Median Relative Dose Intensity Research Articles

Relative dose intensity (RDI) of nab-P in gem+nab-P combination in pancreatic cancer treatment and the prognostic role of baseline NLR.

e16269 Background: Combination of Gem+Nab-P is considered as a dose intense regimen which exhibits synergistic cytotoxic activity and equally effective in increasing survival as FOLFIRINOX regimen in pancreatic cancer. However, number of patients who tolerates such dose intense regimen is found to be less in Indian population. The importance of maintaining optimum RDI is well-known however a low RDI may reflect a poor tolerability. Therefore, the present study aimed to identify desired relative dose intensity and explore the potential of baseline NLR as a prognostic biomarker. Methods: A retrospective chart review was performed of 26 patients with a median age of 65.5 years who received this drug combination either as first-line or second-line treatment for pancreatic adenocarcinoma at a single institution. Treatment outcome was measured using overall survival and toxicities were classified according to CTCAE guidelines. The thresholds for RDI of Gem and Nab-P, and baseline NLR cut-off for predicting survival was calculated by constructing ROC curves. Results: Median overall survival was 11.5 months. Median RDI of Gem and Nab-P was found to be 79% (30-94) and 71% (39 –114) respectively. We estimated a RDI cut-off of 67% in Nab-P and 68% in Gem and observed a statistically significant favorable outcome in patients who received Nab-P with RDI > 67% ( p-0.021). No significant relationship of Gem RDI with outcome was observed. Median overall survival was found to be higher in patients with a baseline NLR < 2.35, patients on D1, D8, D15 treatment regimen and those who received Nano particle bound paclitaxel. Complete assessment of study subjects are enlisted in the table. Grade 3 neuropathy, fatigue, and hyponatremia were reported in 2, 5 and 4 patients respectively. Grade 2 skin rashes and neuropathy were seen in 3 patients each. Conclusions: Our study concludes that tolerability of Gem+Nab P is a concern and it is expected to exhibit a durable response only if it achieves an optimum RDI of Nab-P. The study indicates varied efficacy in different pharmaceutical preparations of paclitaxel favoring the use of nano-particle formulations. The study also indicates that baseline NLR is an important prognostic biomarker in pancreatic cancer[Table: see text]

Real-World Therapeutic Outcomes of S-1 Adjuvant Chemotherapy for pStage II/III Gastric Cancer in the Elderly

Background: The predictive factors for discontinuation of S-1 administration and prognostic factors in elderly patients with pStage II/III gastric cancer receiving S-1 adjuvant chemotherapy remain unclear. Methods: Between January 2004 and December 2016, 80 elderly gastric cancer patients (≥70 years) undergoing curative D2 gastrectomy were enrolled in this study. Predictive factors for completion of S-1 administration over 1 year, adverse events due to S-1 administration, and prognostic factors for overall survival (OS) and relapse-free survival (RFS) were evaluated. Results: Twenty-eight patients (35%) completed 8 courses of S-1. The median relative dose intensity was 82.1% (IQR 31.1–100%). The incidence rates of hematological and nonhematological adverse events were acceptable. Distal gastrectomy was an independent predictive factor for completion of S-1 administration (odds ratio [OR] 0.364; 95% confidence interval [CI] 0.141–0.939; p = 0.037). Higher postoperative neutrophil count/lymphocyte count (N/L) ratio and more advanced stage adversely influenced OS. Multivariate analysis revealed that a higher postoperative N/L ratio and more advanced stage adversely affected RFS. Conclusion: To complete adjuvant S-1 administration to elderly patients with pStage II/III gastric cancer, total gastrectomy should be avoided if possible. A new regimen for elderly gastric cancer patients with higher postoperative N/L ratios and more advanced stage should be established.

Belinostat in combination with standard cyclophosphamide, doxorubicin, vincristine and prednisone as first-line treatment for patients with newly diagnosed peripheral T-cell lymphoma

BackgroundBelinostat is a histone deacetylase inhibitor approved for relapsed refractory peripheral T-cell lymphoma (PTCL). The primary objective of this study was to determine the maximum tolerated dose (MTD) of belinostat combined with CHOP (Bel-CHOP). Secondary objectives included safety/tolerability, overall response rate (ORR), and belinostat pharmacokinetics (PK).MethodsPatients were ≥ 18 years with histologically confirmed, previously untreated PTCL. Patients received belinostat (1000 mg/m2 once daily) + standard CHOP for 6 cycles with varying schedules using a 3 + 3 design in Part A. Part B enrolled patients at MTD dose.ResultsTwenty-three patients were treated. One patient experienced DLT (Grade 3 non-hematologic toxicity) on Day 1–3 schedule, resulting in escalation to Day 1–5 schedule (n = 3). No DLTs were observed and Day 1–5 schedule with 1000 mg/m2 was declared as MTD. Twelve additional patients were enrolled in Part B using MTD. Median relative dose intensity was 98%. All patients experienced adverse events (AEs), including nausea (78%), fatigue (61%), and vomiting (57%). Serious AEs occurred in 43%, with febrile neutropenia (17%) and pyrexia (13%). Overall ORR was 86% with 71% reported CR at MTD. Belinostat PK parameters were similar to single-agent.ConclusionsBel-CHOP was well tolerated and MTD in CHOP combination was the same dose and schedule as single agent dosing.Trial Registration: ClinicalTrials.gov Identifier: NCT01839097.

