Characteristics Of Long-term Survivors Research Articles

Characteristics of long-term survivors with malignant pleural mesothelioma

Pleural mesothelioma (PM) is a cancer with usually a dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centres around the world. This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥ 5 years from surgery) treated within a multimodality therapy approach including macroscopic complete resection. Overall survival was calculated with Kaplan Meier analysis and cases were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis. There were 276 long-term survivors, most were male (n=166, 63%) with a median age of 59 (range 21-83) years at time of diagnosis. The histology for 246 was epithelioid and non-epithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients were dead, 104 were alive and 10 were lost to follow-up. Pathological tumor stages were: pT1 (n=50), pT2 (n=63), pT3 (n=90) or pT4 (n=16), pN0 (n=150), pN1 (n=20) and pN2 (n=39). The matched control dataset included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, there was moderate evidence that a low white blood cell (WBC) count before surgery was more often observed in long-term survivors. The data show that long-term survival in PM is possible in a subgroup of surgically treated patients; histological subtype and WBC count seem to be prognosticators for longer survival.

Characteristics of long-term survivors with EGFR mutant (EGFRm) metastatic non-small cell lung cancer (mNSCLC).

9116 Background: Although osimertinib has become standard first-line (1L) therapy for patients (pts) with EGFRm mNSCLC, a subset treated with earlier-generation EGFR-targeted TKIs and chemotherapy have had long-term survival. We sought to characterize clinical features of long-term survival in pts with EGFRm mNSCLC treated prior to the osimertinib era. Methods: Data were abstracted from electronic medical records at 12 cancer centers participating in the Academic Thoracic Oncology Medical Investigator’s Consortium (ATOMIC). We included patients with mNSCLC with sensitizing mutations in EGFR who started 1L systemic therapy before 2015. Survival distributions and predictors were assessed using Kaplan-Meier estimates and a multivariable Cox proportional hazards model including time-dependent brain metastasis (met) development, age, 1L therapy (targeted vs. chemotherapy), sex, race, and smoking status. Multivariable logistic regression was used to evaluate baseline predictors associated with 5+ year survival vs. not for those with known survival status at 5 years after start of 1L. Results: We identified 304 patients (69% female, 56% White, 29% Asian, mean age 61.2). First-line targeted therapy was given in 70% of patients. With a median follow-up of 81.5 months, median overall survival was 63.5 months (95% CI 59.4-71.9). 135 (44%) pts survived 5+ years; among those with baseline next-generation sequencing (NGS), presence of a baseline pathogenic ERBB2 variant was higher in 5+ year survivors (4/51 [8%], 2x amplification, y772_A775dup, S310F) v others (1/65 [2%], amplification). Among 161 pts with baseline brain imaging, both baseline and on-treatment development of brain mets were associated with worse survival (HR 1.29, 95% CI 1.21-1.37; HR 1.59, 95% CI 1.47-1.72; both P &lt; 0.001). Excluding 22 patients lost to follow-up before 5 years, a history of smoking (OR 2.99, 95% CI 1.35-6.90, P = 0.008) and baseline brain metastases (OR 3.57, 95% CI 1.64-8.13, P = 0.002) were associated with death before 5 years. Conclusions: Long-term survivors with EGFRm mNSCLC treated before the osimertinib era were more likely to be nonsmokers and have no baseline brain metastases. This highlights a subset of EGFRm patients who had excellent outcomes with older treatment strategies and may not benefit as much from intensification approaches. Additional baseline mutational data will be presented at the conference.

141O Durvalumab (D) ± tremelimumab (T) + platinum-etoposide (EP) in 1L extensive-stage (ES) SCLC: Characteristics of long-term survivors in the CASPIAN study

