Median Follow-up For Overall Survival Research Articles

Outcome of older (\u226570 years) APL patients frontline treated with or without arsenic trioxide\u2014an International Collaborative Study

Data on outcome in older (≥70 years) patients with acute promyelocytic leukemia after treatment with arsenic trioxide (ATO) compared with standard chemotherapy (CTX) is scarce. We evaluated 433 patients (median age, 73.4 years) treated either with ATO+ all-trans retinoic acid (ATO/ATRA; n = 26), CTX/ATRA + ATO during consolidation (CTX/ATRA/ATO; n = 148), or with CTX/ATRA (n = 259). Median follow-up for overall survival (OS) was 4.8 years. Complete remissions (CR) were achieved in 92% with ATO/ATRA and 82% with CTX/ATRA; induction death rates were 8% and 18%, respectively. For analysis of postremission outcomes we combined the ATO/ATRA and CTX/ATRA/ATO groups (ATO/ATRA ± CTX). Cumulative incidence of relapse (CIR) was significantly lower after ATO/ATRA ± CTX compared with CTX/ATRA (P < 0.001). The same held true when restricting the analysis according to the treatment period after the year 2000. OS of patients in CR1 was not different between ATO/ATRA ± CTX compared with CTX/ATRA (P = 0.20). High (>10 × 109/l) white blood cell (WBC) counts at diagnosis were associated with higher CIR (P < 0.001) compared with lower WBC in the CTX/ATRA group, but not in the ATO/ATRA ± CTX group (P = 0.48). ATO, when added to ATRA or CTX/ATRA is feasible and effective in elderly patients for remission induction and consolidation, particularly in patients with high WBC at diagnosis.

Efficacy and safety of PD-1/PD-L1 inhibitors plus nab-paclitaxel for patients with non-small cell lung cancer who have progressed after platinum-based chemotherapy.

Background:Immunotherapy combined with platinum-based chemotherapy is now the standard first-line treatment for non-small cell lung cancer (NSCLC) patients. However, limited evidence exists to show the efficacy of immunotherapy plus taxanes for patients who have progressed after platinum-based chemotherapy.Methods:The immunotherapy naïve patients with metastatic NSCLC who received anti-PD-1/PD-L1 monotherapy or combined with nab-paclitaxel after prior platinum-based chemotherapy from 2015 to 2018 in PLA General Hospital were identified. The progression-free survival, overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety were assessed.Results:Of 57 patients, 40 were treated with anti-PD-1/PD-L1 monotherapy and 17 were treated with anti-PD-1/PD-L1 plus nab-paclitaxel. With a median OS follow-up of 16.3 months, the nab-paclitaxel group showed significantly longer OS compared with the immune monotherapy group (median, 28.6 months versus 15.9 months, log-rank p = 0.020). When adjusted by covariates in COX proportional regression model, both the treatment group [p = 0.009, hazard ratio (HR) 0.361; 95% confidence interval (CI) 0.168–0.773] and performance status (p = 0.003, HR 0.372; 95% CI 0.192–0.721) demonstrated independent association with the longer OS from combination therapy. In addition, ORR was 23.5% (4/17) in the immune checkpoints inhibitors (ICIs) plus nab-paclitaxel group versus 13.5% (5/37) in immune monotherapy group (p = 0.439), with a DCR of 88.2% (15/17) and 59.5% (22/37) (p = 0.034), respectively. The incidence of grade 3/4 adverse events was 23.5% (4/17) in the combination group and 2.5% (1/40) in the immune monotherapy group.Conclusion:PD-1/PD-L1 inhibitor plus nab-paclitaxel resulted in significantly longer OS and higher response versus ICI single agent in metastatic NSCLC patients who have progressed after platinum-based chemotherapy. These findings need to be further explored by prospective studies.

