2L Pts Research Articles

Abstract P4-01-42: Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer in the MONALEESA-2, -3, and -7 studies

Abstract Background: The MONALEESA (ML) studies showed significant PFS & OS benefits for 1L ribociclib (RIB) + endocrine therapy (ET) in patients (pts) with pre/peri & postmenopausal advanced breast cancer. The benefit of RIB beyond study treatment (tx) was also observed, with improvements in PFS2 & delays in time to 1st subsequent chemotherapy (CT). While there is currently no preferred tx for the next line post-progression on a CDK4/6 inhibitor (CDK4/6i), except alpelisib in pts with a PIK3CA mutation, guidelines encourage multiple lines of ET or ET-based therapies before switching to CT (except for visceral crisis). This pooled exploratory analysis of the ML studies examined outcomes of various tx strategies post progression on RIB + ET. Methods: Data from pts receiving 1L therapy in ML-2, -3, & -7 (NSAI cohort only & excluding pts with early relapse [≤ 12 mo after end of (neo)adjuvant ET] whose prognosis is closer to that of 2L pts) were pooled & pts receiving 1st subsequent therapies after progression were analyzed. Three groups of subsequent therapies were assessed: ET only, CT, & targeted therapy. Subsequent CT comprises CT +/- any other therapy; targeted therapy includes CDK4/6i, mTORi, PI3Ki, AKTi, etc, +/- ET. Subsequent CT & targeted therapy groups are mutually exclusive. Median duration of study tx, 1st subsequent therapy, & OS (from randomization to death) were analyzed by KM methods. Weighted Cox regressions were performed using inversed propensity scoring matching method (inverse probability tx weighting [IPTW]) to ensure compatible pt characteristics between tx arms. These are not randomized comparisons; only baseline characteristics were used for the estimation of propensity scores in the IPTW, imbalance of prognostic factors at progression may exist. Results: Median follow-up time was 74 mo. 461 pts treated with RIB (81%) & 440 (86%) with PBO discontinued study tx & received a subsequent therapy. In the RIB arms, the most common 1st subsequent therapies were ET only (40%), CT (29%), combination with targeted therapy (28%), & other (4%); for the PBO arms, 34% received CT as a 1st subsequent therapy & 31% each received ET only or combination with targeted therapy (5% received other). In 14% & 20% of pts in the RIB & PBO arms, the 1st subsequent therapy was a CDK4/6i, of these 31% & 12% were RIB. In general, regardless of type of 1st subsequent therapy, the duration of both the study tx & the 1st subsequent therapy was longer for pts treated with RIB vs PBO (Table). In both RIB & PBO arms, pts who received subsequent CT had the shortest duration on study tx, whereas those who received subsequent targeted therapy combination had the longest. Among pts on 1L RIB + ET, after matching pre-randomization baseline characteristics, subsequent CDK4/6i use was associated with the longest mOS (84 [84-NE] mo), followed by ET only (60 [51-68] mo), then a non-CDK4/6i targeted therapy (52 [43-72] mo); post-progression CT was associated with the shortest mOS (37 [32-48] mo). Conclusions: This large, pooled analysis of the ML studies shows that, in general, duration of any subsequent therapy was numerically longer post-1L RIB + ET vs PBO + ET, & subsequent CT was used less frequently for pts on RIB vs PBO. Both findings confirm that upfront tx with RIB does not worsen pt outcomes. This trend in enhancement of outcomes of subsequent therapies seen with 1L RIB suggests a post-tx effect that merits further exploration. Citation Format: Erika Hamilton, Laura M. Spring, Peter A. Fasching, Sandra Franco, Richard H DeBoer, Javier Cortés, Kevin Kalinsky, Dejan Juric, Aditya Bardia, Sina Haftchenary, Agnes Lteif, Juan Pablo Zarate, Liyi Cen, Patrick Neven. Pooled analysis of post-progression treatments after first-line ribociclib + endocrine therapy in patients with HR+/HER2− advanced breast cancer in the MONALEESA-2, -3, and -7 studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-42.

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma.

TPS623 Background: Despite advances in treatment for unresectable hepatocellular carcinoma (HCC), long-term survival rates remain poor. The combination of bevacizumab (Bev) and atezolizumab (Atezo) is the preferred frontline therapy for advanced HCC, but a minority of patients (pts) respond, and secondary resistance usually occurs within months. HCC has an immune-suppressed tumor microenvironment, mediated by activated immune checkpoint signaling and angiogenesis pathways, which may contribute to therapeutic resistance. RP3 is a genetically modified herpes simplex virus 1 (HSV-1) that expresses the fusogenic GALV-GP R- protein, an anti–CTLA-4 antibody-like molecule, CD40 ligand, and 4-1BB ligand. The direct oncolytic effect coupled with immune stimulation by RP3 in the tumor microenvironment is intended to provide systemic anti-tumor activity and reverse therapeutic resistance to anti-PD-1/PD-L1 agents. Pre-clinical data has demonstrated improved distribution of oncolytic HSV within tumors in combination with Bev supporting the clinical combination of RP3 with Bev. RP3 combined with anti-PD1 therapy has demonstrated clinical activity and safety in pts with various malignant solid tumors. This study will evaluate the safety and efficacy of RP3 combined with Atezo and Bev as 1st (1L) and 2nd (2L) line systemic therapies for inoperable and advanced HCC. Methods: The 1L and 2L cohorts will each enroll up to 30 pts with advanced, unresectable HCC. Pts in the 1L cohort may not have received prior systemic treatment; pts in the 2L cohort must have progressed on or following one prior line of systemic therapy, which must have included a PD-(L)1 directed agent. Key inclusion criteria include advanced unresectable HCC with at least 1 measurable tumor of ≥1 cm in longest diameter, Childs-Pugh Class A, and ECOG Score of 0 or 1. Important exclusion criteria include untreated esophageal and/or gastric varices with bleeding or at high risk for bleeding, and macroscopic invasion of tumor into major blood vessels and/or main bile ducts. Pts with a history of medically refractory hepatic encephalopathy and/or hepato-renal syndrome are also excluded. Pts in 1L cohort will receive 1200 mg Atezo and 15mg/kg Bev Q3W together with RP3 intratumorally (IT) Q3W for a total of up to 8 doses. In 2L pts will receive RP3 Q2W for 4 doses with Bev Q3W starting on C1D1, then RP3 and Bev Q3W for up to 4 more doses with Atezo Q3W being added on C4D1. The primary endpoint includes overall response rate (ORR) by RECIST v1.1. Secondary endpoints are safety, ORR using HCC mRECIST, duration of response, complete response rate, and progression-free survival.