In the phase 3 CASPIAN trial, 1L D+EP significantly improved OS vs EP and OS benefit was sustained after >3 years median follow-up (HR 0.71; 95% CI 0.60‒0.86; nominal p=0.0003). Here we assess clinical and molecular characteristics of pts who experienced long-term survival in CASPIAN. 805 pts with ES-SCLC were randomised 1:1:1 to D+EP, D+T+EP or EP. In post-hoc analyses, clinical characteristics were assessed in long-term survivors (LTS; n=94), defined as pts still alive at the 22 Mar 2021 data cutoff (DCO; median follow-up 39.4 mo). PD-L1 expression and tissue tumour mutational burden (tTMB) were assessed in the biomarker evaluable populations (BEPs) according to OS landmark (18 and 36 mo). There were 44 (16%), 37 (14%) and 13 (5%) LTS in the D+EP, D+T+EP and EP arms, respectively. LTS had slightly higher incidence of some favourable prognostic factors at baseline; incidence of brain/liver mets was lower among LTS vs ITT, although they still occurred in some LTS (Table). More LTS received ≥4 cycles EP than ITT, with a higher median overall treatment exposure in the IO+EP arms. 46 (27 D+EP; 19 D+T+EP) LTS were ongoing D treatment at this DCO. ORR and 24-mo PFS rates were higher for LTS vs ITT in the IO+EP arms. Rates of serious AEs (SAEs) were similar in LTS and ITT (Table). In the D+T+EP arm only, incidence of PD-L1 expression on ≥1% of tumour cells (TC) or immune cells (IC) (but not tTMB >10 mut/Mb) was enriched in pts with OS ≥18 mo vs OS <18 mo (Table); enrichment was maintained with OS ≥36 mo (data will be presented). There were >3 times as many LTS in the D+EP arm vs the EP arm. LTS were more likely to have favourable prognostic characteristics than ITT, although some LTS had brain/liver mets at baseline. Notably, most LTS completed EP induction and, in both the IO+EP arms, had substantially greater overall treatment exposure, as well as achieving higher ORR and longer PFS, vs ITT. There was no evidence of cumulative toxicity based on SAEs.Table: 141OD+EPD+T+EPEPLTSITTLTSITTLTSITTn442683726813269Median age, yrs59.56259636363Male, %507170755468PS 0, %433746413133Brain mets, %710814010Liver mets, %204030441539Median overall exposure, wks15928160232019D dose delays, %75577659‒‒≥4 cycles EP, %*1008792819285Unconfirmed ORR, %†89799274697124-mo PFS, %†65116712553SAEs, %343254473136BEP, n/N (%)OS ≥18 moOS <18 moOS ≥18 moOS <18 moOS ≥18 moOS <18 moPD-L1 (TC or IC) ≥1%13/46 (28)25/106 (24)24/47 (51)30/110 (27)7/24 (29)25/103 (24)tTMB >10 mut/Mb16/29 (55)41/78 (53)16/30 (53)32/75 (43)4/16 (25)22/55 (40)*Based on etoposide†From 27 Jan 2020 DCO; RECIST data not collected after this DCO Open table in a new tab

Molecular characterization of long-term survivors of hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most fatal cancers, and the majority of patients die within three years. However, a small proportion of patients overcome this fatal disease and survive for more than five years. To determine the molecular characteristics of long-term survivors (survival ≥ 5 years), we analyzed the genomic and clinical data of hepatocellular carcinoma patients from The Cancer Genome Atlas and the International Cancer Genome Consortium databases, and identified molecular features that were strongly associated with the patients’ prognosis. Genes involved in the cell cycle were expressed at lower levels in tumor tissues from long-term survivors than those from short-term survivors (survival ≤ 1 years). High levels of positive regulators of the G1/S cell cycle transition (cyclin-dependent kinase 2 [CDK2], CDK4, Cyclin E2 [CCNE2], E2F1, E2F2) were potential markers of poor prognosis. Hepatocellular carcinoma patients with TP53 mutations were mainly belonged to the short-term survivor group. Abemaciclib, an FDA-approved selective inhibitor of CDK4/6, inhibited the cell proliferation and tumor growth of hepatocellular carcinoma cells in vitro and in vivo. Thus, high G1/S transition-related gene levels and TP53 mutations are promising diagnostic biomarkers for short-term survivals, and abemaciclib may be a potential targeted drug for hepatocellular carcinoma.

Impact of clinical factors and surgical outcome on long-term survival in high-grade serous ovarian cancer: a multicenter analysis

IntroductionLong-term survivors of ovarian cancer are a unique group of patients in whom prognostic factors for long-term survival have been poorly described. Such factors may provide information for a more...

