Overall Survival In Pts Research Articles

90P Disease-free survival (DFS) as a predictor of overall survival (OS) in completely resected early stage non-small cell lung cancer (NSCLC)

Evidence based on clinical trials has shown a very good correlation between DFS and OS in completely resected NSCLC patients (pts) with adjuvant therapy. This study assessed the relationship between DFS and OS in real-world pts and disease burden associated with recurrence.

Survival outcomes of metastatic renal cell carcinoma (mRCC) with sarcomatoid differentiation (SD): A single-institutional experience and literature meta-analysis.

332 Background: Patients (pts) with mRCC with SD have unfavorable outcomes and poor prognosis due to aggressive tumor behavior. Chemotherapy and targeted treatment are often of little benefit. However, recent studies have shown a survival benefit of immunotherapy (IO). Here, we report survival outcomes of pts with mRCC with SD treated with first line IO or chemotherapy or targeted treatment. In addition we performed a meta-analysis of recent practice changing phase III, IO trials in mRCC. Methods: This retrospective survival analysis was performed in pts with mRCC with SD treated with IO or non-IO treatment at Princess Margaret Cancer Centre (PM), Toronto. Demographics, disease characteristics and survival outcomes were collected. Progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method (log-rank). PFS and OS hazard ratios (HR) were calculated using cox proportional hazards model. We identified the major, practice changing clinical trials that reported survival outcomes of mRCC with SD treated with IO and performed a random-effects meta-analysis of HR for PFS and OS. We compared these pooled results to our single institution experience. Results: We identified 474 pts diagnosed with mRCC at PM between 2002 and 2019. In total, 44 (9.3%) pts had mRCC with SD who were treated with IO or non-IO. Of these, 29 (65.9%) pts had pure SD and 15 (34.1%) pts had mixed rhabdoid and SD features. Median age was 59.6 years (36-78) and 33 (75%) were male. Overall, as per the IMDC score, 3(6.8%), 21(47.7%) and 20(45.5%) pts were categorized as good, intermediate, and poor risk, respectively. Eight (18.2%) pts were treated with IO as first line of treatment, and 36 (81.8%) pts received non-IO. With a median follow up of 64.8 months (range, 45.7-83.8 months), the median OS for the whole mRCC with SD cohort was 15.6 months (95% CI: 8.6-22.5). The median OS in all pts treated with IO vs non-IO was not reached vs 10.3 months (95%CI: 1.49-19.1 months; p = 0.005), respectively. The HR for OS was 0.1 (95%CI: 0.01-0.78; p = 0.023) favoring IO receipt. The median PFS in all pts treated with IO vs non-IO was 24 months (95%CI: non-estimable) vs 5.4 months (95%CI: 2.9-7.8 months; p = 0.021), respectively. The HR for PFS was 0.3 (95%CI: 0.11-0.89; p = 0.03) favoring IO receipt. We identified through meta-analysis five phase III clinical trials reporting PFS and OS in pts with mRCC with SD who received IO. The overall HR for OS and PFS for the total cohort were 0.55 (95%CI: 0.41-0.74), and 0.53 (95%CI: 0.42-0.67), respectively. Conclusions: Our meta-analysis has confirmed the benefit of IO agents in mRCC with SD. While the numbers included in this retrospective review were small, they have provided real world corroboration of the trial findings. Pts with mRCC and SD benefit from IO treatment, which should be considered the standard of care for these patients.

Overall survival (OS) after progression on first novel hormonal therapy (NHT) in patients (pts) with metastatic castration-sensitive versus castration-resistant prostate cancer (mCSPC versus mCRPC).

121 Background: Novel hormonal therapy (NHT) i.e. novel androgen receptor or androgen synthesis inhibitors have been approved for treatment of pts with mCSPC and mCRPC based on improved OS. However, OS of patients after progression on first-line NHT for mCSPC is not well characterized. It is currently unknown whether the OS in pts “after” progression on first-line NHT in mCSPC versus mCRPC is significantly different. Herein, our objective was to assess OS after disease progression on NHT given as the first-line therapy in the mCSPC vs first-line therapy in mCRPC setting. Methods: In this IRB-approved study, patient-level data were collected retrospectively, only those treated with NHT as first-line therapy for mCSPC or mCRPC were included. For patients receiving NHT in the mCRPC setting, no prior NHT was allowed in the mCSPC setting. Median overall survival and hazard ratios were determined by Kaplan-Meier analysis. Results: A total of 173 pts (45 mCSPC and 128 mCRPC) were eligible and included in the analysis. Median OS in the mCSPC versus mCRPC were similar: 23 vs. 17 months, hazard ratio: 0.9855, (95% CI: 0.6225 – 1.560, P=0.951). See the table. Conclusions: These results suggest median OS is similar after progression on one NHT whether given in the first-line mCSPC or first-line mCRPC setting. These data have implications on patient counseling and prognostication as well as the design of clinical trials in patients experiencing disease progression on an NHT. These hypothesis generating data need external validation.[Table: see text]

Blood biomarkers and association with clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC): prespecified longitudinal analysis from the ACIS study of apalutamide (APA) or placebo combined with abiraterone acetate plus prednisone (AAP).