Real World Comparison of Bruton Tyrosine Kinase Inhibitors and Venetoclax in Patients Diagnosed with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Introduction Bruton tyrosine kinase inhibitors (BTKi's) including ibrutinib and acalabrutinib and the B-cell leukemia/lymphoma-2 inhibitor (BCL-2i) venetoclax have demonstrated favorable efficacy in the front-line and relapsed/refractory settings and are now approved standards of care for patients (pts) with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). While these novel agents have been favorably compared to chlorambucil-based therapy and other chemoimmunotherapy (CIT) combinations, direct comparisons between BTKi and BCL-2i have not been conducted in any line of therapy. As ongoing clinical studies are years away from providing data on these comparisons, we conducted a real-world analysis to evaluate clinical outcomes of comparable pts with CLL/SLL who received either BTKi monotherapy (mono) or BCL-2i + CD20 in first or second lines (1L, 2L) in the United States. Methods We conducted a retrospective cohort study using de-identified pt records retrieved from the Flatiron Health Enhanced Database (EDM) from 8/1/2014 to 2/28/2022. Adult pts were included if they had a confirmed CLL/SLL diagnosis (ICD-10: C91.1x, C83.0X), received BTKi mono or BCL-2i + CD20 monoclonal antibody (mAb), and had two or more clinical encounters in the study period. Index date was defined as the first date of initiation of either BTKi or BCL-2i treatment (tx). Pts were followed to the earliest of end of clinical activity, death, or end of data availability (2/28/2022). Time-to-next-treatment (TTNT) was used to compare the clinical performance of BTKi vs. BCL-2i and was defined as the current treatment's index date to the initiation of the next line of therapy (LOT) or death. BTKi was compared to BCL-2i + obinutuzumab (O) in the 1L and to BCL-2i + any CD20 mAb in the 2L. Propensity Score Matching (PSM) was used to improve the comparability between the tx cohorts using age, gender, race, Rai stage, time from diagnosis to tx, del (17p) / del (11q), IGHV mutational status, ECOG status, total number of lines received in study period, and prior novel agent exposure. Every BCL-2i pt was matched with two BTKi pts. Unmatched pts in the BTKi cohort were excluded. Separate descriptive and Kaplan-Meier (KM) analyses were performed for 1L and 2L pts. Results A total of 5,226 pts met the inclusion criteria and were treated in the 1L (n=3,676) and 2L (n=1772) settings. In the 1L, 92.4% (n=3,397) received BTKi mono and 6.7% (n=246) received BCL-2i + O. In the 2L, 84.4% (n=1,496) received BTKi mono and 15.6% (n=276) received BCL-2i + CD20 mAb. After applying PSM, the two cohorts were well balanced on all selected matched baseline characteristics in 1L (n=738) and 2L (n=838). (Table 1) In the 1L, the mean age across cohorts was 66.0 years, and 26.8% were female. In the 2L, the mean age across the cohorts was 69.4 years, 32.9% was female, and 32.6% of the pts had prior novel agents (Table 1). The median TTNT was not reached (NR) for the BTKi or BCL-2i cohorts in 1L or 2L. In the 1L, the mean (95% CI) proportion of pts remaining on tx or in tx free observation at 24 mos was 95.6% (92.8%, 97.3%) for the BTKi cohort and 92.7% (94.8%, 96.6%) for the BCL-2i + O cohort. For the 2L, the mean (95% CI) proportion of pts remaining on tx or in tx free observation at 24 mos was 84.9% (81.0%, 88.1%) for the BTKi cohort and 80.4% (73.6%, 85.6%) for the BCL-2i +CD20 cohort (Figure 1). Overall, the BTKi cohort had significantly longer TTNT than that of BCL-2i cohort in 2L. The difference in TTNT was not statistically significant in 1L. Conclusion Findings from this study showed that BTKi mono delays pts’ TTNT compared to BCL-2i + CD20 mAb in the 2L setting with a trend toward longer TTNT in the 1L setting that did not reach statistical significance. For the first time and in the largest dataset described to date, this study provides evidence that when considering the choice of BTKi vs. venetoclax-based therapy in 2L, clinical outcomes may favor selection of BTKi therapy. This result has immediate implications for tx selection in current clinical practice, may serve to inform the results of ongoing randomized studies and provides insight for future clinical trial design. Future studies will include longer pt follow-up, additional pts added to the dataset, assessment of discontinuation reasons for each class of therapy and assessment of TTNT stratified by key molecular / genetic prognostic factors. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 660: Real-world prevalence of metastasis and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) with KRAS G12C and with or without STK11 or KEAP1 mutations

Abstract Introduction: KRAS mt are common in lung cancer, with G12C mt being the most prevalent in pts with aNSCLC. This study assessed pts with KRAS G12C aNSCLC with or without STK11 or KEAP1 mt. Methods: Pts diagnosed with aNSCLC between Jan 2011 and Dec 2019 in the US-based de-identified Flatiron Health-Foundation Medicine clinico-genomic database were included. Cox proportional hazards models adjusted for baseline demographics and clinical characteristics were used to analyze the effect of mutational status on OS in pts receiving immunotherapy (CIT), chemotherapy (chemo) or both (CIT+chemo). Results: Of 2217 1L pts, 454 (20.5%), 344 (15.5%) and 163 (7.4%) had tumors with KRAS G12C, STK11 and KEAP1 mt, respectively. Of 1019 2L pts, 234 (23.0%), 191 (18.7%) and 88 (8.6%) had tumors with KRAS G12C, STK11 and KEAP1 mt, respectively. A higher proportion of pts with KRAS G12C were females, PD-L1+ and had nonsquamous histology vs KRAS wildtype (WT) pts. Pts with KRAS G12C tumors had a higher cumulative incidence of mets (31.5% vs 25.8%) and brain mets (26.1% vs 18.8%) vs WT pts (P<0.001). No statistically significant difference was seen in the association of KRAS status with OS when stratifying by treatment type. In KRAS WT pts, STK11 mt vs WT pts had shorter OS in 1L (6.1 vs 9.4 mo) and 2L (4.5 vs 7.6 mo; Table); a similar trend was seen for pts receiving 1L CIT+chemo. In KRAS G12C pts, KEAP1 mt vs WT pts had shorter OS in 1L (4.9 vs 13.4 mo) and 2L (1.8 vs 9.4 mo); similar differences were seen in pts receiving 1L CIT+chemo or chemo. Conclusions: In pts with aNSCLC and KRAS WT, STK11 mt was associated with significantly worse OS; KRAS G12C co-occurring with KEAP1 mt had a similar result. Pts with STK11/KEAP1 mt have poor prognosis and high unmet medical need. This analysis highlights the importance of evaluating genomic alterations in clinical practice to better understand the interplay between treatment and survival. Table. Effect of KRAS mutational status and co-occurring known and likely STK11 and/or KEAP1 mutations on OS in patients with aNSCLC receiving any type of 1L or 2L therapy1L*2L†nMedian, mo (95% CI)HR‡ (95% CI)nMedian, mo (95% CI)HR‡ (95% CI)KRAS G12CSTK11WT32412.0(9.6-16.0)1.30(0.97-1.75)1699.2(7.8-11.4)1.05(0.68-1.63)STK11mt1047.5 (5.1-10.9)545.5(2.5-15.7)KEAP1WT35413.4(10.6-16.2)2.98§(1.91-4.64)1829.4(8.1-13.1)4.02§(2.10-7.70)KEAP1mt304.9(3.1-7.8)141.8(1.5-10.2)KRAS WTSTK11WT14599.4(8.5-10.6)1.57§(1.31-1.87)8477.6(6.5-8.8)1.66§(1.31-2.11)STK11mt2406.1(5.2-7.8)1374.5(3.5-7.6)KEAP1WT14059.3(8.3-10.5)1.43§(1.15-1.78)8137.6(6.4-8.8)1.25(0.93-1.68)KEAP1mt1336.2(4.7-7.8)744.9(3.3-8.0)1L, first line; 2L, second line; aNSCLC, advanced non-small cell lung cancer; HR, hazard ratio; Mb, megabase; mt; mutation; OS, overall survival; PD-L1, programmed death-ligand 1; TMB, tumor mutational burden; WT, wildtype.*Adjusted by age, sex, race, cancer type (de novo or recurrent), histology PD-L1 status, any metastases, TMB (mutations per Mb: <10 and ≥10), histology and treatment type.†Adjusted by age, sex, race, cancer type (de novo or recurrent), histology, PD-L1 status, any metastases, TMB (mutations per Mb: <16 and ≥16), histology and treatment type in 1L and 2L.‡HR comparing WT vs STK11 mt+ or KEAP mt+.§P<0.001. Citation Format: Cristina Julian, Navdeep Pal, Anda Gershon, Maria Evangelista, Hans Purkey, Peter Lambert, Zhen Shi, Qing Zhang. Real-world prevalence of metastasis and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) with KRAS G12C and with or without STK11 or KEAP1 mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 660.