Metastatic pancreatic cancer: Characteristics of long-term survivors

Metastatic pancreatic cancer: Characteristics of long-term survivors

1664-P: Does “Healthy Diabetes” Exist? Long-Term Survival in Diabetes Heart Study Participants

The Diabetes Heart Study, initiated in 1997, includes examination and follow-up of 1221 European Americans, 85% with type 2 diabetes (T2D). Baseline examination included extensive medical history, laboratory measures, and CT-imaging for coronary artery calcium (CAC). Through 2016, 451 participants had died. CVD-attributable deaths occurred over an age range of 39-93 years. In high-risk participants with T2D and CAC&amp;gt;1000, 52% died after mean 14.9 year follow-up; however, many are still alive. 64% of surviving T2D participants lived with diabetes for &amp;gt;20 years and 16.4% (31 male, 46 female) &amp;gt;30 years. Among deceased individuals, the average duration of diabetes was 20.8 years. Comparing long-term T2D-survivors to deceased, difference in CAC, a powerful predictor of mortality, was not significant (P=0.85) with mean CAC in survivors (male=4730, female=1147) and deceased (male=4085, female=1220). Conventional clinical measures did not differ significantly (glucose, HbA1c, BP; P&amp;gt;0.05) or were modestly different (cholesterol P=0.033; LDL P=0.035). There was a difference in the use of statins at baseline: 53% in survivors, 41% in deceased (P=0.05) and C-reactive protein (P=0.04). The strongest individual trait difference was in duration of T2D at baseline (P&amp;lt;0.0001) but mean T2D-duration at baseline in survivors was 20 vs. 12.5 years in deceased). Thus, a significant number of individuals with T2D have long-term survival even in the presence of a significant burden of subclinical CVD, but conventional clinical measures provide little Insight. Research into the characteristics of long-term survivors with T2D may prove beneficial to all T2D patients. Disclosure D.W. Bowden: None. J. Xu: None. B.I. Freedman: Consultant; Self; AstraZeneca, Ionis Pharmaceuticals, Inc. N. Palmer: None. F. Hsu: None. Funding National Institutes of Health

Abstract P1-08-15: Characteristics of long-term survivors with metastatic breast cancer

Abstract Background: Survival with metastatic breast cancer (MBC) is highly variable and only ˜16% survive 10 years from the primary cancer diagnosis. In addition to treatments, proposed contributors to increased survival include cancer subtype, distribution of metastases, diet, exercise, and use of complementary and alternative medicine (CAM). We aimed to characterize long-term survivors with MBC through a self-administered survey. Methods: Patient advocates and researchers collaborated on developing and administering an ongoing web-based questionnaire (outliers.cancer.wisc.edu). Participants were recruited to this IRB-approved project through fliers, social media, MBC conferences, and Susan Love's Army of Women, with a recruiting focus on long-term survivors. Women and men are eligible if they are age ≥18 years old and have MBC by self-report. Eligible participants were invited to complete a detailed 28-part survey in English. Preliminary analysis was conducted by descriptive comparison of survivors ≥ 10 years from primary diagnosis versus those &amp;lt; 10 years. Results: Between March 6 and June 17, 2018, a total of 475 women and 1 man self-reported as living with MBC consented and completed the survey. Participants represented 48 U.S. states (n=414), and other countries on 4 continents (n=54). Two thirds of respondents (315) reported using medical records in preparing responses. Age of respondents ranged from 32-83 years (median 55), and participants survived from 4 months to 50 years (median 8.7), from primary breast cancer diagnosis. A total of 206 had lived ≥10 y from primary diagnosis and 270 &amp;lt;10 y (Table). Characteristics of long-term survivors and non-long term survivors with MBC Survival from primary diagnosis Survival from primary diagnosisFactor≥10 y&amp;lt;10 yFactor≥10 y&amp;lt;10 yAge, mean6052Bone metastasis only*36%40%Stage 411%47%BMI, mean27.428.5HR+HER2-66%65%Alcohol &amp;gt;2 drinks/wk26%20%HR-HER2+6%9%Smoking history36%33%HR+HER2+24%22%Sedentary23%21%Triple negative4%4%CAM use20%20%Oligometastatic (1-3)*53%50%Sleep hours/d, mean7.77.6*Number/site of tumors at time of metastatic presentation As expected, longer-term survivors were older and were less likely to have been diagnosed at stage 4. Surprisingly, there were no major differences in prevalence of breast cancer subtypes, though triple-negative breast cancer was rare in both groups. Long-term survivors reported modestly more alcohol intake and lower BMI. The two groups were well matched for oligometastatic and bone-only disease, which have been previously associated with longer survival. Additionally, there were similar rates of prior smoking, CAM use, and sedentary behavior. Conclusion: Interim analysis of this ongoing survey of MBC survivors finds that many disease and behavioral characteristics are similar between long-term versus short term survivors. Additional factors such as treatments, diet, and supplements will reported. Other possible factors, including tumor genetics, treatments and immunologic factors will be evaluated separately. Citation Format: Burkard ME, Lemmon K, Gilbert AD, Zhang X, Trentham-Dietz A, Dahl E, Rocque G. Characteristics of long-term survivors with metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-08-15.