Abstract PS13-25: Management of abemaciclib associated diarrhea in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Analysis of the MONARCH plus study

Abstract Background: In the phase III MONARCH plus study (NCT02763566) the cyclin-dependent kinase (CDK) 4&6 inhibitor abemaciclib in combination with non-steroidal aromatase inhibitors (NSAI) or with fulvestrant compared with placebo demonstrated its efficacy and acceptable safety profile at interim analysis in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locoregionally recurrent or metastatic breast cancer. One of the most common treatment-emergent adverse event (TEAE) was diarrhea, typically low grade and of early onset. We will further characterize abemaciclib-associated diarrhea and describe its management in MONARCH plus trial. Methods: MONARCH plus study included two cohorts of patients. Cohort A enrolled patients with initial treatment of endocrine therapy, received abemaciclib or placebo plus NSAI (anastrozole or letrozole); Cohort B enrolled patients who progressed on prior endocrine therapy, receiving abemaciclib or placebo plus fulvestrant. The relative dose intensity was defined as the percentage of actual dose received relative to the planned dose. The severity of diarrhea was reported by investigators and graded according to Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0). Further analysis on diarrhea included time to onset, duration, supportive medication and dose modifications. Progression-free survival (PFS) was defined as time from randomization to death or progression (RECIST v1.1), and a stratified Cox proportional hazard model was used to estimate the hazard ratio (HR) between study intervention arm and placebo arm. Results: The median relative dose intensity of abemaciclib in abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm were 96.77% and 96.30% respectively. In abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm, the median time to onset of first reported diarrhea was 7 and 6 days and majority of diarrhea events occurred early (66.3% and 71.2% of patients reported diarrhea in Cycle 1 respectively). Diarrhea was typically of low grade (3.9% and 1.9% of patients reported Grade 3 in abemaciclib plus NSAI arm and abemaciclib plus fulvestrant arm, no Grade 4 diarrhea was reported in either arm). Median duration of grade ≥ 3 diarrhea was 2.5 and 3.5 days. Diarrhea was managed by dose adjustments and/or supportive medication (Table 1). Dose reductions were present in 2.0% and 2.9% of patients, and anti-diarrhea therapy was received in 30.2% and 32.7% of patients with abemaciclib plus NSAI and abemaciclib plus fulvestrant arm, respectively. As data cutoff, most diarrhea events were reported as resolved, and the incidence dropped below 10% (Grade 2) and 1% (Grade 3) by Cycle 2 in both arms and kept low incidence over time. Compared to the placebo arm, patients treated with abemaciclib combination who reported diarrhea within the first 7 days (abemaciclib + NSAI, HR [95% CI]: 0.289 [0.166, 0.502]; abemaciclib + fulvestrant, HR [95% CI]: 0.371 [0.213, 0.647]) had significant improvement in PFS. Conclusion: Majority of diarrhea events were of low grade in severity and well managed by anti-diarrheal medications, dose omissions or/and dose reductions in MONARCH plus patients. Table 1. Summary of dose adjustments and supportive medications in patients experiencing diarrheaCohort ACohort BAbemaciclib + NSAIAbemaciclib + FulvestrantN = 205N = 104Diarrhea (any grade), n (%)164 (80.0)82 (78.8)1105 (51.2)52 (50.0)251 (24.9)28 (26.9)38 (3.9)2 (1.9)Outcome, number of events, n796333Recovered/resolved, n (%)757 (95.1)318 (95.5)Not recovered/resolved, n (%)17 (2.1)7 (2.1)Treatment change, n (%)Dose reduction4 (2.0)3 (2.9)Dose omission3 (1.5)3 (2.9)Treatment discontinuation00Anti-diarrhea therapies, n (%)62 (30.2)34 (32.7)loperamide48 (23.4)21 (20.2)berberine6 (2.9)6 (5.8) Citation Format: Zefei Jiang, Xichun Hu, Qingyuan Zhang, Tao Sun, Yongmei Yin, Huiping Li, Min Yan, Zhongsheng Tong, Christina Pimentel Oppermann, Yunpeng Liu, Romulo Costa, Man Li, Xi Chen, Ying Cheng, Quchang Ouyang, Ning Liao, Xiaojia Wang, Xinhong Wu, Jifeng Feng, Roberto Hegg, Govindbabu Kanaka Setty, Amit Agarwal, Jyoti Bajpai, Jing Cheng, Gustavo Girotto, Chanchal Goswami, Wenjing Hu, Jian Huang, MA Coccia Portugal, Jin Yang, Rongsheng Zheng, Fabio Andre Franke, Qiang Liu, Yunjiang Liu, Yongkui Lu, Cristiano Souza, Shiying Yu, Nalini Kilara, Harsha Panchal, Ashish Singh, Shona Nag, Jian Liu, Bernardo Rapoport, Neonyana Keorapetse Rebecca Tabane, Hongxia Wang, Ning Wang, Rubing Han, Wanli Zhang. Management of abemaciclib associated diarrhea in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: Analysis of the MONARCH plus study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-25.