METex14 ctDNA dynamics & resistance mechanisms detected in liquid biopsy (LBx) from patients (pts) with METex14 skipping NSCLC treated with tepotinib.

9012 Background: In the VISION study, tepotinib in METex14 skipping NSCLC pts (Cohort A) had robust and durable clinical activity. Serial LBx samples were collected for biomarker analyses, presented herein. Methods: LBx samples taken at baseline (BL), Week 6, 12, & end of treatment (EOT) were analyzed using Guardant360® CDx (73 genes). Investigator (INV)-assessed clinical outcome was evaluated per BL biomarker profiles and by molecular response (MR; defined as > 75% depletion from BL in METex14 variant allele frequency [VAF] ctDNA confirmed in 2 consecutive samples) or molecular progression (MP; defined as VAF increase > 0 from BL). Acquired resistance was investigated in EOT samples, following progression per INV. Results: LBx pts (n = 99) had a median age of 72 yrs (range 49–88), 53% were male, 44% never smokers, 85% had adenocarcinoma. INV ORR was 53% (95% CI 42, 63); ORR in 1L (n = 44) was 59% (43, 74) & ≥2L (n = 55) was 47% (33, 61). 94 pts had BL biomarker profiles; these were similar in 1L and ≥2L pts, except EGFR amp: 1/43 1L [2%] vs 8/51 ≥2L [16%]. Outcomes were not impacted by location/type of METex14 alteration. 1 pt with concomitant MET M1250T mutation had a PFS of 17.3 months. A trend towards better efficacy was seen in pts with concomitant MET amp (6 responses in 8 pts). Response to tepotinib occurred both in pts with wt or mutant TP53; however, there was a trend for longer mDOR in pts with wt TP53 (18.3 [95% CI 9.7, ne] vs 7.1 [4.7, 10.9] months) and mPFS (9.5 [6.7, 19.7] vs 5.1 [2.8, 6.9] months). Concomitant oncogenic mutations were rare, with no responses in 3 pts with KRAS, NRAS alterations and 3 responses in 5 pts with PI3K/AKT alterations. 65 pts had 2 consecutive on-treatment samples: 46 (71%) had confirmed MR, 5 (8%) had confirmed MP, 14 (22%) had no change in VAF or lacked confirmation. MR was associated with clinical response and MP was associated with no response/short PFS (Table). 52 pts with progression had EOT LBx samples. Emerging MET resistance mutations (Y1230H/C & D1228H/N) occurred in 7 (13%) pts, all responders and 5/7 had PFS > 10 months. Analyses on non-MET-driven resistance mechanisms will be presented. Conclusions: LBx biomarker analysis from the largest on-treatment data set for a MET inhibitor in METex14 skipping NSCLC, showed that ctDNA depletion in METex14 VAF is associated with improved clinical response in pts treated with tepotinib. This suggests serial LBx could help us to monitor response/non-response, understand resistance, and guide trials that test escalation/de-escalation strategies to improve outcomes and maximize QOL. Clinical trial information: NCT02864992. [Table: see text]

Abstract PS7-19: Pre/perimenopausal (preMeno) women receiving palbociclib (PAL) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) in a real-world setting: Treatment patterns from POLARIS