Characteristics of long-term survivors in stage III gastric cancer patients.

163 Background: Stage III gastric cancer patients had poor prognosis. This study aims to evaluate prognostic factor of stage III gastric cancer. Methods: We retrospectively studied 126 patients who were treated for stage III gastric cancer from Jan. 2007 to Dec. 2010 at Korea University Hospital and performed complete follow up for five years. Long-term survivor was defined more than five years survivor after gastrectomy. Results: Long-term survivor was 70 patients (55.6%). Tumor size, lymph node involvement, lymphatic invasion, venous invasion and neural invasion had prognostic significance on univariate analysis. But location of tumor, gross type, depth of invasion, TNM stage, combine resection, complication, histologic differentiation, type of operation and adjuvant treatment had no prognostic significance. The most common recurrence pattern was peritoneal recurrence (57.4%) according to analysis of recurrence pattern. The disease free survival according recurrence pattern was peritoneal recurrence (21.3 months), hematogenous recurrence (32.1 months), distant lymph node recurrence (12.0 months) and locoregional (12 months). The disease specific survival according recurrence pattern was peritoneal recurrence (9.2 months), hematogenous recurrence (11.3 months), distant lymph node recurrence (16.2 months) and locoregional (26.9 months). Conclusions: Lymph node involvement were the most significant prognostic factors on stage III gastric cancer after curative resection. Therefore, postoperative surveillance and adjuvant therapy were very carefully selected in stage III gastric cancer patient with extensive lymph node metastasis.

NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors

BackgroundLiposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) is approved for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This approval was based on significantly improved median overall survival compared with 5-FU/LV alone (6.1 vs 4.2 months; hazard ratio [HR], 0.67) in the global phase 3 NAPOLI-1 trial. Here, we report the final survival analysis and baseline characteristics associated with long-term survivors (survival of ≥1 year) in the NAPOLI-1 trial. Patients and methodsPatients with mPDAC were randomised to receive nal-IRI + 5-FU/LV (n = 117), nal-IRI (n = 151), or 5-FU/LV (n = 149) for the first 4 weeks of 6-week cycles. Baseline characteristics and efficacy in the overall population were compared with those in patients who survived ≥1 year. Through 16th November 2015, 382 overall survival events had occurred. ResultsThe overall survival advantage for nal-IRI+5-FU/LV vs 5-FU/LV was maintained from the original nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1) analysis (6.2 vs 4.2 months, respectively; HR, 0.75; 95% confidence interval: 0.57–0.99). Median progression-free survival, objective response rate and disease control rate also favoured nal-IRI+5-FU/LV therapy. Estimated one-year overall survival rates were 26% with nal-IRI+5-FU/LV and 16% with 5-FU/LV. Baseline characteristics associated with long-term survival in the nal-IRI+5-FU/LV arm were Karnofsky performance status ≥90, age ≤65 years, lower CA19-9 levels, neutrophil-to-lymphocyte ratio ≤5 and no liver metastases. No new safety concerns were detected. ConclusionsThe survival benefits of nal-IRI+5-FU/LV versus 5-FU/LV were maintained over an extended follow-up, and prognostic markers of survival ≥1 year were identified. Clinical trial registration numberNCT01494506.

