1, open-label, dose-escalation, dose-expansion study (NCT02187848) investigated SAR408701, a DM4 conjugated ADC targeting CEACAM5, in pts with advanced solid tumors. During dose escalation, maximum tolerated dose (MTD) of SAR408701 was 100 mg/m2 IV once every 2 weeks in 14-day cycles. Interim analysis of an ongoing expansion cohort in pts with NSQ NSCLC with CEACAM5 expression in ≥ 50% of the tumor cell population is reported. Methods: SAR408701 was administered at MTD. Primary endpoint: overall response rate (ORR; expansion phase). Secondary endpoints include safety and pharmacokinetics (PK). Tumor assessments were performed every 4 cycles (8 weeks). Results: As of Aug 2, 2018, 22 pts with NSQ NSCLC (21 adenocarcinoma; 1 not yet reported) received SAR408701 at MTD. Median age: 60 years; male: 72.7%; ECOG PS (n = 21): 0 = 38.1%, 1 = 61.9%. Median number of prior anticancer therapies for advanced disease was 3; 66.7% (14/21) received ≥ 3 lines; 59.1% had prior anti-tubulin-based treatments. Pts received a median of 6.5 cycles. 15 pts discontinued due to progressive disease and 1 due to an adverse event (AE; peripheral neuropathy); 6 pts remain on study. ORR was estimated at 22.7% (5/22 pts; 90% CI 11.5–39.9); 40.9% had stable disease. Most frequently occurring all-grade treatment-emergent AEs (TEAEs) were corneal events (40.9%; including keratitis 22.7% [1 Grade 3] and keratopathy 18.2%), dyspnea (31.8%; 5 Grade ≥ 3), asthenic conditions (31.8%) and diarrhea (27.3%). 6 pts had ≥ 1 dose modification due to a TEAE. PK analysis was performed in 14 pts at Cycle 1; mean Cmax, AUC, clearance and t1/2z were 53.1 µg/mL, 297 µg.day/mL, 0.685 L/day and 6.19 days, respectively. Conclusions: In pts with advanced NSQ NSCLC and CEACAM5 expression in ≥ 50% of tumor cells, SAR408701 had a favorable safety profile. Interim analysis of 22 pts achieved the predefined boundary for efficacy (≥ 4 of 30 pts). These data support further development in NSQ NSCLC. Funding: Sanofi Clinical trial information: NCT02187848.
Nintedanib plus docetaxel in lung adenocarcinoma patients (pts) following treatment with immune checkpoint inhibitors (ICIs): Preliminary efficacy and safety results of the non-interventional study VARGADO.
Authors: Grohé Christian , Blau Wolfgang , Gleiber Wolfgang , Haas Siegfried , Mueller-Huesmann Harald , Schulze Mathias , Atz Judith , Kaiser Rolf 
Published: March 2020

9074 Background: The treatment landscape of non-targetable advanced NSCLC pts has changed considerably following the introduction of ICIs. Data are scarce regarding optimal treatment choice and treatment sequence for pts who progressed on ICI. Methods: VARGADO (NCT02392455) is a prospective non-interventional study investigating the efficacy and tolerability of the oral triple angiokinase inhibitor nintedanibplus docetaxel in pts with advanced lung adenocarcinoma after first-line chemotherapy. The present analysis focused on its clinical activity in pts who received nintedanib plus docetaxel in 3rd line following progression on ICIs in 2nd line. Results: 25 pts whose disease has progressed on previous ICI therapy received subsequently nintedanib plus docetaxel. Median age was 59 years (range: 45 – 76); 17/25 pts (68.0%) were men, 17/25 pts (68.0%) were ECOG PS0/1, and 24/25 pts (96.0%) were current or former smokers. 1st line chemotherapy included pemetrexed (18/25 pts, 72.0%), cisplatin (15/25 pts, 60.0%), carboplatin (12/25 pts, 48.0%), bevacizumab (8/25 pts, 32.0%), vinorelbine (4/25 pts, 16.0%), paclitaxel (2/25 pts, 8.0%), and docetaxel (1/25 pts, 4.0%). 2nd line treatment included nivolumab (18/25 pts, 72.0%) and pembrolizumab (6/25 pts, 24.0%). Under nintedanib and docetaxel, 9/20 pts (45.0%) showed a partial response, and 7/20 pts (35.0%) showed stable disease, resulting in a DCR of 80.0% (16/20 pts). Median PFS was 5.5 months (95%CI 2.5 – 8.2). Treatment emergent adverse events (TEAEs) grade ≥3, serious TEAEs, and TEAEs leading to discontinuation occurred in 15/25 pts (60.0%), 13/25 pts (52.0%), and 9/25 pts (36.0%), respectively. Conclusions: Nintedanib, in combination with docetaxel, showed clinically meaningful efficacy and an acceptable safety profile in advanced lung adenocarcinoma pts following chemotherapy and ICIs. These findings support the use of nintedanib plus docetaxel as a therapeutic option in lung adenocarcinoma pts progressing under ICI therapy. Clinical trial information: NCT02392455.