Impact of omitting fluorouracil from FOLFIRI plus bevacizumab as second-line chemotherapy for metastatic colorectal cancer patients.

76 Background: FOLFIRI + bevacizumab (FOLFIRI + BEV) is a standard second-line chemotherapy (Cx) for metastatic colorectal cancer (mCRC) patients (pts) who are refractory or intolerant to fluoropyrimidines (FPs) and oxaliplatin (OX). However, the efficacy of continuing FPs as second-line Cx for pts who are refractory to FPs in first-line Cx remains unclear. Methods: We retrospectively evaluated mCRC pts who received irinotecan (IRI) + BEV or FOLFIRI + BEV as second-line Cx at a single institution from Jan 2010 to Apr 2020. The main eligibility criteria were ECOG performance status (PS) of 0-2, known KRAS status, a standard initial dose of fluorouracil (5-FU) (bolus 400 mg/m2, infusional 2400 mg/m2) in FOLFIRI + BEV and IRI (150 mg/m2), refractory to FPs, no prior use of IRI, and prior use of OX. We compared the efficacy and safety of IRI + BEV with those of FOLFIRI + BEV. The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and overall survival (OS) were calculated using a multivariate Cox model that contained variables with p < 0.05 in the univariate analysis to reduce the imbalance between both the treatments. Results: Among the 261 pts, 107 were eligible (IRI + BEV/FOLFIRI + BEV, 31/76 pts). Pt characteristics were as follows (IRI + BEV/FOLFIRI + BEV): median age, 67/62; ECOG PS, 1–2, 55/46%; KRAS mutant, 45/50%; BRAF V600E mutant, 6/11%; right-sided tumor, 19/43%; lactate dehydrogenase (LDH) ≥ 400 U/L, 13/12%; PFS of first-line Cx < 6 month (m), 39/30%; prior use of BEV, 84/63%. Relative dose intensity (RDI) (IRI + BEV/FOLFIRI + BEV) of IRI and BEV was similar in the groups; median RDI (range) of IRI, 80 (44–100) /83 (49–100) %; p = 0.560; median RDI of BEV, 86 (35–100) /83 (20–100) %; p = 0.681. Efficacies (IRI + BEV/FOLFIRI + BEV) after a median follow-up of 13.1/14.3 m were as follows: median PFS, 6.4/5.8 m (HR, 0.90; 95% CI, 0.57–1.38; p = 0.64; aHR, 0.82; 95% CI, 0.50-1.34; p = 0.44); median OS, 16.6/16.5 m (HR, 0.83; 95% CI, 0.51-1.32; p = 0.44; aHR, 1.01; 95% CI, 0.59-1.69; p = 0.97); objective response rate, 25.9/11.3%. Adjustment factors for PFS were prior colorectomy, number of metastatic sites, ECOG PS, liver metastasis, and the level of LDH, while those for OS were prior colorectomy, number of metastatic sites, liver metastasis, peritoneal metastasis, and the level of LDH. All subgroup analyses for PFS and OS according to the pt characteristics also showed no significant differences in the groups. All grade nausea (32/58%) and stomatitis (13/36%) and grade 3–4 neutropenia (23/58%) and febrile neutropenia (0/3%) were less common in the IRI + BEV than in the FOLFIRI + BEV group. Conclusions: Our study suggests that omitting 5-FU from FOLFIRI + BEV as second-line Cx for mCRC pts who are refractory to FPs may lower the occurrence of adverse events without impairing the treatment efficacy.

Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

Higher average chemotherapy dose intensity improves prognosis in patients with aggressive adult T‐cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell lymphoma with poor prognosis. We retrospectively reviewed the medical records of 312 patients with aggressive ATL and analyzed the effect of chemotherapy dose intensity on prognosis in clinical practice. As first-line therapy, 62 patients underwent best supportive care (BSC) or single-agent chemotherapy, and 235 underwent intensive chemotherapy. The median survival time (MST) was 0.58years in the 312 total patients, and 0.13years and 0.75years in the BSC/single-agent chemotherapy group and intensive chemotherapy group, respectively. The median average relative dose intensity (ARDI) of patients who received intensive chemotherapy was 60%. We divided patients into 3 groups according to ARDI. Those in the top tertile of ARDI (ARDI≥75%, n=82) had better overall survival compared with those in the intermediate tertile (45%≤ARDI<75%, n=79) (P<.0001), with MSTs of 4.69 and 0.75years, respectively. The occurrence of organ dysfunction and infectious complications was comparable between the two ARDI groups. Higher ARDI improves prognosis in patients with aggressive ATL in clinical practice.

Efficacy and safety of chronomodulated irinotecan, oxaliplatin, 5-fluorouracil and leucovorin combination as first- or second-line treatment against metastatic colorectal cancer: Results from the International EORTC 05011 Trial.