Abstract 598: Utility of cell therapy to control relapsed acute myeloid leukemia following allogeneic stem cell transplantation: Does cell source matter

Abstract Introduction: Although allogenic hematopoietic stem cell transplantation (Allo-SCT) is curative therapy for acute myeloid leukemia (AML), many patients experience relapse following allo-SCT. For these patients, it is well known that donor lymphocyte infusion (DLI) could rescue a certain proportion via graft versus leukemia effect. On the other hand, with the advance of abundant stem cell harvesting techniques, residual stem cell after allo-SCT is also frequently used as a rescue therapy for AML relapse. However, clinical utility of residual stem cell is not well established yet. Hence, in this study, we compare the outcome of DLI with residual stem cell infusion in relapsed AML after allo-SCT. Materials and Methods: We retrospectively reviewed the AML patients who underwent DLI or residual stem cell infusion for relapsed disease after allo-SCT from 2001 to 2017 in Seoul National University Hospital. We analyzed factors including overall survival (OS), cell counts, disease status at cell therapy, and GVHD development. Our primary outcome was to compare OS after cell therapy between DLI group and residual stem cell group. Results: A total of 81 patients were analyzed. There were 50 patients (25 males and 25 females) who received cell therapy using DLI, and 31 patients (11 males and 20 females) who received residual stem cell infusion. There was no difference in age and duration from allo-SCT to cell therapy between the two groups. Majority of patients received cell therapy for first relapse after allo-SCT (63% in DLI, 93% in residual stem cell group). Median CD3 cell count infused was not different between DLI and residual stem cell product (median value of 0.967 X 108/kg and 0.964 X 108/kg). Median CD34 cell dose was 2.34 X 106/kg in residual stem cell group. There was no difference in OS between the two groups (median OS 8.5 months for DLI and 10.2 months for residual stem cell group, p-value 0.673). GVHD occurred in 44% in DLI group and 41.9% in residual stem cell group. When multivariate analysis was performed, disease status at stem cell therapy or duration from allo-SCT to relapse did not show any significant difference. Characteristics of long-term survivors after cell therapy following relapse after allo-SCT could be summarized as whether to acquire bone marrow CR after therapy. Conclusion: This study demonstrates that clinical utility of DLI and residual stem cell infusion is similar in relapsed AML after allo-SCT. Hence, residual stem cell could be used as an alternative source for T-cell therapy following allo-SCT. Citation Format: Woochan Park, Inho Kim, Sung-soo Yoon, Seonyang Park, Youngil Koh. Utility of cell therapy to control relapsed acute myeloid leukemia following allogeneic stem cell transplantation: Does cell source matter [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 598.

Characteristics of long-term survivors and early-recurrence patients after curative resection of pancreatic ductal adenocarcinoma - a clinico-pathological analysis

Characteristics of long-term survivors and early-recurrence patients after curative resection of pancreatic ductal adenocarcinoma - a clinico-pathological analysis

Clinical and Pathologic Characteristics of Long-Term Survivors of Type 2 Endometrial Cancer

Clinical and Pathologic Characteristics of Long-Term Survivors of Type 2 Endometrial Cancer

Nivolumab (N) plus ipilimumab (I) as first-line (1L) treatment for advanced (adv) NSCLC: 2-yr OS and long-term outcomes from CheckMate 012.

9093 Background: The fully human anti–PD-1 antibody N offers long-term OS benefit in patients (pts) with previously treated adv NSCLC. Adding I (anti–CTLA-4 antibody) to N has been shown to improve clinical activity vs either agent alone in multiple tumor types. We present long-term data for 1L N+I treatment of pts with adv NSCLC from CheckMate 012. Methods: In two cohorts in this phase 1 study, pts with recurrent stage IIIb/IV, chemotherapy-naive NSCLC and ECOG PS 0–1 received N 3 mg/kg Q2W combined with I 1 mg/kg Q12W (n=38) or Q6W (n=39) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was safety and tolerability. Secondary endpoints included investigator-assessed ORR (RECIST v1.1) and PFS. Exploratory endpoints included OS and efficacy by tumor PD-L1 expression. Results: In the N+I Q12W and N+I Q6W cohorts, respectively, 42% and 31% of pts experienced grade 3–4 treatment-related (TR) AEs; 18% in each cohort discontinued due to any-grade TRAEs. The most frequently reported any-grade TRAEs were pruritus (26%) and diarrhea (21%) with N+I Q12W, and fatigue (26%) and diarrhea (23%) with N+I Q6W. There were no TR deaths. N+I showed promising efficacy (table). While efficacy was enhanced with increasing PD-L1 expression, activity was noted in pts with &lt;1% PD-L1 (table). Of 6 complete responses (CRs), 3 were in pts with &lt;1% PD-L1. Conclusions: 1L therapy with N+I demonstrates a manageable safety profile and promising, durable efficacy (including pathological CRs) in adv NSCLC; efficacy was enhanced in pts with ≥1% PD-L1 tumor expression. Longer follow-up data, including 2-yr OS and characteristics of long-term survivors, will be presented. Clinical trial information: NCT01454102. [Table: see text]

Characteristics of long-term survivors in a randomized phase III trial (NAPOLI-1) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan (nal-IRI; MM-398) + 5-FU/LV.