142 Background: In ACIS, APA + AAP improved radiographic progression-free survival in mCRPC vs AAP; difference in overall survival (OS) was not statistically significant. We report a prespecified analysis of androgen receptor (AR) or non-AR genomic/transcriptional aberrations, known to be associated with poor prognosis, and their associations with OS in patients (pts) with mCRPC. Methods: Circulating tumor (ct)DNA and aberrations in 17 PC-relevant genes were assessed using next-generation sequencing at baseline (BL; n = 197) and at end of study treatment (EOST; n = 140) (biomarker population). ctDNA was summarized qualitatively; genomic aberrations were normalized by ctDNA detection. AR splice variant version 7 (ARv7) was detected by quantitative RT-PCR. Cox proportional hazards model assessed association of OS with biomarkers in univariate/multivariate analyses overall and in pts receiving subsequent treatment (tx). Results: BL characteristics of biomarker and total study populations were similar. From BL to EOST: ctDNA detection did not differ (123/196 [63%] to 92/140 [66%], p=0.6); significant increases occurred in ARv7, AR mutations, and any AR aberration (Table). Prevalence of aberrations in PI3K and homologous recombination repair (HRR) pathways did not change from BL to EOST (40/123 [33%] to 34/92 [37%], p=0.5 and 18/123 [15%] to 14/92 [15%], p>0.9, respectively). Worse OS was associated with ctDNA detection or HRR pathway inactivation at BL (HR, 2.5 or 2.2; all p < 0.001) or presence of ctDNA, ARv7, AR amplification or inactivation of TP53, RB1, or RB1/TP35 pathway at EOST (2.2, p < 0.001; 2.1, p < 0.001; 2.6, p < 0.001; 1.5, p < 0.05; 1.7, p < 0.05; 2.1, p < 0.001, respectively) in univariate analyses. EOST ARv7, AR amplification, and inactivation of RB1, TP53, or RB1/TP53 pathway was associated with worse OS in pts receiving subsequent tx. Detection of ctDNA and RB1 inactivation at BL and RB1/TP53 pathway inactivation at EOST was strongly associated with worse OS (2.1, 3.3, 2.9, respectively, all p < 0.01) in multivariate analyses. Conclusions: In ACIS, AAP or APA + AAP tx was associated with increased AR mutations and ARv7 expression. Detection of ctDNA and select AR/non-AR aberrations may predict poor survival in mCRPC. These markers may be used to improve tx selection following confirmation of their predictive value. Clinical trial information: NCT02257736. [Table: see text]

Overall survival with darolutamide versus placebo in combination with androgen-deprivation therapy and docetaxel for metastatic hormone-sensitive prostate cancer in the phase 3 ARASENS trial.

13 Background: Darolutamide (DARO) is a structurally distinct and highly potent androgen receptor inhibitor that demonstrated improved overall survival (OS) and metastasis-free survival vs placebo (PBO) and a low incidence of treatment-emergent adverse events (TEAEs) in patients (pts) with nonmetastatic castration-resistant prostate cancer (CRPC). We investigated whether DARO in combination with standard androgen-deprivation therapy (ADT) + docetaxel would increase OS in pts with metastatic hormone-sensitive prostate cancer (mHSPC) in the ARASENS study (NCT02799602). Methods: This international, double-blind, phase 3 study enrolled pts with mHSPC and ECOG PS 0/1 who were randomized 1:1 to DARO 600 mg twice daily or matching PBO in addition to ADT + docetaxel. Randomization was stratified by extent of disease according to TNM (M1a vs M1b vs M1c) and alkaline phosphatase levels ( < vs ≥ upper limit of normal). The primary endpoint was OS. Secondary efficacy endpoints included time to CRPC, time to pain progression, time to first symptomatic skeletal event (SSE), and time to initiation of subsequent systemic antineoplastic therapies. Safety was also assessed. Results: From Nov 2016 to June 2018, 1306 pts were randomized, 651 to DARO and 655 to PBO, in combination with ADT + docetaxel. Median age was 67 y in both arms. At the primary data cutoff (Oct 25, 2021), DARO significantly decreased the risk of death by 32.5% vs PBO (HR 0.675, 95% CI 0.568–0.801; P < 0.0001). The significant improvement in OS was observed even though substantially more pts received subsequent life-prolonging systemic antineoplastic therapy in the PBO arm (75.6%) vs the DARO arm (56.8%). The significant OS benefit was consistent across prespecified subgroups. In addition, DARO significantly delayed time to CRPC versus PBO (HR 0.357, 95% CI 0.302–0.421; P < 0.0001). Time to pain progression was also significantly longer with DARO vs PBO (HR, 0.792, 95% CI 0.660–0.950; P= 0.0058), as were time to first SSE and time to initiation of subsequent systemic antineoplastic therapy. TEAEs were similar between treatment arms, and the incidences of the most common TEAEs (≥10%) were highest during the overlapping docetaxel treatment period for both arms, with grade 3/4 TEAEs of 66.1% for DARO and 63.5%for PBO, mainly due to neutropenia (33.7% vs 34.2%, respectively). TEAEs led to treatment discontinuation in 13.5% of pts in the DARO arm and 10.6% of pts in the PBO arm. Conclusions: In pts with mHSPC, early treatment combining DARO with ADT + docetaxel significantly increased OS and improved key secondary endpoints vs ADT + docetaxel alone. The incidence of TEAEs was similar in the two treatment arms. Clinical trial information: NCT02799602.

Clinical and molecular features of low prostate-specific membrane antigen (PSMA) expression in patients (pts) with metastatic castration resistant prostate cancer (mCRPC).

167 Background: Low PSMA uptake on positron-emission tomography is seen in up to 30% of mCRPC pts and represents a clinically distinct subgroup with adverse outcomes. We assessed transcriptional and clinical features associated with low PSMA ( FOLH1) gene expression in mCRPC. Methods: A retrospective analysis of mCRPC biopsy samples with RNA-seq data was undertaken. Normalized FOLH1 expression was compared across histologic subtypes and sites of disease. We assessed the association between FOLH1 expression, selected androgen receptor (AR) target genes, master regulators of neuroendocrine differentiation, and previously validated AR activity and treatment-associated small cell neuroendocrine carcinoma (t-SCNC) transcriptional signature scores using Pearson correlations. Associations between FOLH1 and both PSA50 response to subsequent AR-targeted therapy and overall survival (OS) were examined by logistic regression and Cox proportional hazard models, respectively. Results: Samples from 97 pts were identified, of which 18% harbored t-SCNC histology. 45% of pts had visceral metastases at the time of biopsy, and 41% received subsequent AR-targeted therapy. Median FOLH1 expression was lower in pts with visceral metastases vs no visceral metastases (14.7 vs 15.6, p = 0.02) but was not significantly different across t-SCNC vs adenocarcinoma biopsies (14.3 vs 15.4, p = 0.13). FOLH1 expression was positively correlated with AR transcriptional activity and AR target genes, and negatively correlated with master regulators of neuroendocrine differentiation and t-SCNC transcriptional signature scores (Table). Low FOLH1 expression did not predict PSA50 response to subsequent AR-targeted therapy (OR 0.97, p = 0.8), but was associated with shorter OS on univariate analysis (HR 1.09, 95% CI 1.02-1.16, p=0.01). A post-hoc analysis revealed a trend towards decreased median OS in pts with FOLH1 expression <12 (7.5 vs 17.1 months, log-rank p = 0.06). Conclusions: In this retrospective analysis of mCRPC pts, low FOLH1 expression was associated with transcriptional features of t-SCNC, decreased AR activity, and shorter OS. These findings are hypothesis-generating and prospective validation is needed.[Table: see text]

Alliance A031902 (CASPAR): A randomized, phase (ph) 3 trial of enzalutamide with rucaparib/placebo as novel therapy in first-line metastatic castration-resistant prostate cancer (mCRPC).