The triplet combination of irinotecan, oxaliplatin and fluorouracil is an active frontline regimen in metastatic colorectal cancer, but scarce data exist on its use as salvage treatment. We aimed at assessing its safety and efficacy profiles with its circadian‐based administration (chronoIFLO5) as either first‐ or second‐line treatment, within the time‐finding EORTC 05011 trial. Five‐day chronoIFLO5 was administered every 3 weeks in patients with PS 0, 1 or 2. It consisted of chronomodulated irinotecan (180 mg/sqm), oxaliplatin (80 mg/sqm) and fluorouracil‐leucovorin (2800 and 1200 mg/sqm, respectively). For our study, toxicity and antitumour activity were evaluated separately in first‐ and second‐line settings. Primary endpoints included Grade 3‐4 toxicity rates, best objective response rate (ORR), progression‐free survival (PFS) and overall survival (OS). One‐hundred forty‐nine and 44 patients were treated in first‐line and second‐line settings, respectively, with a total of 1138 cycles with median relative dose intensities of about 90%. Demographics were comparable in the two groups. Thirty‐six (24.7%) and 10 (22.2%) patients experienced at least one episode of severe toxicity in first line and second line, respectively. Frontline chronoIFLO5 yielded an ORR of 62.3% [95% CI: 54.2‐70.4] and resulted in median PFS and OS of 8.7 months [7.5‐9.9] and 19.9 months [15.4‐24.5]. Corresponding figures in second line were 37.5% [22.5‐52.5], 6.7 months [4.8‐8.9] and 16.3 months [11.8‐20.8]. International and prospective evaluation revealed the favourable safety and efficacy profiles of chronoIFLO5, both as frontline and as salvage treatment against metastatic colorectal cancer. In particular, encouraging activity in second line was observed, with limited haematological toxicity.

Safety and efficacy of sorafenib followed by regorafenib or lenvatinib in patients with hepatocellular carcinoma.

Sequential administration of sorafenib followed by regorafenib or lenvatinib is effective against advanced hepatocellular carcinoma (HCC). In this study, we compared the safety profiles and anti-tumor effects of sequential sorafenib and regorafenib or lenvatinib therapy in patients with HCC. We investigated adverse events, treatment responses and dose intensities in patients with HCC who were consecutively treated with sorafenib followed by regorafenib or lenvatinib at the individual level. Each group included 20 patients. The safety profiles of regorafenib and sorafenib were similar. The severity of hypophosphatemia, palmar-plantar erythrodysesthesia syndrome, and decreased neutrophil counts associated with regorafenib or sorafenib was similar in 12 patients. Conversely, the incidences and grades of adverse events differed between sorafenib and lenvatinib treatment. The anti-tumor effects of regorafenib and lenvatinib compared with sorafenib were significantly different for each patient. The response to treatment and progression-free survival were comparable for regorafenib and lenvatinib. The median relative dose intensities during the first 56days of regorafenib and lenvatinib treatment were 83.6 and 80.0%, respectively. Similar adverse events were experienced by patients during consecutive treatment with sorafenib and regorafenib, which was not observed during treatment with sorafenib and lenvatinib. The obtained safety profile of sorafenib provided meaningful insights for selecting sequential therapy for patients with advanced HCC.

Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Previously Treated with ≥2 Tyrosine Kinase Inhibitors (TKIs

Efficacy and Safety Results from ASCEMBL, a Multicenter, Open-Label, Phase 3 Study of Asciminib, a First-in-Class STAMP Inhibitor, vs Bosutinib (BOS) in Patients (Pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Previously Treated with ≥2 Tyrosine Kinase Inhibitors (TKIs

Febrile neutropenia and role of prophylactic granulocyte colony-stimulating factor in docetaxel and cyclophosphamide chemotherapy for breast cancer

Febrile neutropenia (FN) incidence during docetaxel and cyclophosphamide (TC) chemotherapy, known as a high-risk regimen, differs among countries. The role of prophylactic granulocyte colony-stimulating factor (G-CSF) in FN is unclear. This study aimed to investigate FN frequency and relative dose intensity (RDI) of TC chemotherapy in patients with breast cancer and identify the correct population requiring prophylactic G-CSF. In total, 205 patients with breast cancer were scheduled for TC chemotherapy (docetaxel/cyclophosphamide 75/600 mg/m2, every 3 weeks, 4 cycles) as adjuvant chemotherapy. Trastuzumab (8 mg/kg; continued with 6 mg/kg) was administrated intravenously for human epidermal growth factor receptor 2 (HER2)-positive cancer. Fifty-five patients received primary prophylactic measures (G-CSF: 20 and antibiotics: 35). We investigated the frequency of FN and hospitalization, RDI, and the factors related to FN, adverse events, hospitalization, and RDI. FN occurred in 70 patients (35.7%). FN incidence was noted in 41.1% without any prophylactic measures and in 5.0% with prophylactic G-CSF. In multivariate analysis, the independent risk factors of FN were older age (≥ 60 years, P = 0.017) and without primary prophylactic G-CSF (P = 0.011). Eleven patients (5.6%) were hospitalized of which 8 (72.7%) were elderly. The median RDIs of docetaxel and cyclophosphamide were 96.7% and 99.7%, respectively. FN frequency during TC chemotherapy was high, and primary prophylactic G-CSF reduced FN incidence. Primary prophylactic G-CSF is an effective therapy for preventing FN during TC chemotherapy. However, prophylactic G-CSF should be considered for elderly patients based on the low hospitalization rate and the high RDI.