293 Background: nal-IRI, a liposomal formulation of irinotecan, plus 5-FU/LV is approved in the United States and Taiwan for patients (pts) with mPDAC previously treated with gemcitabine-based therapy. Primary analysis of the NAPOLI-1 trial (NCT01494506) showed that nal-IRI+5-FU/LV significantly improved median overall survival vs 5-FU/LV (6.1 vs 4.2 months; HR, 0.67; 95% CI, 0.49-0.92; P = 0.012; Wang-Gillam et al, Lancet. 2016). Herein we report baseline characteristics of pts surviving ≥1 year (data cutoff, Nov 2015). Methods: This analysis includes 117 pts assigned to treatment with nal-IRI 70 mg/m2 (free base) + 5-FU/LV 2400/400 mg/m2 q2w, and 119 pts assigned to treatment with 5-FU/LV 2000/200 mg/m2weekly for weeks 1-4 q6w. Results: A total of 29 (25%) pts in the nal-IRI+5-FU/LV arm and 17 (14%) in the 5-FU/LV arm survived ≥1 year. These pts typically had better performance status, lower CA19-9 (U/mL) levels, and were less likely to have liver metastases at baseline, compared with the overall population (Table). For long-term survivors in the nal-IRI+5-FU/LV arm, a higher proportion of pts had neutrophil-to-lymphocyte ratio (NLR) &gt;5, a marker of poor prognosis, suggesting that higher NLR may potentially be predictive of survival outcome with nal-IRI+5-FU/LV. Conclusions: More pts receiving nal-IRI+5-FU/LV versus 5-FU/LV were alive beyond 1 year. The most prominent prognostic markers of survival ≥1 year included lower CA19-9, KPS ≥90 and absence of liver metastases. These analyses may be limited by small sample sizes. Clinical trial information: NCT01494506. [Table: see text]

P1.01-040 Long-Term Survival in Metastatic Non-Small-Cell Lung Cancer: An Investigation Using Surveillance, Epidemiology and End Results Data

The introduction of new effective modalities for the treatment of metastatic non-small cell lung cancer (NSCLC), such as targeted therapies and immunotherapy, has resulted in reports of long-term survival in small sub-groups of patients treated with these therapies. It is therefore important to understand the frequency and characteristics of long-term survivors in large cohorts of advanced-stage lung cancer patients who were diagnosed and treated prior to the advent of these new therapies. A survival analysis of data from the Surveillance Epidemiology and End Results database was performed. The cohort was limited to patients diagnosed with stage IV NSCLC, squamous and adenocarcinoma histology only, between 1991 and 2007, with follow-up through 2012. Outcomes and factors associated with extended survival were evaluated in the 10% of patients with longest survival (long-term survivors, ≥21 months) vs. 90% short-survival patients (< 21 months). Patients surviving ≥ 5 years were compared with those surviving <5 years and ≥21 months. Demographic, tumor characteristic, and treatment differences between long-term and short-survival patients were compared using chi-square and Student’s T-test for categorical and continuous variables, respectively. For descriptive analyses unadjusted for confounders, Kaplan Meier curves and log-rank tests were used to compare survival by histology and long-term survival status. Among the 44,387 patients diagnosed at stage IV, long-term survivors (4,544) are distinguishable from short-survival patients (39,843) by younger age, female sex, Asian/ Pacific Islander race, lower tumor grade, adenocarcinoma histology, upper lobe site, and treatment with surgery. Among only long-term survivors (≥ 21 months), predictors of longest survival are younger age, lower tumor grade, and treatment by surgery and radiation. Median survival increased over time from 3 to 4 months for short-survival patients versus 30 to 36 months for long-term survivors. Notably, 1.5% of patients survived >5 years even prior to modern combination chemotherapy regimens, targeted therapies, and immunotherapy. Despite the poor overall survival of patients diagnosed with stage IV NSCLC, the top 10% of survivors have significantly longer survival than the rest and a sub-population of individuals with extraordinary survival is identifiable. The discrepancy in median survival between long-term survivors and the rest suggests that long-term survivors comprise a disproportionate percentage of clinical trial participants and provides a rationale for more detailed clinical and molecular analyses in order to improve therapeutic targeting and future study design.