TPS194 Background: Despite a growing number of treatment options for first line mCRPC, approximately 40% of patients (pts) have radiographic progression within the first year. Androgen receptor (AR) signaling inhibition increases genomic instability with double-strand DNA breaks & co-inhibition of AR & PARP induces synthetic lethality in multiple preclinical models. Homologous recombination repair (HRR) gene aberrations do not appear to be necessary for this synergy as demonstrated in a ph 2 clinical trial of abiraterone & olaparib where this combination improved radiographic progression-free survival (rPFS) in HRR-wild-type pts compared with abiraterone alone. A ph 1b trial has since shown that enzalutamide plus rucaparib has acceptable safety profile & no significant drug-drug interactions (S-DDI). Methods: CASPAR/A031902 (NCT04455750) is a ph 3 study in which 984 pts will be randomized 1:1 to enzalutamide plus rucaparib or placebo. HRR gene aberration is not required for enrollment. All pts will undergo next-generation targeted-exome sequencing from archival tumor tissue (new biopsy only required if no archival tissue available). Treatment will be continued until disease progression & crossover is not allowed. Key eligibility criteria are age ≥ 18 years, ECOG PS 0-2, biopsy-proven prostate adenocarcinoma, progressive (PSA or radiographic) disease per Prostate Cancer Working Group 3 guidelines, measurable or nonmeasurable disease per RECIST 1.1, no prior treatment for mCRPC (prior docetaxel, abiraterone, darolutamide, or apalutamide in non-mCRPC setting is allowed), no significant uncontrolled comorbidity, & no medications with S-DDI with enzalutamide/rucaparib. Hierarchical co-primary endpoints are rPFS & overall survival (OS). The OS analysis will be undertaken as a primary endpoint if the rPFS endpoint is met. For a one-sided logrank test with a type 1 error rate equal to 0.025, the study has 90% power to detect a hazard ratio (HR) of 0.71 in rPFS (median rPFS of 15 & 21 months in control & combination arms, respectively) & 80% power to detect an HR of 0.80 in OS (median OS of 32 & 40 months, respectively). Key secondary endpoints are rPFS & OS in pts with vs without pathogenic BRCA1, BRCA2, or PALB2 alterations; & differences in adverse events & quality of life (QOL) outcomes between the treatment arms. QOL assessments include Functional Assessment of Cancer Therapy–Prostate (FACT-P), Brief Pain Inventory Short Form (BPI-SF) & EQ-5D-5L. A key correlative endpoint is the sensitivity of ctDNA-based testing for alterations in HRR genes. Enrollment to CASPAR began in July 2021 & the study is available for participation to all US-NCTN sites with a projected enrollment of 3 years. Support: U10CA180821, U10CA180882, U24CA196171; U10CA180888; Clovis Oncology; http://acknowledgments.alliancefound.org Clinical trial information: NCT04455750.

Progression-free survival (PFS) and overall survival (OS) in patients (pts) with de-novo, high-volume metastatic castration-sensitive prostate cancer (dn-hv-mCSPC) undergoing intensified androgen deprivation therapy (ADT).

133 Background: In the PEACE-1 trial (Fizazi, ESMO 2021), in pts with dn-hv-mCSPC, the addition of abiraterone to ADT + docetaxel (triplet therapy arm) resulted in a median OS of 61 months (OS on ADT + docetaxel arm was 42 months). However, independent contribution of docetaxel to efficacy of ADT + abiraterone in the triplet therapy arm of PEACE-1 trial is not clear. Furthermore, the efficacy of an novel hormonal therapy (NHT) specifically in dn-hv-mCSPC population has not been reported (LATITUDE trial’s eligibility did not include volume status). Herein, our objective was to assess PFS and OS in a cohort of dn-hv-mCSPC pts undergoing intensified ADT with either NHT (i.e. novel androgen receptor or androgen synthesis inhibitors) or docetaxel. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: presence of dn-hv-mCSPC (hv per CHAARTED criteria) undergoing intensified ADT with either NHT or docetaxel started within 3 months of diagnosis. Study endpoints: PFS was calculated per PCWG-2 - defined PSA progression or radiographic progression or clinical progression whichever occurred first; OS was defined as start of therapy to date of death or censored at last follow-up. A multivariate analysis using the Cox proportional hazards (Cox-ph) model was used; the relationship between treatment intensification with both PFS and OS was assessed and adjusted for age at diagnosis, Gleason score, presence of visceral metastases, and PSA at baseline. Results: 85 pts with dn-hv-mCSPC were included: 45 received ADT + NHT; 40 received ADT + docetaxel. In the NHT vs docetaxel arms: median PFS were 23 vs 14 months; and median OS were 63 vs 36 months respectively. See the table for Cox-ph and adjusted co-variate results. Conclusions: We for the first-time report the real-world survival outcomes with ADT + NHT specifically in pts with dn-hv-mCSPC. In addition, in these hypothesis-generating data, the OS of pts with dn-hv-mCSPC undergoing ADT + NHT or ADT + docetaxel were similar to those in the triplet therapy arm or ADT + docetaxel arm of PEACE-1 trial respectively. A randomized trial in pts with dn-hv-mCSPC comparing ADT + NHT vs triplet therapy may better characterize the benefit of the docetaxel component in the triplet therapy.[Table: see text]

Incidence and clinical outcomes of HER2-altered bladder cancer (BC) patients (pts).