Maintenance Therapy after Second Autologous Stem Cell Transplant in Multiple Myeloma Improves Overall Survival

Introduction: Low dose lenalidomide as a maintenance therapy after the first autologous transplant (autoSCT) has been shown to improve progression free survival (PFS) and possibly overall survival (OS) in standard-risk multiple myeloma (MM). Proteasome inhibitor-based maintenance therapy provides an alternative to lenalidomide and offers PFS and OS advantage in high-risk MM. Most recently oral ixazomib as a maintenance therapy has been shown to reduce the risk of progression by 28%. Despite the advances in maintenance therapy after first autoSCT, no prospective or retrospective studies exist evaluating efficacy of maintenance therapy after second autoSCT. In this retrospective study, we evaluated the impact of maintenance therapy after second autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult MM patients (pts) who received maintenance therapy following second autoSCT. Lenalidomide dose up to 15mg daily and subcutaneous bortezomib 1.3mg/m2 every 2 weeks were considered maintenance therapy. The pts who received higher doses or combinational therapy as maintenance were excluded. We compared outcomes between pts who did and did not receive maintenance therapy following second autoSCT. The objectives were to determine OS, relapse-free survival (RFS), relapse rate and non-relapse mortality (NRM) with maintenance therapy following second autoSCT using Cox regression and competing risk models. Results: Between January 2000 and December 2018, 117 pts underwent second autoSCT and met the inclusion criteria. Of these, 39 received maintenance therapy and 78 did not. Median time between first and second autoSCT was 57 months (range, 4.9-124.2) in the maintenance group and 46 months (range, 3.7-193.5) in the no-maintenance group (p=0.32). Disease status at second autoSCT was complete response (CR) (n=7, 6%), very good partial response (VGPR) (n=22, 19%), partial response (PR) (n=30, 26%), stable (n=21, 18%) and progressive disease (n=32, 27%). Melphalan-based preparative regimen was used in 87% of pts, and BEAM was used in 13% of pts. All pts successfully engrafted and median time to neutrophil and platelet engraftment was 11 and 19 days, respectively. Maintenance therapy after second autoSCT was started at a median day of 105 (range, 62-317). Lenalidomide-based maintenance therapy was commonly used in 23 (59%) pts, and bortezomib as maintenance was used in 16 (41%) pts. Sixteen pts received maintenance therapy after both first and second autoSCT, and 23 received second maintenance only. Median duration of second maintenance therapy was 16 months (range, 8.7-26.5). The best response during maintenance was CR (n=8, 21%), VGPR (n=20, 51%), PR (n=9, 23%), and stable disease (n=2, 5%). Median follow-up for OS was 48 and 60 months in the maintenance and no-maintenance group, respectively. Median OS was not reached in the maintenance group and was 40.8 months in the no-maintenance group (HR 2.32, p=0.02). At 3-year, maintenance group had superior RFS (18% vs 12%; HR 1.65, p=0.03), lower relapse rate (69 vs 81%; SHR 0.58, p=0.02). Median time to progression was 24 months in the maintenance group and 14 months in the no-maintenance group (p=0.04). Although limited by small numbers, we did not observe any impact of cytogenetics at diagnosis on OS and RFS after second autoSCT. RFS was superior with lenalidomide-based maintenance compared to bortezomib-based maintenance (HR 2.17, p=0.05). However, OS was not different. The multivariable analysis revealed that maintenance after second autoSCT was associated with significantly superior OS (HR 0.38, p=0.01), RFS (HR 0.59, p=0.03) and lower relapse rate (SHR 0.63, p=0.04). The common reasons for maintenance therapy discontinuation were disease progression (n=20, 51%), side effects (n=7, 18%), and unknown (n=12, 31%). A total of 10/39 pts who received maintenance therapy and 44/77 pts who did not receive maintenance have died. Conclusion: This is the first study showing efficacy of maintenance therapy after second autoSCT. Maintenance therapy after second autoSCT significantly improved overall and relapsed-free survival and should be considered in all pts after second transplant. Our study also reveals real world practice pattern of using variable dose of maintenance therapy among physicians. Disclosures Deol: Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board.

LBA12 - Updated results of activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601)