Abstract Background: POLARIS is an ongoing, prospective, real world, noninterventional study in patients (pts) with HR+/HER2– ABC receiving PAL. This interim report describes real-world PAL use in preMeno pts. Methods: POLARIS has a targeted enrollment of 1500 pts from ~110 sites in the United States and Canada. Using patient data collected from medical charts and physician surveys, baseline demographics, clinical characteristics, and treatment patterns were analyzed descriptively in self-reported preMeno pts with ABC. Results: At the data cutoff of May 20, 2020, 1208 pts were enrolled; 134 (11.1%) from 61 sites were preMeno, of whom 14.2% completed ≥6 months of PAL treatment. Among 134 preMeno pts (74.6%) who received first-line (1L) therapy, 69.0% received PAL+letrozole (LET) or anastrozole, 28.0% PAL+fulvestrant, and 3.0% PAL+exemestane. Median disease-free interval was 39.3 (range: 0 to 236) months; median treatment-free interval was 14.8 (-3 to 134) months. Of 34 pts (25.4%) who received PAL as second or later line (≥2L), 23.8% previously received hormonal therapy, 28.6% chemotherapy, and 14.3% both. The majority of pts (96.27%) initiated PAL at 125 mg regardless of line of therapy (Table). During the first PAL treatment cycle, 2.9% of all preMeno pts, 1% of 1L pts, and 8.8% of ≥2L pts had a dose reduction; 8.2%, 9%, and 5.9%, respectively, had an interruption. Dose reductions/interruptions peaked in cycle 2 (11.9%/15.7%); 56.67% of these modifications were due to adverse events. Conclusions: PAL is routinely prescribed in clinical practice for preMeno women with HR+/HER2- ABC. The majority of preMeno pts in this real-world dataset received PAL+LET as 1L ABC treatment; PAL was primarily initiated at the recommended dose (125 mg) and was well tolerated with few dose modifications required. Clinical trial identification: Pfizer (NCT03280303) Table.CharacteristicFirst-Line Pre/Perimenopausal Patients (n=100)Second or Later Line Pre/Perimenopausal Patients (n=34)Pre/Perimenopausal Patients (N=134)Age at study enrollment, yMedian (range)44 (22-61)42.5 (27-58)44 (22-61)Distribution, n (%)<4032 (32.0)12 (35.3)44 (32.8)40–5045 (45.0)17 (50.0)62 (46.3)51–6923 (23.0)5 (14.7)28 (20.9)Race, n (%)White73 (73.0)26 (76.5)99 (73.9)Black or African American16 (16.0)4 (11.8)20 (14.9)Asian1 (1.0)1 (2.9)2 (1.5)Native Hawaiian or other Pacific Islander2 (2.0)0 (0.0)2 (1.5)American Indian or Alaska Native1 (1.0)0 (0.0)1 (0.7)Other3 (3.0)2 (5.9)5 (3.7)Not reported because of confidentiality regulations4 (4.0)1 (2.9)5 (3.7)Hispanic/Latino ethnicity, n (%)10 (10.0)3 (8.8)13 (9.7)Disease status, n (%)Visceral35 (35.0)13 (38.2)48 (35.8)Nonvisceral61 (61.0)17 (50.0)78 (58.2)Not reported4 (4.0)4 (11.8)8 (6.0)Bone metastases at mBC diagnosis, among patients with metastatic (stage IV) disease at study enrollment, n (%)Bone only40 (40)8 (23.5)48 (35.8)Bone plus other metastases32 (32)13 (38.2)45 (33.6)Disposition of patient ABC/mBC diagnosis at study at study enrollment, n (%)Recurrent from earlier stage (Stage 0-III)72 (72.0)18 (52.9)90 (67.2)De novo (Newly diagnosed Stage IV at enrollment)26 (26.0)15 (44.1)41 (30.6)Not reported2 (2.0)1 (2.9)3 (2.2)ECOG performance status at study enrollment (N, %)041 (41)15 (44.1)56 (41.8)126 (26)7 (20.6)33 (24.6)28 (8)3 (8.8)11 (8.2)32 (2)0 (0)2 (1.5)Not reported23 (23)9 (26.5)32 (23.9)Starting dose, first cycle of PAL treatment n (%)125 mg96 (96.0)33 (97.1)129 (96.3)100 mg2 (2.0)1 (2.9)3 (2.2)75 mg2 (2.0)0 (0.0)2 (1.5)Reason for first cycle starting dose <125 mg, n (%)Patient preference0 (0.0)1 (100)1 (25.0)Other3 (100)0 (0.0)3 (75.0) Citation Format: Meghan S Karuturi, Adnan Garrett, Joanne L Blum, Jay Anderson, Erin Jepsen, Timothy Pluard, Thomas Stanton, Kenneth Manning, Joseph C Cappelleri, Faith Beery, Yao Wang, Debu Tripathy. Pre/perimenopausal (preMeno) women receiving palbociclib (PAL) for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC) in a real-world setting: Treatment patterns from POLARIS [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 PS7-19.

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Novel Therapies in Routine Clinical Practice in Germany

Management of Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Treated with Novel Therapies in Routine Clinical Practice in Germany

MONARCH 2: Subgroup analysis of patients receiving abemaciclib + fulvestrant as first- and second-line therapy for HR+, HER2- advanced breast cancer.

1061 Background: In MONARCH 2 (M2), abemaciclib (A), an oral selective cyclin dependent kinase 4 & 6 inhibitor, + fulvestrant (F) demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) compared to placebo (P) + F in hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer (ABC). Numerically more pronounced PFS & OS improvement was noted in subgroups (Sub) with visceral (V) disease and primary endocrine resistance. Here we report efficacy data for M2 with respect to 1L and 2L Sub (last line of endocrine therapy [ET] in (neo)adjuvant and metastatic setting, respectively). Methods: M2 (NCT02107703) was a global, randomized, double-blind Phase 3 trial of A+ F (N = 446) or P + F (N = 223) in women with ET resistant (ETR) HR+, HER2- ABC regardless of menopausal status. Patients (pts) were stratified by site of metastasis (V, bone-only, or other) and resistance to prior ET (primary vs secondary). Exploratory Sub analyses of PFS and OS were conducted among pts in the ITT population with 1L vs 2L. Hazard ratios (HR) were estimated using Cox models with a test of interactions of Sub with treatment performed. Results: At data cut-off (June 20th, 2019), the effect of A + F vs P + F was consistent across 1L (N = 265/133) and 2L (N = 170/86) Sub, with no statistically significant interaction for PFS (p = 0.341) or OS (p = 0.265). For 1L pts, improvements in PFS (HR: 0.57; 95% CI:0.45, 0.73) and OS (HR: 0.85; 95% CI:0.64, 1.14) were observed. Similar efficacy results were observed for 2L pts (PFS: HR: 0.48; [95% CI: 0.36, 0.64]; OS HR: 0.66 [95% CI: 0.46, 0.94]). The numerically largest effects in the 1L population were noted in pts with less favorable prognostic factors such as primary ETR (PFS: HR 0.40 [95% CI: 0.26, 0.63]; OS: HR 0.58 [95% CI:0.35, 0.97]) and V disease (PFS: HR 0.54 [95% CI: 0.39, 0.73]; OS: HR 0.82 [95% CI: 0.57, 1.17]). Conclusions: The statistically significant benefit observed in the M2 study was observed across 1L and 2L patients. In 1L patients (A+F Arm), improvements were observed for PFS and OS with the most pronounced effects noted in patients with less favorable prognostic factors. Clinical trial information: NCT02107703 .

Real-world outcomes in patients (pts) with metastatic urothelial carcinoma (mUC) who received first- or second-line immunotherapies (IO) in the United States (US).