556 Background: Bladder cancer has one of the highest rates of human epidermal growth factor receptor 2 (HER2) alteration. Novel HER2-directed agents are being investigated in metastatic BC. We sought to define the incidence and clinical characteristics of HER2-altered BC across disease states. Methods: We retrospectively analyzed our single-institution, clinically annotated cohort of urothelial BC pts with available genomic profiling data (MSK-IMPACT). We quantified the prevalence of HER2 alterations, defined as driver mutation (based on OncoKB), and/or amplification, across BC disease states. We examined the association between HER2 alteration and disease progression and survival. The Kaplan-Meier method was used for time-to-event analyses. Results: A total of 1073 BC pts underwent MSK IMPACT profiling of tumor tissue derived from the following disease states: 36% (n = 380) non-muscle invasive (NMI)BC, 41% (n = 443) muscle invasive (MI)BC, and 23% (n = 250) (met)BC. At initial diagnosis, the median age was 67 years, 77% (n = 822) were male, 86% (n = 928) were white, and 66% (n = 710) were smokers. Overall, 16% (n = 177) of pts had any oncogenic HER2 alteration (Table), including 11% with a HER2 driver mutation and 7% with HER2 amplification The most frequent mutations were S310F (40%, n = 53) and S310Y (14%, n = 19). The rate of HER2 amplification was different among the three groups (p = 0.002), 9% in MIBC and metBC compared to 3% in NMIBC. Among 514 pts with NMIBC, the median time to progression (TTP) to MIBC or metBC was 111.6 months (95% Cl: 85.7-NR). Among NMIBC pts, TTP was significantly shorter for HER2-amplified (n = 17) vs. non-amplified (n = 497) (HR = 1.99, 95%CI: 1.05-3.76, p = 0.034, median 26 vs. 114 months). Among pts with metBC receiving frontline platinum-based chemotherapy (n = 143), the median overall survival (OS) was 25.3 months (95%CI: 18.5-33.9). OS was numerically higher in pts with any oncogenic HER2 alteration (n = 26) compared to wild-type (n = 117) (HR = 0.59, 95% Cl: 0.33-1.07, p = 0.082), though this difference was not statistically significant. The median OS for platinum-refractory metBC pts receiving 2nd line immunotherapy (n = 63) was 10.3 months (95%CI: 7.2-31.6), and the association between OS and HER2 alteration was not significant (HR = 0.57, 95%CI: 0.24-1.37, p = 0.2). Conclusions: HER2 amplification is more frequent in MIBC and metBC than in NMIBC. In NMIBC, HER2 amplification is associated with shorter TTP to MIBC or metBC. HER2 alteration in metBC is associated with a non-significant trend towards improved OS in frontline platinum-treated pts, though this analysis is limited by small sample size.[Table: see text]

Final overall survival analysis and organ-specific target lesion assessments with two-year follow-up in CheckMate 9ER: Nivolumab plus cabozantinib versus sunitinib for patients with advanced renal cell carcinoma.

350 Background: First-line nivolumab plus cabozantinib (N+C) demonstrated superiority over sunitinib (SUN) in the primary disclosure of the phase 3 CheckMate 9ER trial (NCT03141177; 10.6 months minimum follow-up; Choueiri TK et al. N Engl J Med 2021) in patients (pts) with advanced renal cell carcinoma (aRCC). Here, we report the preplanned final overall survival (OS) analysis with updated efficacy and safety in intent-to-treat (ITT) pts, and an exploratory assessment of target lesions by organ site after extended follow-up. Methods: Pts with aRCC (clear cell component) were randomized to N 240 mg every 2 weeks + C 40 mg once daily vs SUN 50 mg once daily (4 weeks of 6-week cycles). The primary endpoint was RECIST v1.1–defined progression-free survival (PFS) by blinded independent central review (BICR) in ITT pts; secondary endpoints included OS, objective response rate (ORR) by BICR, and safety. The preplanned final OS analysis was set to occur after observing 254 events. Maximal reduction of target lung, lymph node, kidney, and liver lesions were evaluated per BICR via post hoc exploratory analyses. Results: After 25.4 months minimum follow-up (median, 32.9 months) for OS in ITT pts, a total of 271 OS events occurred, and N+C continued to demonstrate OS improvement vs SUN (N = 323 vs 328; median 37.7 vs 34.3 months; HR 0.70 [95% CI 0.55–0.90]). PFS (median 16.6 vs 8.3 months; HR 0.56 [95% CI 0.46–0.68]) and ORR (55.7% [95% CI 50.1–61.2] vs 28.4% [95% CI 23.5–33.6]) benefits were maintained with N+C vs SUN, and 12.4% (N+C) vs 5.2% (SUN) of pts had a complete response. Median duration of response was 23.1 months with N+C vs 15.1 months with SUN. A higher percentage of pts experienced any reduction and ≥30% reduction from baseline with N+C vs SUN in target lesions at all organ sites assessed (Table). Among all treated pts, 97.2% (N+C; N = 320) vs 93.1% (SUN; N = 320) had a treatment-related adverse event (TRAE) of any grade (65.0% vs 54.1% had a grade ≥ 3 TRAE). Conclusions: N+C continued to provide survival improvement vs SUN among ITT pts in the final OS analysis, additionally PFS and ORR benefits with N+C were sustained with minimum 2-year follow-up. A higher proportion of pts experienced tumor shrinkage benefit with N+C vs SUN across all 4 organ sites assessed. No new safety signals emerged with extended follow-up in either arm. These results highlight N+C as a first-line treatment for pts with aRCC. Clinical trial information: NCT03141177. [Table: see text]

Abstract P5-16-15: Post-progression therapy outcomes in patients (pts) from the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC)