BackgroundDurvalumab monotherapy has demonstrated promising objective tumour response (OTR) and safety in advanced endometrial cancer with deficient MMR. We report here updated OTR, progression-free survival (PFS) and overall survival (OS) results based on central pathology MMR review from the PHAEDRA trial. MethodsParticipants (pts) had MMR-proficient (pMMR) or -deficient (dMMR) AEC progressing after 0-3 lines of chemotherapy and were treated with durvalumab 1500mg IV Q4W. The primary endpoint was OTR (complete response [CR] or partial response [PR] by iRECIST). Secondary endpoints included PFS, OS, OTR by RECIST 1.1, adverse events, quality of life, and tertiary translational objectives to determine associations between molecular biomarkers and OTR. Results71 pts with AEC were recruited from Feb 2017 to Sep 2018: 36 dMMR and 35 pMMR based on central MMR review. Median follow-up for OS were 16 vs 21 months in dMMR vs pMMR pts. Median age: 67 (range 36-81); ECOG PS: 0-1 in 96%, and 2 in 4%. Pathology: endometrioid in 94% and 57%; serous in 0% and 31%; grade 3 (most recent histology): 41% and 85% (dMMR and pMMR respectively). Durvalumab was the 1st, 2nd and subsequent line of non-hormonal therapy in 58%, 39%, and 3% pts with dMMR and 9%, 63%, and 29% pts with pMMR. Among dMMR pts, the OTR rate was 47% (17/36, 95% CI 32-63%): 6 CR, 11 PR and 6 stable disease (SD). OTR rate was 57% as 1st line and 38% as 2nd line. Among pMMR pts, the OTR rate was 3% (1/35, 95% CI 1-15%): 1 PR and 10 SD. Median PFS was 5.5 vs 1.8 months in dMMR vs pMMR pts. 12-month OS was 71% vs 51% in dMMR vs pMMR, with median OS not reached for dMMR vs 11.5 months for pMMR participants. ConclusionsDurvalumab monotherapy showed promising activity and safety in AEC with dMMR regardless of prior lines of chemotherapy, but there was limited evidence of activity in AEC with pMMR. Clinical trial identificationACTRN12617000106336. Legal entity responsible for the studyUniversity of Sydney. FundingAstraZeneca. DisclosureY. Antill: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Amgen. M.R. Stockler: Research grant / Funding (institution): As. D. Smith: Honoraria (self): Merck Sharp & Dohme; Shareholder / Stockholder / Stock options: SNP pathology. M.L. Friedlander: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Takeda. P.J. Beale: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche. T. Meniawy: Research grant / Funding (self): AstraZeneca.

Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial

BackgroundSince 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3% (ipilimumab) versus 4.6% (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial. Patients, methods and resultsA total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR] 0.75, 95% confidence interval 0.63–0.88; P < 0.001), DMFS (HR 0.76, 0.64–0.90; P = 0.002) and OS (HR 0.73, 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7% absolute difference at 7 years for OS. The benefit was consistent across subgroups. ConclusionsAdjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.

Update on overall survival in COLUMBUS: A randomized phase III trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in patients with BRAF V600–mutant melanoma.

9512 Background: BRAF/MEK-inhibitor combinations have a central role in the treatment of BRAF V600–mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Because of these meaningful improvements in outcome, mature landmark analyses of PFS and OS, as well as analyses of some prognostic subgroups, require long-term follow-up. Here we report an updated analysis of OS and other endpoints from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 patients with advanced/metastatic BRAF V600‒mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to ENCO 450 mg QD + BINI 45 mg BID (COMBO450) vs VEM 960 mg BID (VEM) or ENCO 300 mg QD (ENCO300). An updated analysis including PFS, OS, objective response rate (ORR), safety and tolerability, and analyses of results by prognostic subgroups including elevated lactate dehydrogenase (LDH) and degree of organ involvement was conducted after an additional 12 months’ follow-up. Results: At data cutoff, there were 116, 113, and 138 deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. Across arms, median follow-up for OS was 48.6 months (mo), with median OS of 33.6 mo (95% CI, 24.4–39.2) for COMBO450, 23.5 mo (95% CI, 19.6–33.6) for ENCO300, and 16.9 mo (95% CI, 14.0–24.5) for VEM. Compared to VEM, COMBO450 decreased the risk of death by 39% (HR, 0.61 [95% CI, 0.48–0.79). Updated median PFS was COMBO450, 14.9 mo (95% CI, 11.0–20.2), ENCO300, 9.6 mo (95% CI, 7.4–14.8), and VEM, 7.3 mo (95% CI, 5.6–8.2). PFS was longer for COMBO450 vs VEM (HR, 0.52 [95% CI, 0.40–0.67). Landmark OS and PFS results, as well as subgroup analyses and updated safety and tolerability, will be presented. Conclusions: Updated PFS and OS results for COMBO 450 from the COLUMBUS trial continue to represent new benchmarks for combined BRAF/MEK-inhibitor combinations for treatment of BRAF V600‒mutated melanoma. Clinical trial information: NCT01909453.

Avelumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma

BackgroundIn a single-group, phase 1b trial, avelumab plus axitinib resulted in objective responses in patients with advanced renal-cell carcinoma. This phase 3 trial involving previously untreated patients with advanced renal-cell carcinoma compared avelumab plus axitinib with the standard-of-care sunitinib.MethodsWe randomly assigned patients in a 1:1 ratio to receive avelumab (10 mg per kilogram of body weight) intravenously every 2 weeks plus axitinib (5 mg) orally twice daily or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The two independent primary end points were progression-free survival and overall survival among patients with programmed death ligand 1 (PD-L1)–positive tumors. A key secondary end point was progression-free survival in the overall population; other end points included objective response and safety.ResultsA total of 886 patients were assigned to receive avelumab plus axitinib (442 patients) or sunitinib (444 patients). Among the 560 patients with PD-L1–positive tumors (63.2%), the median progression-free survival was 13.8 months with avelumab plus axitinib, as compared with 7.2 months with sunitinib (hazard ratio for disease progression or death, 0.61; 95% confidence interval [CI], 0.47 to 0.79; P<0.001); in the overall population, the median progression-free survival was 13.8 months, as compared with 8.4 months (hazard ratio, 0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients with PD-L1–positive tumors, the objective response rate was 55.2% with avelumab plus axitinib and 25.5% with sunitinib; at a median follow-up for overall survival of 11.6 months and 10.7 months in the two groups, 37 patients and 44 patients had died, respectively. Adverse events during treatment occurred in 99.5% of patients in the avelumab-plus-axitinib group and in 99.3% of patients in the sunitinib group; these events were grade 3 or higher in 71.2% and 71.5% of the patients in the respective groups.ConclusionsProgression-free survival was significantly longer with avelumab plus axitinib than with sunitinib among patients who received these agents as first-line treatment for advanced renal-cell carcinoma. (Funded by Pfizer and Merck [Darmstadt, Germany]; JAVELIN Renal 101 ClinicalTrials.gov number, NCT02684006.)

Randomized study evaluating trifluridine/tipiracil (TAS-102) versus + trifluridine/tipiracil + bevacizumab as last-line therapy in patients with chemorefractory unresectable metastatic colorectal cancer (mCRC).

637 Background: Trifluridine/tipiracil (FTD/TPI, also known as TAS-102) is approved for the use in patients with chemorefractory mCRC. Inspired by the encouraging results of a small phase I/II study, C-TASK FORCE, evaluating the combination of FTD/TPI and bevacizumab in chemorefractory mCRC patients (Kuboki et al, 2017), we designed the present randomized trial. Methods: This randomized study enrolled as planned 80 mCRC patients. The main inclusion criteria were: histologically confirmed and chemorefractory mCRC; PD during or after therapy with fluoropyrimidine, irinotecan, oxaliplatin, EGFR-inhibitor (RAS wildtype), and bevacizumab was optional; PS 0-1. In arm A, FTD/TPI was administered orally at the dose of 35 mg/m²/dose bid from day 1 to day 5 and from day 8 to day 12 and in arm B the same dose of FTD/TPI was combined with bevacizumab at a dose of 5 mg/kg on day 1 and on day 15 of a 28-day treatment cycle. The primary endpoint was to increase progression-free survival (PFS) from 1.8 months to 3.8 months. Secondary objectives included overall survival (OS) and safety. Results: Eighty patients with chemorefractory mCRC were randomized from September 2017 to August 2018. The median PFS was significantly improved from 2.6 months (arm A) to 5.9 months (arm B) with a hazard ratio (HR) 0.51 (95% CI, 0.28 to 0.92; P &lt; 0.03) and median OS was significantly improved from 7.3 months (arm A) to 10.3 months (arm B) with HR 0.42 (95% CI, 0.18 to 0.99; P &lt; 0.05). After median follow-up for OS of 5.6 months, 57 patients were alive at September 7th, 2018. Therapy was well tolerated with adverse events as expected, patients receiving FTD/TPI + bevacizumab had more grade 3-4 neutropenia (56% in arm B vs 30% in arm A, p = 0.03) and three patients in arm B (vs zero in arm A ) developed febrile neutropenia. SAEs were observed in 13 (arm A) and 11 patients (arm B), respectively. Conclusions: In patients with chemorefractory mCRC, FTD/TPI + bevacizumab, as compared with FTD/TPI monotherapy, was associated with a significant and clinical relevant improvement in PFS and OS with tolerable toxicity. Clinical trial information: 2016-005241-23.