457 Background: Benefit of IO (PD1 and PD-L1 inhibitors) for mUC was observed in clinical trials but real-world evidence for benefit and clinical outcomes is limited. Methods: This was a retrospective study of adult pts with mUC who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2019 in the US Oncology Network (USON), a network of community oncology practices. Descriptive and Kaplan-Meier analyses to evaluate baseline characteristics, treatment patterns and clinical outcomes were conducted using data from USON’s electronic heath record. Results: Among 393 pts in the 1L cohort, median (range) age at IO initiation was 77 (42, 90+), 74% were male, 69% were White, and 19.1% and 4.1% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 366 pts in the 2L cohort, median (range) age at IO initiation was 70 (29, 90+), 74% were male, 71% were White, and 19.7% and 1.4% had ECOG PS 2 and 3, respectively. Median (range) follow-up durations from IO initiation were 4.2 (0, 34.1; 1L cohort) and 4.1 (0, 31.3; 2L cohort) months (mo), during which time 43.1% (1L cohort) and 44.4% (2L cohort) of pts died. Median overall survival (OS) from IO initiation (95% confidence interval [CI]) was 10.6 (9.7, 13.2) mo for the 1L cohort and 9.4 (7.1, 11.5) mo for the 2L cohort; 1-year survival probabilities (95% CI) were 46.6% (40.1%, 52.8%; 1L cohort) and 43.4% (36.8%, 49.8%; 2L cohort). By the end of the follow-up, 48.1% of 1L pts and 47.8% of 2L pts were alive and did not advance to next line of therapy, and 13.5% of 1L and 13.4% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.6 (2.1, 2.9) and 2.8 (2.2, 3.5) mo for the 1L and 2L cohorts, respectively; 6-mo ongoing treatment probabilities (95% CI) were 26.6% (22.2%, 31.2%; 1L cohort) and 31.4% (26.4%, 36.4%; 2L cohort). Conclusions: OS of pts in the real world receiving 1L and 2L IO appears consistent with clinical trial results, although survival follow-up is limited. A minority of pts received post-IO therapy. Future research should examine influence of pt characteristics and PD-L1 expression on treatment choice and outcomes.

Treatment Patterns in Patients (pts) with Refractory/Relapsed Multiple Myeloma (RRMM) in Germany between 2016 and 2018

Treatment Patterns in Patients (pts) with Refractory/Relapsed Multiple Myeloma (RRMM) in Germany between 2016 and 2018

901O - EV-103: Initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma

901O - EV-103: Initial results of enfortumab vedotin plus pembrolizumab for locally advanced or metastatic urothelial carcinoma

PF408 DASFREE 2‐YEAR UPDATE: DASATINIB DISCONTINUATION IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA IN CHRONIC PHASE (CML‐CP) AND DEEP MOLECULAR RESPONSE (DMR)

Background:Treatment‐free remission (TFR) is a potential treatment goal for pts with CML‐CP. Sustained TFR has previously been reported for pts enrolled in the DASFREE trial (CA180406/NCT01850004), in which a 48% rate of relapse‐free survival was observed at 18 mo after dasatinib discontinuation (Shah Blood 2018). Here we report results for pts in DASFREE with a minimum of 2 y of follow‐up.Aims:To assess the durability of TFR at 2 y after discontinuing dasatinib treatment in pts with CML‐CP and dasatinib‐induced DMR.Methods:DASFREE is an open‐label, single‐arm phase 2 study in adult pts with CML‐CP on first‐line (1L) or subsequent‐line (≥2L) dasatinib for ≥2 y and with DMR (MR4.5; BCR‐ABL1 ≤0.0032% on the International Scale [IS]). MR4.5 was confirmed at a local lab for ≥1 y prior to enrollment and confirmed at a central lab twice within 3 mo prior to dasatinib discontinuation. BCR‐ABL1 was monitored centrally every mo after discontinuation in the 1st y and every 3 mo thereafter. If major molecular response (MMR; BCR‐ABL1 ≤0.1% IS) was lost, pts resumed dasatinib at their previous dose. The primary endpoint was the rate of MMR at 12 mo after discontinuation without restarting dasatinib. Key secondary endpoints include event‐free survival (EFS; survival with no loss of MMR), rate of transformation to accelerated phase/blast crisis (AP/BC), progression‐free survival (PFS; survival without progression to AP/BC), and overall survival. Key exploratory analyses include the frequency of adverse events (AEs) on and off treatment.Results:Pt characteristics were previously reported; briefly, 37 pts (44%) discontinued 1L dasatinib and 47 pts (56%) discontinued ≥2L dasatinib (Shah Blood 2018). To date, 11 pts (13%) have discontinued the study (2 off‐treatment; 9 after restarting dasatinib). In total, 46 pts lost MMR (1 pt lost MMR at mo 39 and had not restarted therapy at the time of this analysis) after a median of 4 mo (range 1–39) after discontinuation. Of the 46 pts who lost MMR, 45 (98%) restarted on dasatinib; 44 of 45 (98%) regained MMR after a median of 2 mo (range 1–4) and 43 (96%) regained MR4.5 after a median of 3 mo (range 2–18) (Figure). At 2 y, EFS was 46% (95% confidence interval [CI] 36, 57) in all pts, 51% (95% CI 35, 67) in 1L pts, and 42% (95% CI 28, 57) in ≥2L pts. PFS at 2 y was 99% (95% CI 96, 100) in all pts (there was 1 death unrelated to CML). No pts transformed to AP/BC. Time on prior treatment (regardless of line of dasatinib) was 65 mo for pts who lost MMR (n = 19) and 73 mo for pts who maintained MMR (n = 18). A univariate analysis revealed statistically significant associations between EFS and older age (hazard ratio [HR] 2.722; 95% CI 1.126, 6.578; P = 0.0261) and prior 1L therapy (HR 0.381; 95% CI 0.162, 0.893; P = 0.0265). All AEs observed thus far in DASFREE have been consistent with the known safety profile of dasatinib. There were 2 additional withdrawal events (in the same pts) at this follow‐up.Summary/Conclusion:Extended follow‐up results from DASFREE continue to support the feasibility of TFR in pts with CML‐CP who achieve stable DMR with dasatinib. The observed durability of TFR at 2 y (with 46% of all pts maintaining EFS) provides clinically relevant information for many pts considering TFR with dasatinib in the 1L and beyond. Lastly, no new pts experienced withdrawal events.image

Real-world outcomes of metastatic urothelial carcinoma (mUC) patients (pts) treated with first or second-line immunotherapies (IO) in the United States (US).