Characteristics of long-term survivors in a diabetic dialysis patient collective (4D study)

Characteristics of long-term survivors in a diabetic dialysis patient collective (4D study)

Abstract CT001: Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial

Abstract Background: In previously treated MEL patients (pts), the results of an early phase I trial with NIVO monotherapy (CA209-003) demonstrated tumor responses that were durable even after treatment discontinuation (Topalian et al. J Clin Oncol 2014;32:1020). We report extended follow-up with 5-year overall survival (OS) data from this study. Methods: IPI-naïve pts (N = 107) who had received 1-5 prior systemic therapies for MEL were treated with NIVO (0.1, 0.3, 1, 3, or 10 mg/kg) every 2 weeks for ?96 weeks. Pts were followed for OS, progression-free survival (PFS), long-term safety, and response duration after discontinuing NIVO treatment. Pts began treatment in October 2008, and current data were analyzed in October 2015 with a minimum follow-up of 45 months (time from when the last pt received his or her first dose of NIVO). Results: Median age of the pts was 61 years, 67% were male, 97% had an ECOG performance status of 0 or 1, 62% had received ?2 prior systemic therapies, and 36% had elevated lactate dehydrogenase levels at baseline. In all 107 pts, the 60-month OS rate was 34% (95% confidence interval [CI]: 25-43) and median OS was 17.3 months (95% CI: 12.5-37.8) (Table). OS rates appeared to plateau at ∼48 months, although further follow-up is needed. Similar results were observed with NIVO at 3 mg/kg, the currently approved monotherapy dose (Table). At the last timepoint for tumor assessment, PFS rates at 30 months were 18.6% and 25.7% for all pts and those who received NIVO at 3 mg/kg, respectively. Conclusions: This analysis represents the longest survival follow-up of pts who received anti-PD-1 therapy in a clinical study. In this heavily pretreated population of MEL pts, these results suggest durable, long-term survival following NIVO monotherapy, with 34% of pts alive at 5 years. Characteristics of long-term survivors and updated safety data will also be presented. OS ratesNIVO 3 mg/kg (n=17)All Patients (N=107)OS rate, % (95% CI)*12-month64.7 (37.7-82.3)62.7 (52.6-71.2)24-month47.1 (23.0-68.0)48.0 (38.1-57.2)36-month41.2 (18.6-62.6)42.1 (32.4-51.4)48-month35.3 (14.5-57.0)34.8 (25.7-44.1)60-month35.3 (14.5-57.0)33.6 (24.6-42.9)Median OS, months (95% CI)20.3 (7.2-NR)17.3 (12.5-37.8)*Based on Kaplan-Meier estimates.NR, not reached. Citation Format: F. Stephen Hodi, Harriet Kluger, Mario Sznol, Richard Carvajal, Donald Lawrence, Michael Atkins, John Powderly, William Sharfman, Igor Puzanov, David Smith, Philip Leming, Evan Lipson, Janis Taube, Robert Anders, Christine Horak, Joel Jiang, David McDermott, Jeffrey Sosman, Julie Brahmer, Drew Pardoll, Suzanne Topalian. Durable, long-term survival in previously treated patients with advanced melanoma (MEL) who received nivolumab (NIVO) monotherapy in a phase I trial. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT001.

Long-term survivors after sorafenib therapy in unresectable hepatocellular carcinoma.