Abstract CT038: OlympiAD final overall survival: Olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm)

Abstract Background: A significant progression-free survival benefit was shown in OlympiAD (NCT02000622) for patients (pts) with HER2-negative mBC and a gBRCAm receiving olaparib vs TPC (hazard ratio [HR] 0.58; 95% confidence interval [CI], 0.43, 0.80; P&amp;lt;0.001). Interim overall survival (OS) data were reported at primary analysis (46% maturity); prespecified final OS data are now reported. Methods: OlympiAD was a randomized Phase III trial in pts with HER2-negative mBC and a gBRCAm who had received ≤2 lines of chemotherapy for mBC. Randomization (2:1) to olaparib tablet monotherapy (300 mg bid) or single-agent TPC (capecitabine, vinorelbine or eribulin) was stratified by prior chemotherapy (no/yes), prior platinum (no/yes) and receptor status (ER+ and/or PR+ vs TNBC). Data cut-off was 25 September 2017. Results: Of 302 randomized pts, 205 received olaparib and 91 received TPC (6 TPC pts declined treatment). At final OS analysis, 192/302 deaths had occurred (64% maturity). HR for OS in the olaparib vs TPC group was 0.90 (95% CI 0.66, 1.23; P=NS; median 19.3 months [mo] vs 17.1 mo). Median follow-up for OS was 18.9 mo for olaparib vs 15.5 mo in the TPC group. More pts in the TPC group received subsequent therapy with PARP inhibitors, cytotoxic chemotherapy, platinum and hormonal treatment than in the olaparib group. Predefined subgroup analyses are shown for the three stratification factors (Table). SubgroupMedian OS (months)HR95% CINominal P*OlaparibTPCPrior chemotherapy for mBCNo (1L)22.614.70.510.29, 0.900.02Yes (2L/3L)18.817.21.130.79, 1.640.52Prior platinum for BCNo20.319.60.910.64, 1.330.63Yes17.213.30.830.49, 1.450.49Receptor statusER+ and/or PR+21.821.30.860.55, 1.360.51TNBC17.414.90.930.62, 1.430.75*Nominal P-values were calculated using a likelihood ratio test; OS stratification factors were prespecified but not alpha-controlled. 1L, first line; 2L, second line; 3L, third line; BC, breast cancer; ER, estrogen receptor; PR, progesterone receptor; TNBC, triple negative breast cancer CTCAE grade ≥3 adverse events were reported in 38 and 50% of pts receiving olaparib or TPC, respectively, at extended safety analysis. 39 (19%) pts and 15 (7%) pts received olaparib for &amp;gt;18 mo and &amp;gt;24 mo, respectively. Conclusions: At final analysis, median OS was 2.2 mo longer for olaparib monotherapy vs TPC in the overall population (not statistically significant). OlympiAD was not powered to show an OS difference for olaparib vs TPC. Benefit appeared greatest in pts with no prior chemotherapy for mBC (7.9 mo longer median OS in olaparib pts vs TPC). Olaparib safety profile was consistent with primary analysis indicating no relevant cumulative toxicity with extended exposure. Citation Format: Mark E. Robson, Seock-Ah Im, Elżbieta Senkus, Binghe Xu, Susan Domchek, Norikazu Masuda, Suzette Delaloge, Wei Li, Nadine Tung, Anne Armstrong, Wenting Wu, Carsten Goessl, Sarah Runswick, Pierfranco Conte. OlympiAD final overall survival: Olaparib versus chemotherapy treatment of physician's choice (TPC) in patients with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm) [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 CT038.

Tumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data.

Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. Results Data from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P < .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P < .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P < .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); > 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS ( P = .043), but not for the DDFS and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.