A phase II study of FOLFOXIRI plus bevacizumab as initial chemotherapy for patients with untreated metastatic colorectal cancer: TRICC1414 (BeTRI)

PurposeFOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes.MethodsTwelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR).ResultsOf the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8–77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively.ConclusionsFOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Outcomes in Patients with Classic Hodgkin Lymphoma Treated with ABVD: A Single-center Retrospective Study.

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.

Abstract CT081: Poziotinib activity and durability of responses in previously treated EGFR exon 20 NSCLC patients - a Phase 2 study

Abstract Introduction and Purpose of Study: Effective and approved therapy for treating non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations is an unmet medical need. Poziotinib is a potent tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 insertion mutants. We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations (ZENITH20-1) in an independent cohort of a multi-cohort, multi-center Phase 2 study. Methods: Poziotinib (16 mg) was administered orally QD, allowing dose reductions for AEs, with follow up for 24 months. The primary endpoint was objective response rate (ORR), evaluated by central radiographic review using RECIST v1.1. The ORR endpoint was to be met if the lower bound of 95% CI&amp;gt;17% in the As-Treated Population. The secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety. Safety monitoring was conducted throughout the study. Results: A total of 115 patients with a median age of 61 years (33-83) were enrolled. Patients had received and failed prior therapy (median of 2 [1-9]) with majority receiving both chemo and immunotherapy. The median relative dose intensity was 72% (7-100%) with 65% having dose reductions. 10% of patients discontinued due to related AEs. The ORR was 14.8% (95% CI 8.9%-22.6%), and the DCR was 68.7% (95% CI 59.4%-77.0%). Seventeen patients had a confirmed partial response (PR), 5 patients had unconfirmed PR and 62 (53.9%) patients had stable disease (SD). Overall, 75 (65%) patients had tumor size reductions. The median DoR was 7.4 months (95% CI 3.7-9.7) and the median PFS was 4.2 months (95% CI 3.7-6.6). Safety profile was mechanism related and similar to other 2nd generation tyrosine kinase inhibitors with the most common treatment-related Grade ≥3 AEs (preferred term) being rash (28%), diarrhea (26%), stomatitis (9%) and paronychia (6%). The incidence of treatment-related pneumonitis, an important AE associated with TKIs, was 4%. Conclusion: Although the ORR primary endpoint was not met, poziotinib induced tumor size reduction in the majority (65%) of patients. The tumor size reduction combined with long duration of response demonstrated the clinical activity of poziotinib in treating this patient population. We are further optimizing dosing and AE management. Citation Format: Xiuning Le, Jonathan Goldman, Jeffrey Clarke, Nishan Techekmedyian, Zofia Piotrowska, David Chu, Gajanan Bhat, Francois Lebel, Mark Socinski. Poziotinib activity and durability of responses in previously treated EGFR exon 20 NSCLC patients - a Phase 2 study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT081.

Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients.

9514 Background: Treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations is an unmet medical need. Poziotinib is a potent tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 insertion mutants. We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations in an independent cohort of a multi-cohort, multi-center Phase 2 study ( ZENITH20-1). Methods: ZENITH20-1 study enrolled pts with advanced NSCLC with an EGFR exon 20 insertion identified on local tissue testing who had received at least one prior line of therapy. Poziotinib (16 mg) was administered orally QD, allowing dose reductions for AEs, with follow up for 24 months. The primary endpoint was objective response rate (ORR), evaluated centrally by RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety. Efficacy was also evaluated by specific exon 20 insertions and prior lines of therapy. Results: 115 patients with a median age of 61 years (33-83) were enrolled. Patients had a median of 2 prior lines of therapy (range, 1-9.) The median relative dose intensity was 72% (7-100%) with 65% having dose reductions. The ORR in the as-treated population was 14.8% (95% CI 8.9 - 22.6%), and the DCR was 68.7% (95% CI 59.4 - 77.0%) with a median DoR of 7.4 months. 65% patients had tumor size reductions and the median PFS was 4.2 months. In the evaluable population (n = 88), the ORR was 19.3% and the unconfirmed ORR was 25%. Responses were predominantly observed in insertions between residues M766 to D770 of exon 20 (8/44; 18.2%). Responses were observed in patients with 2 lines (14%); ≥3 lines of therapy (16.2%). The most common treatment-related Grade ≥3 AEs were rash (28%), diarrhea (26%), stomatitis (9%) and paronychia (6%). The incidence of treatment-related pneumonitis was 4%, however some cases may have been confounded by prior checkpoint inhibitors as first line treatment. Conclusions: Although the ORR primary endpoint was not met, poziotinib induced tumor reduction in the majority of patients with durable responses, including the heavily pre-treated population. Responses were more common in patients with insertions between M766 to D770 of EGFR exon 20. The safety profile was overall consistent with other 2nd generation EGFR TKIs. Evaluation of these subgroups with refined dosing and improved toxicity management to maintain continuous treatment is warranted to assess the potential of poziotinib in Exon20 related tumors. Clinical trial information: NCT03318939 .