e16025 Background: While clinical trials have affirmed benefit of IO for mUC, limited real-world evidence exists to describe the current treatment landscape and clinical outcomes. This study evaluated these trends in a network of community oncology practices, the US Oncology Network (USON). Methods: This was a retrospective study of adult mUC pts who initiated IO regardless of PD-L1 expression in the first- (1L cohort) or second-line (2L cohort) setting between 5/1/2016-1/31/2018. Using data from USON’s electronic heath record, descriptive and Kaplan-Meier analyses were conducted to evaluate baseline characteristics, treatment patterns and clinical outcomes. Results: Among the 254 pts in the 1L cohort, median (range) age at IO initiation was 74 (42, 90+), 71% were male, 77% were Caucasian, and 18.1% and 5.9% had ECOG performance status (PS) 2 and 3/4, respectively. Among the 179 pts in the 2L cohort, median (range) age at IO initiation was 71 (29, 90+), 76% were male, 76% were Caucasian and 20.7% and 2.2% had ECOG PS 2 and 3/4, respectively. Nearly all pts received IO monotherapy. Median (range) follow-up durations from IO initiation were 4.3 (0, 22; 1L cohort) and 3.6 (0, 19; 2L cohort) months (mo), during which time 39% (1L cohort) and 37% (2L cohort) of pts died. Median overall survival (95% confidence interval [CI]) was 9.9 (7.5, 15.7) mo for the 1L IO cohort and 8.3 (6.4, not reached) mo for the 2L IO cohort. Six-mo survival probabilities (95% CI) were 61.6% (54.5%, 67.9%; 1L cohort) and 60.7% (51.4%, 68.8%; 2L cohort). In total, 52.8% of 1L pts and 53.6% of 2L pts were alive and did not advance to next line of therapy, and 11% of 1L and 13% of 2L cohort pts advanced to the next line of therapy. Median (95% CI) treatment durations were 2.3 (1.9, 3.0) and 3.3 (2.7, 3.9) mos for the 1L and 2L cohorts, respectively. Six-mo ongoing treatment probabilities (95% CI) were 28.9% (23.3%, 34.7%; 1L cohort) and 34.0% (26.1%, 42.1%; 2L cohort). Conclusions: Outcomes of real-world mUC pts receiving IO were as expected, with majority of pts alive and a small minority receiving post-IO therapy. Future research should examine how pt and tumor (PD-L1 expression) characteristics influence treatment and outcomes.

Sequencing chemotherapy and immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (UC): Meet-Uro1 study.

e16013 Background: Several ICI are now approved in different therapeutic settings of metastatic UC. The identification of the optimal therapeutic sequence that includes standard chemotherapy (CT) use is a key objective of further research, mainly in the first-line (1L) setting. In this study, we analyzed the pathways of treatment post-ICI and focused on the effects of CT post-ICI in both 1L and salvage-line (≥2L) therapy of metastatic UC. Methods: Data from 15 Italian centers were collected. Patients (pts) should have received ICI in any line of treatment for metastatic UC and have experienced a disease progression (PD) according to RECIST 1.1. Cox regression analyses were performed within the subgroups, and adjusted Kaplan-Meier curves analyzed the progression-free survival (PFS) and overall survival (OS) post-ICI PD, according to the treatment line. Results: 278 pts (79 in 1L; 199 ≥2L) were analyzed. In total, after ICI, pts were treated with CT (N = 69), ICI beyond PD (N = 20) or no treatment (N = 189). Features associated with no therapy post-ICI were rapid PD on ICI (p < 0.001) and number of metastatic sites (p = 0.002). The objective response (OR) to CT post-ICI was 23.1% in 1L, and 18.5% in ≥2L. Median PFS was 5 months (m) in 1L and 3m ≥2L, median OS on CT was 13m in 1L and 9m ≥2L. Post-ICI CT was not significantly associated with improved OS in 1L on multivariable analyses (MVA): HR: 0.43 (95%CI: 0.15-1.23), but it was significant in MVA in ≥2L pts (HR: 0.22, 95%CI: 0.10-0.48). The type of previous ICI (combination-ICI vs single-agent ICI, p = 0.789), as well as the OR to previous ICI (p = 0.871) had no effect on OS with sequential CT on MVA. In the total population adjusted by line, median OS post-CT was 17m (range 15-NA), and with ICI beyond PD was 8m (6-NA) (p < 0.001). Conclusions: This large multicentric appraisal indicated that CT post-salvage ICI is endowed with similar activity and efficacy compared to ICI-naïve pts. Conversely, CT administered post-ICI in 1L determined less responses and was not significant on MVA. These effects are likely determined by the inability to rescue pts with rapidly aggressive disease. Shifting to salvage CT at the time of PD on ICI remains the preferable option in all suitable pts.

Alpelisib (ALP) with fulvestrant (FUL) in patients (pts) with PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC): Primary or secondary resistance to prior endocrine therapy (ET) in the SOLAR-1 trial.

1038 Background: A contributor to ETR, phosphatidylinositol 3-kinase (PI3K) pathway hyperactivation can result from mutations to PIK3CA; ~40% of pts with HR+, HER2– ABC exhibit tumors with this mutation. Use of the oral α-specific PI3K inhibitor ALP + FUL significantly improved progression-free survival (PFS) in pts with a PIK3CA mutation (HR 0.65; 95% CI, 0.50-0.85; P<0.001) in SOLAR-1, which included both ET sensitive (ETS) and ETR pts (Table). ETS pts were later excluded by a protocol amendment. ETR was further defined as primary (1R) or secondary (2R) per ESMO criteria in both 1L and 2L pts. This subgroup analysis evaluated pts with a PIK3CA mutation based on tx line and endocrine status. Methods: SOLAR-1 was a phase 3, randomized, double-blind study of ALP 300 mg QD or PBO Q28d + FUL 500 mg Q28d + C1d15 in men and postmenopausal women with HR+, HER2– ABC whose disease progressed on/after an aromatase inhibitor. PFS was estimated by Kaplan-Meier method and median PFS (mPFS) presented by tx arm. A stratified Cox proportional hazards model estimated HR and 2-sided 95% CI. Results: Of 341 pts in the PIK3CA mutant cohort, 39 (11%) were ETS; 302 (89%) were ETR. mPFS in the ALP vs PBO arms was 22.1 vs 19.1 mo (HR 0.87; 95% CI, 0.35-2.17) for ETS pts and 9.4 vs 4.2 mo (HR 0.64; 95% CI, 0.48-0.84) for ETR pts. For ETR pts, mPFS for 1L (n=138) was 9.0 vs 4.7 mo (HR 0.69; 95% CI, 0.46-1.05) and for 2L (n=161) was 10.9 vs 3.7 mo (HR 0.61; 95% CI, 0.42-0.89). Conclusions: In SOLAR-1, mPFS was improved with ALP + FUL vs PBO + FUL across ETR pts in 1L and 2L. Representation of ETS pts was low in SOLAR-1, which included more ETR pts. Analysis of the PI3K pathway in ETS pts is warranted in future studies. Clinical trial information: NCT02437318. [Table: see text]