Abstract Background: SG is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. SG is FDA approved for pts with mTNBC who received ≥2 prior chemotherapies (≥1 in the metastatic setting). The confirmatory phase 3 ASCENT study (NCT02574455) in pts treated in second line or greater (2L+) mTNBC demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit of SG over single-agent chemotherapy treatment of physician’s choice (median PFS: 4.8 vs 1.7 months, HR 0.43, P<0.001; median OS: 11.8 vs 6.9 months, HR 0.51) in the full trial population, with a manageable safety profile. However, outcomes and patterns of subsequent therapy for pts who discontinue SG following progressive disease (PD) are not well characterized. This post hoc subgroup analysis investigates post-progression treatment and OS of pts who discontinued SG due to PD during the ASCENT trial. Methods: In ASCENT, pts with mTNBC refractory/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or progression. Post-progression outcomes were assessed in pts who discontinued SG due to progressive disease (PD). Pts were followed every 4 weeks for OS, including documentation of further therapy for breast cancer. Time to post-progression therapy was defined as the number of months from time of randomization until the initiation of subsequent anticancer therapy. OS was analyzed in pts who received post-progression therapy vs those who did not and defined as the number of months from randomization or from end of SG treatment, using Kaplan Meier estimates and Cox regression. Results: 222/267 (83%) pts who were randomized to receive SG discontinued SG due to PD. In these patients median age was 53 years (range, 27-82), median number of prior anticancer regimens was 4, and 7% had known germline BRCA1/2 mutations. Pts received SG for a median duration of 4.2 months (range, 0.0-18.7). Following SG discontinuation, post-progression therapy was received by 73% (n=163) of pts; common post-SG therapies included eribulin (n=70; 32%), carboplatin (n=34; 15%), capecitabine (n=34; 15%), and atezolizumab, (n=15; 7%). The median time to receipt of post-progression therapy was 5.4 months (range, 1.0-19.8). Median OS in pts who received any post PD treatment vs those who did not receive post PD treatment following SG was 13.4 vs 7.3 months (HR, 0.46; 95% CI, 0.32-0.67; P<0.0001) from time of randomization and 7.9 vs 2.0 months (HR, 0.14; 95% CI, 0.09-0.22; P<0.0001) from end of SG treatment, respectively. In pts who received eribulin, carboplatin, atezolizumab, or capecitabine, median OS was 14.1 (95% CI, 10.9-14.9), 13.6 (95% CI, 10.6-15.9), 16.5 (95% CI, 8.7 to not evaluable), and 14.9 (95% CI, 10.9-16.8) months from time of randomization and 8.4 (95% CI, 6.8-9.2), 8.9 (95% CI, 6.7-10.8), 8.6 (95% CI, 4.3 to not evaluable), and 8.9 (95% CI, 6.6-10.3) months from end of SG treatment, respectively. Conclusions: In ASCENT, the majority of pts who discontinued SG due to PD were able to receive subsequent therapy post-progression. Pts who received post PD therapy following SG had significantly improved median OS over those who did not receive further therapy. Pts who received eribulin, carboplatin, atezolizumab, or capecitabine, as post PD therapy had similar median OS. These results indicate that treatment with SG does not prevent receipt of further systemic therapy. Citation Format: Javier Cortés, Aditya Bardia, Delphine Loirat, Sara M. Tolaney, Kevin Punie, Mafalda Oliveira, Sara A. Hurvitz, Adam Brufsky, Sagar Sardesai, Kevin M Kalinsky, Tiffany Traina, Erika Hamilton, Joyce O’Shaughnessy, Véronique Diéras, Lisa A. Carey, Martine Piccart, Sibylle Loibl, Hope S. Rugo, Yanni Zhu, See Phan, Luca Gianni. Post-progression therapy outcomes in patients (pts) from the phase 3 ASCENT study of sacituzumab govitecan (SG) in metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-15.

Abstract P1-18-19: Long term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real world observational study (ESME)

Abstract Background The everolimus (EVE)-exemestane combination has been included in the International guidelines for metastatic HR+/HER2- breast cancer (mBC) since the results of the Bolero-2 trial. Marketing authorization has been granted in France in July 2012. A first report of the UNICANCER Epidemiological Strategy and Medical Economics (ESME) Research program described the real world use of everolimus therapy (ESMO 2017, #266). We report here updated data with long-term overall survival (OS) analyses, focusing on patients treated from 2012 onwards. Methods All patients (pts) who initiated treatment for a newly diagnosed mBC between 2008 and 2017 in all 18 French Comprehensive Cancer Centers have been included in the real life ESME database, which collects retrospective data using a clinical trial-like methodology. The primary endpoint of the present report was overall survival in pts who received everolimus. In order to adjust for differences between groups (EVE treated vs non EVE treated patients), we analyzed the impact of everolimus on OS and PFS by using a propensity score and inverse probability of treatment weighting (IPTW) sensitivity analyses, built with relevant cancer-related clinical variables in relation to survival and allocation of treatment. Those analyses were performed by line 1, 2 or 3 of treatment for mBC. Results The ESME program included 23,698 pts of whom 1897 with HR+/HER2- mBC received at least 1 dose of EVE and were diagnosed after 2012. Median age was 63 y (22-103). EVE pts were slightly younger than non-EVE pts (25.9% and 23.7% under 52 y, respectively, p=0.0574). EVE treated pts had more frequent non visceral metastases (52.3% vs 47.9%) and bone only metastases (38.5% vs 31.3%) at metastatic diagnosis, and less symptoms at mBC diagnosis (42.4% vs 47.5%) than non-EVE pts (all p values <.001). 94.3% of EVE pts had received an EVE-exemestane combination. EVE was administered either in the 1st, 2nd or 3rd line+ setting, in 3.3%, 14.7% and 25.3% of all cases respectively. At each line, treatments in the non-EVE treated pts included various endocrine therapy or chemotherapy regimen. Median follow-up was 47.9 m (0-98.7), and 61.4 m (2.1-98.7) for the overall- and EVE treated populations, respectively. Crude and landmark (6 and 12 months) OS analyses all suggested a longer OS with EVE based therapy. IPTW analyses by lines of treatment, comparing EVE-treated and non-EVE-treated patients, suggested a longer progression free survival with EVE when administered in the 3rd line setting (HR=0.82 CI95% [0.745-0.903], p<.0001). IPTW analyses consistently showed a significantly longer OS with EVE based treatment when administered in lines 1, 2 and 3 with respective HR values of 0.34, 0.34 and 0.23 (Table). Causes for EVE discontinuation were mainly disease progression (54%) and toxicity (26.6%). An exploratory analysis showed that 998 EVE treated patients (52.6%) also received a CDK4/6 inhibitor based treatment, mostly after EVE therapy (n=826, 82.8%). Median duration of CDK4/6 inhibitor therapy for those patients was 4.6 months (IQR 2.9-8.7). Conclusions These results are limited by the retrospective nature of the study and the lack of performance status, comorbidity or nutritional data. However, the long-term follow up of the ESME database suggests a favorable association between everolimus therapy and overall survival in HR+, HER2- mBC, persistent after IPTW adjusted analyses. HR (CI95%)p value12 months OS EVE vs not (unadjusted Kaplan Meier)Line 10.34 (0.16-072).005497% vs 93%Line 20.34 (0.22-0.52)<.000194% vs 85%Line 30.23 (0.14-0.36)<.000195% vs 79% Citation Format: Hélène Francois-Martin, Audrey Lardy-Cleaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule Augereau, Thomas Bachelot, Lionel Uwer, Marc Debled, Jean-Marc Ferrero, Corinne Veyret, Antony Goncalves, Michael Chevrot, Paul H Cottu. Long term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real world observational study (ESME) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-19.