470 Background: Sorafenib is one of the standard therapies for unresectable HCC. Recently, so-called “conversion” cases, who had received curative resection after sorafenib therapy, have been reported sporadically. Here, we investigated outcome of sorafenib treatment and characteristics of long-term survivors. Methods: 1) Thirty-five patients with advanced HCC underwent sorafenib therapy were enrolled. 2) The data of 59 patients from main three hospitals in Tokushima were reviewed to study the characteristics of long-term survivors. Results: 1.) The median treatment period was 3.7mo. The 1-year survival rate was 58%. The rate of partial response was 9% and the rate of stable disease was 34%. These two patients were converted to the surgical resection after sorafenib therapy. Conversion case: 50-year old male with huge unresectable HCC underwent sorafenib therapy as initial treatment. Three months after sorafenib induction, main tumor was shrunken and some intrahepatic metastase were disappeared. Right lobectomy as curative resection could be performed. He has no recurrence for 2 years after surgery. 2.) Of 59 patients, over three-years survivors were four patients (L-group) and twenty-three patients were dead within 1 year after sorafenib induction (S-group). Between the two groups, there was no significant difference in age, gender, liver function, and tumor markers. Only the response to sorafenib was significant factors for long-term survival. Sorafenib administration was continued for more than 3 years in two patients of L-group, but withdrawn in two patients. However, other treatments such as TACE or radiation were done soon after withdrawal. Conclusions: Sorafenib combined with surgical treatment may contribute to improve prognosis of patients with initially unresectable HCC.

Abstract P6-11-11: Characteristics of long-term survivors after brain metastases in breast cancer patients

Abstract Background: Brain metastases (BM) occur in 10%-15% patients of breast cancer patients. It is associated with poor prognosis, requiring great effort to manage local and systemic treatment for BM. The purpose of this study was to analyze the clinico-pathological characteristics of long-term survivors with BM in breast cancer patients. Method: 63 patients with breast cancer BM diagnosed from 2002 to 2010 at the Tokyo Metropolitan Komagome hospital were included. Long–term survival group (Long) was defined as to be consisted of the patients with survival duration more than 36 months after diagnosed with BM and the patients with less than 36 month was into Short-term survival group (Short) in this study. The clinico-pathological characteristics were compared between these two groups. Survival rate and prognostic factors of BM were analyzed by the Kaplan–Meier method and employed by Log–Rank test. Multivariate analysis was performed by the Cox proportional hazard model. Results: Median age of the 63 patients was 53 years (range, 35–78). Median survival time after BM was 12 months (range, 1–168), with about 90 percent of cause of death related to BM (e.g. failure of PS due to BM). As for ER and HER2 status, the number of ER+/HER2- (Luminal:Lum), ER+or-/HER2+ (HER2-enrich:Her2-E), ER-/HER2- (Basal:Bas) were 18, 27, 18, respectively. Among those 63 patients, 11 survived 36 months or more after BM. However, there was no difference in the rate of ER status between Long (55%) and Short (38%), there were significantly high rate of Her2-E case in Long (73%) as compared with Short (29%). Median survival duration after diagnosed with BM of Lum, Her2-E and Bas were 11, 37, 3 months, respectively. Prognosis of Bas was significantly poor (Bas vs. Her2-E p&amp;lt;0.001), and although Her2-E was not significant as compared with ER (p = 0.188), survival time after BM of Her2-E was the tendency to be long. In univariate analysis, Karnofsky performance status (KPS≥70 or &amp;lt;70), HER2 status, disease free interval (from initial diagnosis to first recurrence, DFI≥2years or &amp;lt;2years) had significant impact on survival time after BM. (p = 0.0458, 0.0398, 0.0385, respectively). Meningitis status was a borderline. (p = 0.052) In multivariate analysis, KPS, HER2 status and DFI were significant prognostic factors. (KPS: RR 2.08, 95% CI 1.08-4.07; HER2: RR 2.911, 95% CI 1.396- 6.484; DFI: RR 1.933, 95% CI 0.83-4.102) Conclusions: Although, it was believed that the prognosis after BM was poor, Her2-E BM had a comparatively good prognosis. An existing report supports extension of the survival time after BM by HER2–targeted treatment in BM cases with Her2 positive breast cancer. This newest study reviles the median survival after BM as 37 months in Her2-E BM group, but that of Bas group was only 3 months and this is not improved at all compared with historically reported survival duration (2.4-4.9months). Our reports suggested that the innovation of Her2–targeted treatment leads this surprising improvement of life extension in HER2 positive BM patients but innovation of cytotoxic agents could not contribute toward improvement of clinical outcome in triple negative BM patients. So the necessity of examining the medical treatment of breast cancer BM according to subtype from now on is also considered. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-11.