Pomalidomide + Bortezomib + Low-Dose Dexamethasone Vs Bortezomib + Low-Dose Dexamethasone As Second-Line Treatment in Patients with Lenalidomide-Pretreated Multiple Myeloma: A Subgroup Analysis of the Phase 3 Optimismm Trial

Pomalidomide + Bortezomib + Low-Dose Dexamethasone Vs Bortezomib + Low-Dose Dexamethasone As Second-Line Treatment in Patients with Lenalidomide-Pretreated Multiple Myeloma: A Subgroup Analysis of the Phase 3 Optimismm Trial

Dosing Patterns of Dasatinib Use in Simplicity, an Observational Study in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients (pts) in Routine Clinical Practice

Introduction: Treatment dosing patterns have not been well documented among dasatinib-treated CP-CML pts outside of clinical trials. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML adult pts in routine clinical practice receiving tyrosine kinase inhibitors (TKI) since 2010 in the US and Europe, exploring TKI use and management patterns in clinical practice. This analysis reports on dosing patterns of dasatinib and explores potential predictors of dose reductions.Methods: Only pts enrolled in the SIMPLICITY observational study who received first-line (1L) and second-line (2L) dasatinib once daily (n=417) were reviewed to determine dosing patterns. Eleven pts were excluded from the analysis because they were not on a dasatinib once-daily regimen. Longitudinal data were used to determine dose changes. Results are presented according to the first change in dose. No restrictions or instructions regarding dosing were required per enrollment. Results are presented descriptively. Statistical comparisons were made using t-tests and the Mann-Whitney U test for continuous variables and chi-square for categorical variables. Logistic regression models were used to identify factors associated with dose reduction.Results: Of the 406 pts treated with 1L dasatinib (QD), 374 (92.1%) started at 100 mg (Table 1); 318 (78%) remained on dasatinib at Year 1 and 259 (63.8%) at Year 2. The majority (64.4%) remaining on100 mg. Median follow-up was 59 months (IQR: 49, 61). Of the 25 (6.2%) pts who started on <100 mg, 12 started on 50 mg and 8 on 70 mg. Of the 7 (1.7%) who started at >100 mg, 6 started on 140 mg. Median age at start of 1L TKI differed between pts who started on 100 mg (55.2 yrs), <100 mg (73.7 yrs), and >100 mg (49.2 yrs; p<0.0001; Table 1). EU pts were more likely to start with a lower dose vs US pts (p<0.001): with 84.4% vs 95.0% starting on 100 mg; 13.8% vs 3.4% on <100 mg and 1.8% vs 1.7% on >100 mg, respectively. Of the 374 pts who started 1L dasatinib at 100 mg, 133 (35.6%) changed dose; 124 (33.2%) pts received a dose reduction and nine (2.4%) a dose increase (Table 1). Median time to dose reduction was 4.7 months (IQR: 1.5, 19.5): 51.6% pts (n=64) experienced a dose reduction in the first 6 months; 12.9% (n=16) between 6-12 months; 15.3% (n=19) between 12-24 months and 20.2% (n=25) after 24 months. Pts remained on a reduced dose for a median of 47.6 months (Table 2). Among the 33% that experienced dose reductions, the primary reasons for dose reduction were adverse events (63.7%; n=79), side effect/clinical complication (9.7%; n=12) and other clinical decisions, including stable MR4.5 (11.3%; n=9.7%; Table 1). Age (mean, p=0.003; median p=0.001) and male gender (p=0.02) at baseline were associated with dose reduction. Multivariate logistic regression analysis of the 1L dasatinib population, adjusted for covariates revealed that older age at start of 1L TKI (p=0.004) and fatigue at baseline (poorer performance status; p=0.02), were strong predictors for dose reduction (Table 1). Gender was a weak predictor for dose reduction (p=0.06; Table 1). Of the 202 pts receiving 2L dasatinib (QD), 25 (12.4%) started at <100 mg. Median follow-up was 57.4 months (IQR: 46.5, 60.8). Of these, 12 (48%) pts started on 50 mg and 10 (40%) on 70 mg. Of the 166 pts who started 2L dasatinib at 100 mg, 41 (24.7%) changed dose. Thirty-nine pts received a dose reduction (50 mg, n=18 [46.2%]; 70 mg, n=6 [15.4%]) and two a dose increase. Among the 23% receiving a dose reduction, intolerance (n=27; 69.2%) and other clinical decisions, including stable MR4.5 (n=6; 15.4%) were the primary reasons for dose reduction. There was a non-significant difference in median age between pts who started 2L dasatinib at 100 mg, <100 mg, and >100 mg, but otherwise they were similar in terms of other baseline characteristics.Conclusions: Now that long-term survival has been achieved in pts with CML, the focus of clinical practice is shifting to dose optimization, with the goal of maintaining response while improving quality of life. Among the majority of pts who started dasatinib at 100 mg (QD) in 1L, 64.4% received only 100 mg; 33.1% received a dose reduction, and 2.4% received a dose increase; similar patterns were observed for 2L pts. Within the population experiencing a dose reduction, intolerance was the principal reason. Age at start of 1L TKI and fatigue in baseline (poorer performance status) were strong predictors of dose reduction, while gender was a weak predictor. [Display omitted] DisclosuresCortes:Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Arog: Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Chen:Bristol-Myers Squibb: Employment. Mauro:Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy, Research Funding; Takeda: Consultancy. Sen:ICON PLC: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment. Goldberg:COTA Inc.: Employment, Equity Ownership.

1214P - Establishing the need for immuno-oncology (IO) therapy (tx) in second-line (2L) small cell lung cancer (SCLC)