Efficacy and safety of the antibody-drug conjugate (ADC) SAR408701 in patients (pts) with non-squamous non-small cell lung cancer (NSQ NSCLC) expressing carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5).

9505 Background: We report updated safety and efficacy of DM4-conjugated anti-CEACAM5 ADC from the expansion part of the first-in-human study (NCT02187848; Gazzah A et al. J Clin Oncol. 2019;37:15, 9072) in 92 NSQ NSCLC pts. Methods: CEACAM5 expression was assessed by immunohistochemistry on archived tumor samples. Two cohorts of pts have been analyzed: moderate and high expressors, with CEACAM5 expression at ≥2+ intensity between ≥1% to &lt; 50% and ≥50% of the tumor cell population, respectively. SAR408701 was administered at 100 mg/m2 IV every 2 weeks. Tumor assessments were done every 4 cycles (8 weeks). Primary endpoint was overall response rate (ORR). Results: As of January 2020, 92 pts were treated: 28 moderate and 64 high expressors, with median age 62.5 years (31–91; 42.4% of pts ≥65), 51.1% male, 71.7% ECOG PS ≥1; median of 3 prior treatments (1–10 lines) for advanced disease, including anti-tubulin agents (60.9%) and anti-PD1/PD-L1 (75%). In the moderate expressor cohort, 2 confirmed partial responses (PR) were observed (ORR 7.1%). In the high expressor cohort, 13 pts had confirmed PRs (ORR 20.3% [95% confidence interval 12.27%–31.71%]); 27 (42.2%) had stable disease; ORR of 17.8% was observed in 45 pts who had prior anti-PD1/PD-L1. Pts had a median of 7 (1–49) cycles; median relative dose intensity was 0.98. Six pts discontinued due to treatment-emergent adverse events (TEAEs). Most frequent TEAEs (all grades) were asthenia (38.0%), keratopathy/keratitis (38.0%), peripheral neuropathy (26.1%), dyspnea (23.9%), and diarrhea (22.8%). 31 pts had dose modification due to a TEAE, including dose reduction for keratopathy/keratitis in 10 pts. Hematological toxicity included leukopenia (14.4%), neutropenia (4.4%), and thrombocytopenia (13.3%). Grade ≥3 TEAEs occurred in 47.8% of pts and were assessed as drug-related in 15.2%. Conclusions: SAR408701 shows promising antitumor activity in heavily pretreated advanced NSQ NSCLC pts with high CEACAM5 expression. SAR408701 was well tolerated, with minimal hematological toxicity compared to conventional chemotherapy; keratopathy was reversible and manageable with dose modification. These data support the activity of SAR408701 in NSQ NSCLC CEACAM5 high expressors. A phase 3 trial evaluating the activity of CEACAM5-DM4 ADC monotherapy in comparison with docetaxel in NSQ NSCLC CEACAM5 high expressors after failure of standard first line chemotherapy and anti-PD1/PD-L1 is underway. Clinical trial information: NCT02187848 .

Phase I/II study of avadomide (CC-122) in combination with R-CHOP for newly diagnosed DLBCL.

3501 Background: In certain subsets of patients (pts) with diffuse large B-cell lymphoma (DLBCL), the failure rate of standard R-CHOP treatment is high. Pts with high-risk disease (International Prognostic score [IPI] 3-5) have a particularly poor prognosis, with 3-y survival rates of ~62% with R-CHOP alone. The cereblon E3 ligase modulator avadomide (CC-122) showed activity in pts with relapsed or refractory DLBCL. We report results of avadomide plus R-CHOP in previously untreated pts with high-risk DLBCL. Methods: CC-122-DLBCL-002 (NCT03283202) is a phase 1/2 study of avadomide plus R-CHOP-21 in pts newly diagnosed with DLBCL not otherwise specified with IPI scores 3-5 who were aged ≥18 y. Pts received standard R-CHOP and escalating doses (1-3 mg) of oral avadomide for up to six 21-d cycles (Table). All pts received pegfilgrastim support. Primary objectives were to assess safety, tolerability, and complete response (CR) rate. Secondary objectives include evaluation of additional efficacy parameters (objective response rate [ORR], progression-free survival [PFS], and overall survival) and biomarkers. Results: As of July 30, 2019, 35 pts were enrolled in the phase 1 part of the study. Median age was 66 y (range, 20-75), 23 pts (66%) were aged &gt; 60 y, 18 (51%) had an IPI score of 3, and 17 (49%) had an IPI score of 4-5. Thirty-two pts (91%) completed 6 cycles of treatment. Median relative total dose intensity of avadomide was 99% and the average relative dose intensity of R-CHOP was 95%. Six pts had dose-limiting toxicities: 1 pt had neutropenia and bacterial hepatic infection; 1 had pneumonia; 1 had febrile neutropenia (FN); 1 had FN and hypotension; 1 had FN due to skin infections; and 1 had sepsis. The recommended phase 2 dose was 3 mg 2/3 wk. Grade 3/4 adverse events in ≥10% of pts were neutropenia (54%), anemia (20%), leukopenia (20%), lymphopenia (14%), hypophosphatemia (14%), and FN (11%). Among 34 efficacy-evaluable pts, the ORR was 88% (n = 30/34), including a CR rate of 79% (n = 27/34) at the end of treatment. With a median follow-up of 10 mo, the 1-y PFS rate was 80% (95% CI, 58-92). Correlative analyses will be presented at the meeting. Conclusions: Avadomide plus R-CHOP was well-tolerated with no significant additive toxicities. The promising efficacy in this high-risk pt population warrants further evaluation of immunomodulatory drugs combined with immunochemotherapy for pts with previously untreated DLBCL. Clinical trial information: NCT03283202 . [Table: see text]