Clinical outcomes associated with tislelizumab in patients (pts) with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (SOR) or lenvatinib (LEN) in RATIONALE-208.

420 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, demonstrated clinical activity and was well tolerated in pts with previously treated advanced HCC in the phase 2 RATIONALE-208 study (NCT03419897). At the time of this study, SOR and LEN were recommended first-line treatments for pts with advanced HCC and continue to have an important role in the first-line treatment of HCC despite the recent approval of new immuno-oncology-based combinations (atezolizumab and bevacizumab) in some regions. We report the clinical outcomes of pts with advanced HCC who were previously treated with SOR/LEN. Methods: Pts who had received ≥1 prior line of systemic therapy for advanced HCC received tislelizumab 200 mg intravenously once every three weeks. Objective response rate (ORR) by independent review committee (IRC) (ORRIRC), duration of response by IRC (DORIRC), progression-free survival by IRC (PFSIRC), overall survival (OS), and safety were evaluated in pts who had been previously treated with SOR/LEN. Results: As of February 2020, 249 pts were enrolled and 235 pts had received prior treatment with SOR/LEN, of whom 126 and 109 pts had received 1 or ≥ 2 prior lines of systemic therapy, respectively. At study entry, 211 (89.8%) pts had BCLC stage C and 187 (79.6%) pts had extrahepatic spread. Median follow-up duration for pts previously treated with SOR/LEN was 12.5 months and ORRIRC was 13.6% (95% CI: 9.5, 18.7), including 2 complete responses and 30 partial responses. Median DORIRC was not reached. Median PFSIRC and OS of pts previously treated with SOR/LEN was 2.7 months (95% CI: 1.6, 2.8) and 13.5 months (95% CI: 10.9, 15.8), respectively. Tislelizumab was generally well tolerated in pts previously treated with SOR/LEN (Table), and the most common treatment-emergent adverse events were increased aspartate aminotransferase (n=70; 28.1%) and alanine aminotransferase (n=52; 20.9%). Conclusions: Tislelizumab was investigated beyond the first-line setting, as effective second- and third-line treatment options are limited for pts with advanced HCC and there is an unmet medical need. This analysis indicates that tislelizumab is clinically active and well tolerated in pts with advanced HCC who have received prior systemic treatment with SOR/LEN. Clinical trial information: NCT03419897. [Table: see text]

Efficacy analysis of regorafenib combined with PD-1 inhibitors in elderly patients with metastatic colorectal cancer.

105 Background: Recently, an increasing number of patients (pts) with advanced colorectal cancer tend to receive regorafenib plus PD-1 inhibitors. However, there is a lack of information regarding real world effects of this therapeutic strategy, especially in elderly Chinese pts. We aimed to investigate the treatment patterns, clinical outcomes and prognostic factors of regorafenib plus PD-1 inhibitors therapy to Chinese elderly pts with advanced colorectal cancer. Methods: Retrospective analysis of a cohort of pts with advanced colorectal cancer received treatment of regorafenib combined with PD-1 inhibitors enrolled in our institution between January 2019 and January 2021. Among them, pts with 60 years or older were included in our final analysis. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan Meier curves, and other endpoints included objective response rate, prognostic factors. Results: At a median follow-up of 16.2 months, a total of 24 pts were enrolled in a real-world dataset from Henan Cancer Hospital. The median age was 68 years; 62.5% were female. The median OS and PFS were 15.03 months (95% CI 7.0-23.0) and 4.0 months (95% CI 1.8-6.2), respectively. 2/24 partial responses (PR) observed (ORR = 8.3%); Stable disease (SD) was obtained in 15/24. Disease control rate (PR plus SD) was therefore obtained in 17/24 (70.8%). When compared with PFS and OS in different initial daily doses group of regorafenib (such as ≤80, 120 or 160 mg), we concluded that there were no significantly difference between these groups. And similar results were found in final daily doses groups. However, it showed a trend toward better PFS in pts with ≥120 mg final daily doses group compared to <120 mg group (median PFS was 3.5 months in <120mg group versus 10.0 months in ≥120mg group). Median OS of pts for male gender demonstrated increasing trends compared with those female gender (20.2 months in males versus 13.2 months in females). Pts with previous treated with regorafenib had longer median OS than those without it (20.2 months versus 13.2 months). There were no obvious correlation for survival between pts only had liver metastasis and lung metastasis (P>0.05). No significant associations for survival could be seen in other tumor sites, K-RAS status, any kind of PD-1 inhibitors and whether previously treated with bevacizumab (P>0.05). Conclusions: This real-world dataset confirms that Chinese elderly pts with advanced colorectal cancer also can benefit from treatment of regorafenib combined with PD-1 inhibitors, similarly with this combination therapy strategies in all age pts. Furthermore, a longer survival time were obtained in pts with prior treated with regorafenib. The result also suggests that pts with ≥120mg final daily doses group had better PFS. However, further larger cohorts research should investigate whether the PFS advantage in high dose group could eventually lead to improved OS outcomes.