Background: 2L tx for SCLC is heavily dependent on 1L platinum (PT) response. NCCN guidelines recommend PT retreatment if recurrence is > 3-6 months post 1L PT; while alternative options should be considered for rapid relapse (topotecan [TOP] in 2L PT-resistant). In 2016, nivolumab (NIVO) +/- ipilimumab (IPI), were added to 2L NCCN guidelines. This study evaluates 2L SCLC patterns of care and outcomes and attempts to contextualize CheckMate 032 data by creating a matched real-world comparator. Methods: Adult SCLC pts receiving systemic tx from the Flatiron Health database were selected (01Jan2011-30Sep2017). Index date was SCLC diagnosis (dx). Pts were included if: not on clinical trial; no secondary malignancy within 3 years (y); no IO use; and ≥2 months (mo) of medical data on/after dx. PT sensitivity was based on a 90 day gap. Median, 1-y and 2-y overall survival (OS) by Kaplan-Meier was calculated from 2L initiation to death. Median duration of therapy (mDoT) was assessed. A matched 2L cohort was constructed using CheckMate 032 Inclusion/Exclusion criteria (I/E). Results: 2,056 pts initiated 1L tx (full cohort), of which 628 pts went on to 2L; 42% received TOP and 58% other txs. Within 2L, mean age was 65y; 69% were white, 51% were female, 98% had a smoking history and 95% were treated in the community. Of 2L pts, 68% had extensive and 27% had limited disease at dx. 372 were PT-sensitive and 231 pts were PT-resistant. Upon matching for CheckMate 032 I/E, 903 pts were identified of whom 254 initiated 2L. For the full and matched cohorts respectively, 2L mDoT for TOP was 2.0 mo (SD = 2.5) and 2.2 mo (SD = 2.7) and for other tx was 2.6 mo (SD = 2.2) and 2.8 mo (2.4). Median, 1-y and 2-y OS results for the full/ matched cohorts and CheckMate 032 are shown (Table).Table: 1214POverall survival from diagnosis and 2L initiation in Flatiron Health and CheckMate 032median OS, months [95%CI]1-year / 2-year survival (%)FULL COHORTFrom DiagnosisAll (N = 2056)11.6 [11.1,12.3]48.6/ 22.0Limited disease (n = 680)19.6 [18.0,21.5]71.9/ 42.3Extensive disease (n = 1,263)9.4 [8.9,9.9]35.2/ 10.5From Initiation of 2LAll (n = 628)4.2 [3.7,4.7]13.3/ 3.3PT-sensitive (n = 372)5.4 [4.4,6.2]15.9/ 4.2PT-refractory (n = 231)3.0 [2.6,3.6]9.1/ 2.9MATCHED COHORTFrom DiagnosisAll (N = 903)12.5 [11.5,14.3]47.0/ 26.4Limited disease (n = 348)23.8 [20.0,29.5]72.0/ 49.5Extensive disease (n = 507)9.8 [8.9,10.6]37.9/ 12.1From Initiation of 2LAll (n = 254)4.9 [4.0,6.2]14.6/ 3.8PT-sensitive (n = 158)6.3 [5.6,7.5]18.4/ 6.0PT-refractory (n = 90)2.7 [2.1,3.3]5.6/ 1.9CHECKMATE 032NIVO 3 mg/kg cohort (n = 98)4.4 [3.0–9.3]33/ NRNIVO 1 mg/kg + IPI 3 mg/kg (n = 61)7.7 [3.6–18.0]43/ NRNIVO 3 mg/kg + IPI 1 mg/kg (n = 54)6.0 [3.6–11.0]35/ NR*NR=not reported; PT=platinum; NIVO=nivolumab; IPI=ipilimumab Open table in a new tab *NR=not reported; PT=platinum; NIVO=nivolumab; IPI=ipilimumab Conclusions: This large retrospective data set highlighting 2L SCLC outcomes demonstrates poor survival in this setting underscoring the need for novel tx. Results from CheckMate 032 present IO as a potential option for SCLC pts. Editorial acknowledgement: This study was funded by Bristol-Myers Squibb, Inc. All authors contributed to and approved the presentation. Editorial assistance was provided by PAREXEL, funded by Bristol-Myers Squibb. Legal entity responsible for the study: Bristol-Myers Squibb. Funding: Bristol-Myers Squibb. Disclosure: L. Schwartzberg: Consultant: Bristol-Myers Squibb, Merck, Pfizer, Astra Zeneca, Amgen. J.R. Penrod, Y. Yuan, T. Gu, T.K. Le, P. Abraham, B. Korytowsky, G. Selvaggi: Employee, Stock ownership: Bristol-Myers Squibb.

Efficacy and safety of rovalpituzumab tesirine in patients With DLL3-expressing, ≥ 3rd line small cell lung cancer: Results from the phase 2 TRINITY study.

8507Background: Small cell lung cancer (SCLC) accounts for ~15% of lung cancer with no approved therapies in ≥ 3rd line (3L) patients (pts). In 3L pts, historical data demonstrate a median overall survival (mOS) of 4.7 mo and a best overall response of 18%; no historical data exist for objective response rate (ORR). Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting Delta-like 3 protein (DLL3), an atypical Notch ligand that is highly expressed in SCLC but not normal tissue. A Ph1 study showed that Rova-T has antitumor activity in pts with recurrent SCLC and high DLL3 expression, and a manageable safety profile. Methods: TRINITY was an open-label, single-arm, Ph2 study of Rova-T in adult pts with DLL3-expressing SCLC (NCT02674568). Eligibility: ≥ 2 prior systemic regimens including ≥ 1 platinum-based regimen; ECOG 0-1; stable CNS disease. Pts received 0.3 mg/kg Rova-T intravenously on Day 1 of a 6-week cycle for 2 cycles. DLL3-high (hi) pts had ≥ 75% tumor cells positive by immunohis...

Three fluoropyrimidine-based regimens in second-line therapy following nab-paclitaxel plus gemcitabine in metastatic pancreatic cancer: Efficacy and tolerance in clinical practice.

370 Background: Combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a valid first-line treatment (1L) in metastatic pancreatic adenocarcinoma (MPA) in patients (pts) with performance status (PS) of 0,1 or 2, but there is currently no standard second-line treatment (2L) after this new 1L option. We evaluated survival outcomes and tolerability of three usual fluoropyrimidine-based regimens: FOLFOX, FOLFIRI or FOLFIRI.3 (FOLFIRI1/3), and FOLFIRINOX after N+G failure in MPA pts. Methods: We prospectively identified 138 pts from 11 French centers who received 1L N+G for unresectable pancreatic adenocarcinoma. After disease progression or unacceptable toxicity, we excluded pts with locally advanced cancer, or who underwent secondary resection/chemoradiotherapy. Three subgroups of 2L chemotherapy were identified: FOLFOX, FOLFIRI1/3 and FOLFIRINOX regimens. Response was evaluated by RECIST criteria, progression-free survivals (PFS1, PFS2), and overall survival (OS1, OS2) were calculated using Kaplan-Meier method and compared with the Log-rank test. Results: 61 pts with MPA received a 2L. Persistent neuropathy was present in 27% of pts. Median age was 71.7 years [41-83]. PS was 0, 1 or 2. Median 1L duration, number of metastatic sites, PS, CA19.9, albumin, and bilirubin levels, and persistent neuropathy grade were statistically comparable between the 3 subgroups. Median OS for all 2L pts was 6.0 months [4-8]. Third line regimen was used in 32.8% of 2L pts without statistical significance between the subgroups. Main grade 3/4 adverse events reported were thrombocytopenia (18%), anemia (7.7%), neutropenia (21.4%) and nausea (5.4%). No toxic deaths occurred. Conclusions: This study suggests a clinical benefit and a manageable toxicity profile of 2L fluoropyrimidine-based regimens after N+G failure in patients with MPA, in particularly combined with irinotecan.[Table: see text]