Modified FOLFIRINOX as a second-line therapy following gemcitabine plus nab-paclitaxel therapy in metastatic pancreatic cancer

BackgroundThere is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival.MethodsFrom 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2400 mg/m2 for 46 h without bolus infusion).ResultsIn total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2–9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8–5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5–100%), 77.2% (range 38.1–100%), and 85.9% (range 36.9–100%), respectively. Grade 3–4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6–16.3) and 7.6 months (95% CI 4.1–10.5) for the good prognostic factors, 6.5 (95% CI 5.5–10.0) and 3.6 months (95% CI 2.7–4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9–6.6) and 1.7 months (95% CI 0.9–4.3) for the poor prognostic factors, respectively.ConclusionsThe mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

Abstract P1-19-31: RIBECCA - A phase IIIb, multi-center, open label study for women with estrogen receptor positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole: Results of the third interim analysis

Abstract Introduction: RIBECCA is a national, multi-center, open-label, single-arm phase IIIb trial assessing the efficacy and safety of ribociclib in combination with letrozole in a patient population similar to the populations of MONALEESA-2, -3 and -7. Here we present the results of the third preplanned interim analysis. Methods: Main inclusion criteria allowed enrollment of men or women with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, and histological or cytological confirmation of HR+, HER2- breast cancer, irrespective of their menopausal status. The primary objective is to assess the clinical benefit rate (CBR) after 6 months. Secondary objectives include: progression free survival (PFS), overall survival (OS), safety and changes in quality of life. Here we describe a preliminary analysis baseline characteristics, safety data and the clinical benefit rate (CBR) at 24 weeks, of all enrolled patients (n=502). Results: The cut-off date for this third interim analysis was 6 months after the last patient was enrolled in the study. The median observation time for all patients in this analysis was 9.4 months (0.1-26.0 months). Baseline characteristics: of 502 pts, 497 were female and 5 male. Median age: 64 yrs; 46 pts pre-or perimenopausal, 451 postmenopausal (missing: 5); ECOG 0-1: 96.8%; median time since first recurrence: 1.6 months; 71.1 % of pts had bone metastases (40.8% bone only), 30.1% liver, 28.1% lung and 30.1% other metastases. Median relative dose intensity was 0.90 for ribociclib and 1 for letrozole. The most common treatment emergent AEs (all grades) were neutropenia and/or neutrophil count decreased (57.8%), nausea (41.2%), fatigue (37.5%), alopecia (34.5%), leukopenia or WBC decreased (29.7%), nasopharyngitis (24.7%), diarrhea (23.5%), ALT increased (21.5%) and AST increased (19.7%). The CBR by week 24 was 69.2%. Conclusion: The results of the third interim analysis confirmed clinical benefit in this patient population. No new safety signals were detected. This is in line with data published from the pivotal phase III studies MONALEESA-2, MONALEESA-3 and MONALEESA-7. Citation Format: Andreas Hartkopf, Arnd Nusch, Thomas Decker, Mattea Reinisch, Bernhard J Heinrich, Christian Kurbacher, Roswitha Fuchs, Hans Tesch, Petra Krabisch, Sara Brucker, Tanja N Fehm, Wolfgang Janni, Sherko Kümmel, Diana Lüftner, Andreas Schneeweiss, Martin H Schuler, Claudia Voges, Jörg Schubert, Peter A Fasching. RIBECCA - A phase IIIb, multi-center, open label study for women with estrogen receptor positive locally advanced or metastatic breast cancer treated with ribociclib (LEE011) in combination with letrozole: Results of the third interim analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-31.