A phase Ⅱ, non-randomized, prospective trial of biweekly nab-paclitaxel in combination with ramucirumab for patients with previously treated advanced gastric or gastroesophageal junction cancer: B-RAX trial (JACCRO GC-09).

306 Background: The combination of paclitaxel (PTX) plus ramucirumab (RAM) has been the standard regimen for advanced gastric cancer (GC) or gastro-esophageal junction cancer (GJC) patients (pts) who were treated with fluoropyrimidine-containing regimen. In a phase 2 trial, it was showen that nab-PTX plus RAM has promising activity (objective response rate [ORR], 55 %; median progression free survival [PFS], 7.6 months) [Bando H, et al. Eur J Cancer 2018] and is, therefore, a treatment option. However, high incidence of myelosuppression led to discontinuation of the nab-PTX. Therefore, we conducted this study to investigate whether schedule modification to biweekly nab-PTX plus RAM therapy is safe and effective. Methods: Pts with GC or GJC treated with fluoropyrimidine-containing regimen were enrolled and received nab-PTX (100 mg/m2) on days 1, 8, and 15 and RAM (8 mg/kg) on days 1 and 15 of a 28-day cycle. The treatment schedule of pts with severe myelosuppression during the first cycle was modified to biweekly therapy from the second cycle. The primary endpoint was PFS in modified pts. Secondary endpoints included ORR, disease control rate (DCR), overall survival (OS), and safety. The exploratory analysis evaluated PFS and OS in pts who continued standard-schedule therapy. Based on the hypothesis that biweekly nab-PTX plus RAM therapy would improve PFS from 4.5 months to 7.0 months, 40 pts were required for a power of 0.8 with a one-sided α of 0.05. Results: Of the 81 pts who were enrolled, 76 pts received standard nab-PTX plus RAM in the first cycle and 47 pts (58%) were modified to the bi-weekly therapy. Pts characteristics in the modified pts were as follows: median age, 70 years; male, 72%; ECOG PS 0, 81%; and poorly differentiated adenocarcinoma or signet ring cell carcinoma, 45%. The median relative dose intensities of the entire period and after modification were 66% and 60%, respectively. In the modified pts, median PFS was 4.7 months (95% Confidence Interval [CI]: 3.7–5.6), median OS was 13.9 months (95% CI: 9.1–16.9), ORR was 25% (95% CI: 11–39), and DCR was 75% (95% CI: 61–89). Tumor shrinkage was observed in 61% of the pts (n = 36) with measurable lesion. In pts who could continue standard-schedule therapy, median PFS was 2.7 months (95% CI: 1.8–4.0) and median OS was 8.0 months (95% CI: 5.6–14.7). Severe (Grade >3) adverse events after modification were neutropenia (55%), anemia (13%), hypertension (17%), and peripheral sensory neuropathy (13%). Conclusions: Our study could not meet the primary endpoint for PFS. However, PFS in pts with standard-schedule therapy was numerically lower than that in the modified pts. The modification to biweekly schedule might be considered to be a treatment option for GC/GJC pts with severe myelosuppression in second-line nab-PTX plus RAM therapy. Clinical trial information: jRCTs031180061.

Nivolumab (NIVO) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy, safety, and subgroup analyses from CheckMate 649.

240 Background: CheckMate 649 is a randomized, global phase 3 study of 1L programmed death-1 (PD-1) inhibitor–based therapies in advanced non-HER2-positive GC/GEJC/EAC that demonstrated superior overall survival (OS) with NIVO + chemo vs chemo, leading to approvals in the US and other countries. Clinically meaningful long-term survival benefit with NIVO + chemo vs chemo was observed with 24 months (mo) of minimum follow-up in all randomized patients (pts) for both OS (HR 0.79 [95% CI 0.71–0.88]) and progression-free survival (PFS; HR 0.79 [95% CI 0.70–0.89]; Janjigian YY et al; ESMO 2021). We present expanded analyses of NIVO + chemo vs chemo with minimum follow-up of 24 mo. Methods: Adults with previously untreated, unresectable advanced or metastatic GC/GEJC/EAC were enrolled regardless of PD-ligand (L)1 expression. Pts with known HER2-positive status were excluded. Pts were randomized to NIVO (360 mg Q3W or 240 mg Q2W) + chemo (XELOX Q3W or FOLFOX Q2W), NIVO 1 mg/kg + IPI 3 mg/kg Q3W (4 doses, then NIVO 240 mg Q2W), or chemo. Dual primary endpoints were OS and PFS (per blinded independent central review) in pts with PD-L1 combined positive score (CPS) ≥ 5 for NIVO + chemo vs chemo. Hierarchically tested secondary endpoints included OS in NIVO + chemo vs chemo (PD-L1 CPS ≥ 1, then all randomized). Results: Of 2031 pts, 1581 were randomized to NIVO + chemo or chemo. In all randomized pts, 41% of pts (NIVO + chemo) and 44% of pts (chemo) received subsequent therapy. Median PFS2 (time from randomization to progression after subsequent systemic therapy, initiation of second subsequent systemic therapy, or death, whichever is earlier) was 12.2 (95% CI 11.3–13.5) mo with NIVO + chemo and 10.4 (95% CI 9.7–11.2) mo with chemo (HR 0.75 [95% CI 0.67–0.84]). 51% of pts (NIVO + chemo) and 43% of pts (chemo) had > 50% reduction from baseline in tumor burden, while 24% and 17% had > 80% reduction, respectively. The HR (95% CI) for OS was 0.66 (0.56–0.77) among pts with a PD-L1 CPS ≥ 10 (median OS for NIVO + chemo vs chemo: 15.0 [95% CI 13.7–16.7] vs 10.9 [95% CI 9.8–11.9] mo). OS benefit was observed with NIVO + chemo vs chemo across multiple additional subgroups, and these data will be presented. No new safety signals were identified. The majority of the treatment-related adverse events with potential immunologic etiology were grade 1 or 2 and grade 3 or 4 events were reported in ≤ 5% of pts in both treatment arms. Conclusions: NIVO + chemo continued to demonstrate clinically meaningful efficacy and an acceptable safety profile with longer follow-up, further supporting the use of NIVO + chemo as a standard 1L therapy in previously untreated pts with advanced GC/GEJC/EAC. Clinical trial information: NCT02872116.