Randomized multicenter phase II trial evaluating the sequencing of PD-1 inhibition with pembrolizumab (P) and standard platinum-based chemotherapy (C) in patients (pts) with metastatic non-small cell lung cancer (NSCLC) (AFT-09).
Authors: Hensing Thomas A. , Wang Xiaofei F. , Gao Junheng , Stinchcombe Tom , Knopp Michael V. , Dudek Arkadiusz Z. , Graziano Stephen L. , Patel Jyoti D. , Faller Bryan , Dragnev Konstantin H. , Kozono David E. , Vokes Everett E. 
Published: March 2020

9088 Background: KEYNOTE-024 established single-agent P as a 1st-line option for pts with metastatic NSCLC without targetable alterations and PD-L1 tumor proportion score (TPS) ≥ 50%. KEYNOTE-189 and 407 established concurrent C + P as a treatment option irrespective of PD-L1 expression. In this randomized phase II selection trial, we explored sequencing of C and P in this pt. population. Methods: Eligible pts were randomized 1:1 to (arm A) C (carboplatin (AUC 6) + pemetrexed 500 mg/m2 (non-squamous) or paclitaxel 200 mg/m2 (squamous)) x 4 cycles followed by P 200 mg x 4 cycles, or the reverse sequence (arm B) of P x 4 cycles followed by C x 4 cycles. After 8 cycles, pts on both arms were eligible to receive maintenance P for up to 24 months. Primary endpoint was objective response rate (ORR) per RECIST 1.1 by independent review. Secondary endpoints included progression free survival (PFS) per RECIST 1.1 and overall survival (OS). Efficacy endpoints were also evaluated by PD-L1 expression. Results: 89 pts (47 arm B & 42 arm A) were enrolled and are included in the analysis (PD-L1 TPS 0/1-49%/≥50% = 24 pts (34%)/25 pts (36%)/21 pts (30%)). There was no significant difference in ORR (36% vs 38%, p = 0.829), median PFS (2.7 vs 5.5 months (mo), HR 1.25, 95% CI 0.77-2.02, p = 0.363) or OS (13.1 vs 19.8 mo, HR 1.25, 95% CI 0.69-2.25, p = 0.4573), arm B (Px4→C) vs arm A (Cx4→P). Multivariable Cox regression analysis demonstrated significant interaction between treatment and PD-L1 TPS ( < 50% vs ≥ 50%) for PFS (HR 6.76, 95% CI 2.14-21.35, p = 0.0011) and a trend for OS (HR 5.02, 95% CI 0.92-27.55, p = 0.0632), arm B vs arm A. Incidence of grade ≥3 adverse events was 71% for arm A and 65% for arm B. No new safety signals were observed. Conclusions: In pts with stage IV NSCLC and PD-L1 TPS ≥ 50% there was an observed improvement in PFS and OS in favor of C followed by P vs P x 4 followed by C. Given small # of pts and trial design, this observation should be considered hypothesis-generating, but supports further exploration of sequential C + P in this setting. Support:Merck Sharp & Dohme Corp.; https://acknowledgments.alliancefound.org Clinical trial information: NCT02591615.