Abstract P1-19-29: An integrated safety analysis of talazoparib monotherapy from five clinical trials (phase 1-3) in advanced cancers

Abstract Background: Talazoparib is a potent oral inhibitor of poly(ADP-ribose) polymerase (PARP) 1 and 2, which significantly improved progression-free survival versus standard-of-care chemotherapy in patients with HER2-negative advanced breast cancer (ABC; locally advanced/metastatic breast cancer) and a germline BRCA1/2 mutation (gBRCA1/2mut) in the Phase 3 EMBRACA trial (Litton J, et al. N Engl J Med. 2018;379:753-763). An integrated analysis of five clinical trials (Phase 1-3) in multiple tumor types was performed to evaluate the safety of talazoparib administered at 1 mg/day (d). Methods: Data were pooled from the ongoing Phase 3 randomized EMBRACA trial in HER2-negative gBRCA1/2mut ABC (NCT01945775), the Phase 2 non-randomized ABRAZO trial in gBRCA1/2mut ABC (NCT02034916), the Phase 1 trial in advanced/recurrent solid tumors (NCT01286987), the Phase 1 cardiac repolarization trial in advanced solid tumors (NCT03042910), and an ongoing open-label extension trial (NCT02921919). Results: 494 patients who received talazoparib 1 mg/d were included (Table). The most common all-grade adverse drug reactions (≥20%) with talazoparib were ANEMIA (includes preferred terms: anemia, decreased hemoglobin, decreased hematocrit; 49.6%), fatigue (47.6%), nausea (44.3%), NEUTROPENIA (neutropenia, decreased neutrophil count; 30.2%), THROMBOCYTOPENIA (thrombocytopenia, decreased platelet count; 29.6%), headache (26.5%), diarrhea (22.7%), alopecia (22.3%; Grade 1, 20.6%; Grade 2, 1.6%), vomiting (22.3%), and decreased appetite (20.2%). Grade 3/4 toxicities (≥10%) with talazoparib were ANEMIA (35.2%), NEUTROPENIA (17.4%), and THROMBOCYTOPENIA (16.8%). Overall 24 patients (4.9%) died within 30 days after the last dose of study drug; the most common cause of death was disease progression (13 patients; 2.6%). Other causes of death were reported in 1 patient each (cerebral hemorrhage, dyspnea, lung infection, lung metastases, respiratory failure, suspected veno-occlusive liver disease, and worsening of neurological symptoms); cause of death was not reported for 4 patients. The most common treatment-related serious adverse event was anemia (4.3%). Median duration of talazoparib exposure was 5.4 months (range, 0.0-61.1). Median relative dose intensity (defined as actual-dose intensity/planned-dose intensity) was 92.8%. Dosing interruptions due to TEAEs were reported for 48.6% of patients receiving talazoparib; median duration of dosing interruption due to TEAEs was 8.0 days (range, 1.0-121.0). Hematologic TEAEs (≥5%) associated with dose modification (interruption or reduction) included anemia (33.0%), neutropenia (15.8%), thrombocytopenia (13.4%), and decreased platelet count (5.9%); non-hematologic TEAEs (≥2%) associated with dose modification included fatigue (4.3%), vomiting (2.6%), and nausea (2.0%). Only 18 patients (3.6%) permanently discontinued due to a TEAE (anemia, 3 patients [0.6%]; other events, 1 patient each [0.2%]). Conclusions: Talazoparib monotherapy at 1 mg/d was generally well tolerated with few patients permanently discontinuing talazoparib due to AEs. Common toxicities were primarily hematologic and were manageable through dosing modifications and/or standard supportive care. Funding: Pfizer Inc. Table Summary of TEAEsPhase 3 EMBRACA trialOpen-label trialsTalazoparibTalazoparib mg/dTalazoparib 1 mg/d1 mg/d populationbTalazoparibPCTABRAZONCT01286987NCT03042910OLEaTotalN=286N=126N=83N=77N=37N=46N=494Any TEAE282 (98.6)123 (97.6)81 (97.6)75 (97.4)28 (75.7)39 (84.8)484 (98.0)Grade 3 or 4 TEAE193 (67.5)80 (63.5)54 (65.1)52 (67.5)9 (24.3)21 (45.7)326 (66.0)Treatment-related Grade 3 or 4 TEAE159 (55.6)61 (48.4)48 (57.8)36 (46.8)3 (8.1)14 (30.4)260 (52.6)SAE91 (31.8)37 (29.4)23 (27.7)27 (35.1)3 (8.1)14 (30.4)156 (31.6)Treatment-related SAE26 (9.1)11 (8.7)11 (13.3)3 (3.9)1 (2.7)1 (2.2)42 (8.5)TEAE primary reason for permanent discontinuation13 (4.5)7 (5.6)3 (3.6)002 (4.3)18 (3.6)TEAE associated with dose modification190 (66.4)75 (59.5)55 (66.3)46 (59.7)4 (10.8)15 (32.6)308 (62.3)All data are number (%) of patients; d, day; OLE, open-label extension; PCT, physician’s choice of chemotherapy; SAE, serious adverse event; TEAE, treatment-emergent adverse event;aInitiated treatment with talazoparib; monotherapy (1 mg/d) in either the originating or the extension trial;b35 patients who initiated talazoparib 1 mg/d in two of the trials and continued in the OLE are counted only once in the total number of patients Citation Format: Joannes Ettl, Jennifer Litton, Hope S. Rugo, Lida Mina, Miguel Martin, Nicholas Turner, Henri Roché, Zev Wainberg, Johann de Bono, Tiziana Usari, Mohamed Elmeliegy, Silvana Lanzalone, Akos Czibere, Liza DeAnnuntis, Sara A. Hurvitz. An integrated safety analysis of talazoparib monotherapy from five clinical trials (phase 1-3) in advanced cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-29.