117TiP A phase II study of toripalimab combined with paclitaxel/carboplatin for the first-line treatment of advanced thymic carcinoma

117TiP A phase II study of toripalimab combined with paclitaxel/carboplatin for the first-line treatment of advanced thymic carcinoma

68P A phase Ib study of lenvatinib + pembrolizumab (LEN + PEMBRO) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 116 follow-up analysis

68P A phase Ib study of lenvatinib + pembrolizumab (LEN + PEMBRO) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 116 follow-up analysis

63P Shifting treatment landscape and overall survival (OS) by PD-L1 expression level among patients (pts) with advanced non-small cell lung cancer (aNSCLC)

Since 2016, when the FDA approved the first immune checkpoint inhibitor (ICI) for first-line (1L) treatment of pts with aNSCLC with ≥50% PD-L1 expression, some ICI indications have been expanded to include pts with PD-L1 ≥1% or regardless of expression level. Current NCCN guidelines reflect these changes. This study describes real-world (RW) 1L ICI treatment trends and OS of pts with aNSCLC across PD-L1 expression levels.

Normal Life Expectancy for Polycythemia Vera Patients Is Possible

▪Introduction: Polycythemia vera (PV), a chronic myeloproliferative neoplasm, is characterized by shortened overall survival (OS) due to potentially fatal thrombosis, progression to myelofibrosis (MF), and acute leukemia. Treatment with aspirin, attentive phlebotomy (PHL) and cytoreductive agents can prevent thrombosis; but it is unknown whether available treatments can achieve a normal life-span for PV patients (pts). Our objective was to assess the extent by which PV alters OS of pts receiving available treatment at our center and in the community.Methods: We obtained demographics and survival data of adult PV pts from our Weill Cornell Medicine (WCM) Research Database Repository (PV-WCM) diagnosed from 1974-2020 as previously described (Abu-Zeinah et al. Leukemia 2021); and from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) Program, 2001-2017. PV-WCM thrombosis and MF progression data were available. WCM institutional review board approval and SEER data use agreement were in place. OS of PV pts was estimated using Kaplan-Meier (KM) analysis. Propensity Score Matching was used to identify a subgroup of SEER pts (PV-SEER) with similar age, sex, and race demographics to PV-WCM for comparison of OS. Cox proportional hazards was used for multivariable analysis (MVA) of survival. Actuarial survival of the US population matched by age, sex, race, and year-of-birth was obtained from US Census. Observed OS was compared to actuarial OS using one-sided log-rank test.Results: We identified 470 PV-WCM and 16,492 PV pts from SEER. The median OS of the PV-WCM cohort and the SEER population was 26.6 and 12.8 years, respectively, but the groups differed by age and sex (Fig 1A). PV-WCM and matched PV-SEER, however, were well balanced by age, sex, and race (standardized mean difference <0.1). The median OS of PV-WCM was 10.8 years longer than PV-SEER (p<0.001, Fig 1B). MVA confirmed 65% lower mortality in the PV-WCM group relative to the PV-SEER population (p<0.001, Fig 1C). PV-SEER OS was shorter than actuarial OS of the US population (mortality HR 2.47, p<0.001), whereas PV-WCM OS was not significantly different than expected (mortality HR 1.15, p=0.136). Excess late mortality was observed in PV-WCM after 17 years, potentially due to increased incidence of MF progression, affecting almost 50% of PV pts after 25 years (Fig 1D).Discussion: These data point to the success of attentive management with aspirin, targeted PHL, and cytoreductive therapy at a specialty center in reducing the mortality of PV, owing in part, to ELN and NCCN treatment recommendations for preventing fatal thrombosis. Although excess thrombosis was not eliminated in PV-WCM pts, the incidence rate was low after the first two years (Fig 1D). In contrast, the incidence of MF progression increased, potentially contributing to excess late mortality. Current PV risk stratification and treatment recommendations neither predict nor aim to mitigate progression to MF, and do not satisfy the needs of younger, low-risk pts who are often symptomatic and harbor a lifetime threat of progression (Fig 1E). The recent Low-PV study showed that low-risk pts may also benefit from cytoreductive therapy with an agent such as interferon-alpha (rIFNα) over PHL alone (Barbui et al. Lancet Hematol 2021). PV-WCM pts treated with rIFNα (n=137), previously shown to have improved MF-free survival and OS (Abu-Zeinah et al. Leukemia 2021), had an OS similar to the matched US population (p=0.33, Fig 1F); whereas pts not treated with rIFNα had modestly shortened OS (HR 1.26, p=0.03). Because PV progression is among the leading causes of late morbidity and mortality, and available therapy can mitigate this, it may be time to reconsider and improve upon PV risk stratification and treatment.Conclusion: This large population-based and single center study shows that although PV survival remains shortened, normal life expectancy for PV pts is possible with available care. The discrepancy between survival in the community and at a specialized center highlights the need for greater community outreach, health equity, and education regarding treatment standards for PV. Hopefully, this study motivates development of new PV risk stratification and treatment recommendations that focus not only on hematologic control and thrombosis prevention, but also on preventing MF progression, improving OS, and restoring normal life expectancy. [Display omitted] DisclosuresAbu-Zeinah: PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. Silver: Abbvie: Consultancy; PharamEssentia: Consultancy, Speakers Bureau. Scandura: CR&T (Foudation): Research Funding; European Leukemia net: Honoraria, Other: travel fees ; MPN-RF (Foundation): Research Funding; Constellation: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure:Interferon-alpha is used off label in the treatment of polycythemia vera.