Abstract P3-05-06: Prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and its relation to stromal tumor infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC)

Abstract Background: While TNBC remains the most aggressive type of breast cancer (BC), substantial heterogeneity in biology and outcomes exists among TNBC subtypes. Historically, risk stratification of TNBC has been based on anatomic factors such as tumor size, nodal involvement and presence of distant metastases. However, these features alone fail to accurately predict outcomes. Tumor immune infiltration (sTILs) and distribution of immune cell subsets in the perip heral blood (NLR) have emerged as variables reported to be associated with outcomes in TNBC. We sought to evaluate whether NLR and sTILs provided independent prognostic information in TNBC. Methods: From a cohort of 9,982 women who underwent BC surgery at Mayo Clinic, Rochester, MN between Jan 1985 and Dec 2012, we identified 605 centrally-confirmed TNBC tumors. Patients (pts) with prior BC, bilateral BC, non-invasive disease, stage IV, neoadjuvant therapy, endocrine therapy, or adenoid cystic histology were excluded. For eligible tumors, clinical and pathologic variables were evaluated, including peripheral blood NLR and central assessment of sTILs per the 2014 International TILs Working Group recommendations. We calculated the Pearson correlation coefficient (PCC) between NLR and sTILs and constructed Cox Proportional Hazards Models to evaluate their association with invasive-disease free (IDFS) and overall survival (OS). NLR and sTILs were both analyzed as continuous variables. Results: Most pts had T1-2 (95%) and N0-1 disease (86%). Median OS follow-up was 10.6yrs. Median IDFS was 12yrs (95%CI 10.2-16.7) and median OS was 18.8yrs (95%CI 15.6-20.8). NLR and sTILs were available in 408 and 599 pts, respectively. The median NLR and sTIL content were 2.29 (0.14-10.50) and 20% (0-90%), respectively. NLR and sTILs were poorly correlated (PCC 0.0237). On univariate analysis (UVA), a higher NLR was associated with worse IDFS (HR 1.13; 95%CI 1.02-1.26, p=0.02) and OS (HR 1.17; 95%CI 1.04-1.31, p=0.01). Each 1% increment in sTILs was associated with improved IDFS (HR 0.99; 95%CI 0.98-0.99, p&amp;lt;0.001) and OS (HR 0.99, 95%CI 0.98-1.00, p&amp;lt;0.001). Among pts with high sTILs (≥20%), a higher NLR remained significantly associated with worse IDFS (HR 1.21; 95%CI 1.05-1.38, p=0.007) and OS (HR 1.25; 95%CI 1.09-1.44, p=0.001). In contrast, among pts with low sTILs (&amp;lt;20%), NLR was not associated with IDFS (HR 1.07; 95%CI 0.89-1.28, p=0.49) or OS (HR 1.07; 95%CI 0.88-1.30, p=0.49). The interaction test between NLR and sTILs did not reach statistical significance. A multivariate analysis (MVA; including age, menopausal status, histologic subtype, grade, tumor size, nodal stage, Ki-67, NLR, sTILs, adjuvant chemotherapy, type of surgery and adjuvant radiation) showed that sTILs remained independently associated with IDFS (HR 0.99, 95%CI 0.97-1.0, p=0.019) and OS (HR 0.99, 95% CI 0.97-1.0, p=0.044), whereas NLR did not. Conclusions: A lower NLR and a higher sTIL content were each associated with improved IDFS and OS among pts with nonmetastatic TNBC on UVA. However, when evaluated on a MVA, only sTILs remained independently associated with IDFS and OS. Our data suggest that the effect of sTILs on outcomes may not be modified by the NLR. Citation Format: Leon-Ferre RA, Polley M-Y, Liu H, Gilbert J, Cafourek V, Hillman D, Negron V, Boughey JC, Liu MC, Ingle JN, Kalari K, Couch FJ, Visscher DW, Goetz MP. Prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and its relation to stromal tumor infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-06.

Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer.

Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs. The impact of these parameters on invasive disease-free survival (IDFS) and overall survival (OS) was assessed using Cox proportional hazards models. Six hundred five patients met the criteria for TNBC (ER/PR<1% and HER2 negative). Most were T1-2 (95%), N0-1 (86%), grade 3 (88%), and had a Ki-67 >15% (75%). Histologically, 70% were invasive carcinoma of no special type, 16% medullary, 8% metaplastic, and 6% apocrine. The median stromal TIL content was 20%. Four hundred twenty-three (70%) patients received adjuvant chemotherapy. Median OS follow-up was 10.6years. On multivariate analysis, only higher nodal stage, lower TILs, and the absence of adjuvant chemotherapy were associated with worse IDFS and OS. Among systemically untreated patients (n=182), the 5-year IDFS was 69.9% (95% CI 60.7-80.5) [T1a: 82.5% (95% CI 62.8-100), T1b: 67.5% (95% CI 51.9-87.8) and T1c: 67.3% (95% CI 54.9-82.6)], compared to 77.8% (95% CI 68.3-83.6) for systemically treated T1N0. Nodal stage and TILs remained strongly associated with outcomes. In early-stage TNBC, nodal involvement, TILs, and receipt of adjuvant chemotherapy were independently associated with IDFS and OS. In systemically untreated TNBC, TILs remained prognostic and the risk of recurrence or death was substantial, even for T1N0 disease.

Survival profile in breast cancer molecular subtypes without systemic and locoregional treatment.

11599 Background: It is unclear whether survival varies among breast cancer molecular subtypes without systemic and locoregional therapy. This study aims to evaluate the survival profile by molecular subtypes after surgery. Methods: In total, we evaluated 301 women with invasive breast cancer with stage I, II or III disease. Patients were classified into four major breast cancer subtypes by immunohistochemistry/FISH classifiers: luminal-A (ER+ and/or PR+/HER2-), luminal-B (ER+ and/or PR+/HER2+), HER2-enriched (HER2+/ER-/PR-) or basal-like (ER-/PR-/HER2-; triple-negative). Overall survival (OS) was analyzed by Kaplan-Meier analysis, and log-rank test for differences. Association between clinical outcome and subtype adjusting for breast cancer prognostic factors was assessed by multivariable Cox proportional hazards model. Results: All patients did not receive systemic chemotherapy and hormone therapy as well as radiation therapy. Luminal A was the most common subtype (N = 224), followed by basal-like (N = 43), luminal B (N = 21) and HER2-enriched (N = 13). Median follow-up for OS was 197 months (range: 1 – 273 months). Age at diagnosis was statistically different among the subtypes, with basal-like and luminal B having high proportions less than 50 years (P = 0.047). Patients with basal-like and HER2-enriched had more high grade tumors (P &lt; 0.001). Notably, there was no difference in OS among the four subtypes (log-rank P = 0.983). In multivariable analysis, the adjusted hazard ratio (HR) was 1.1 for luminal A vs. luminal B (P = 0.781), 0.62 in luminal A vs. HER2-enriched (P = 0.273), or 0.67 in luminal A vs. basal-like (P = 0.158). In contrast, the adjusted HR were 2.2 in age less than 50 years (P = 0.0017), and 1.1 for number of positive nodes (P = 0.00074). Conclusions: OS, through long-term clinical follow-up, is not significantly different among molecular subtypes if not controlling for other prognostic factors in patients who only received surgery. Age and number of positive nodes are independent prognostic factors in patients with no systemic and locoregional treatments.

Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).

5533 Background: In Study 19 (NCT00753545), a RCT in 265 pts with PSR SOC, the oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) vs placebo (PBO), with the greatest benefit seen in pts with a BRCA1/2 mutation ( BRCAm); an interim overall survival (OS) analysis suggested an advantage for olaparib-treated pts (DCO: Sep 30, 2015; Ledermann et al, 2016). We report a planned final analysis of the long-term benefit of olaparib in pts with PSR SOC in Study 19. Methods: Pts who had received ≥2 prior regimens of platinum-based chemotherapy and were in response to their most recent regimen received olaparib (400 mg bid; capsules) or PBO until disease progression. Retrospective germline or tumor testing resulted in a known BRCAm status for 254/265 pts (96%). Results: At final DCO (May 9, 2016) median OS follow-up was 78.0 months. A long-term treatment benefit and the final hazard ratio (HR) for OS vs PBO (unadjusted for crossover: 13% of PBO pts – full analysis set [FAS]; 23% of PBO pts – BRCAm subgroup) is shown (Table). Details of BRCAwt pts on treatment for ≥6 years will be presented. No new safety signals or changes in olaparib tolerability profile were seen. Conclusions: The Study 19 final analysis shows that olaparib provides clinically significant, long-term treatment benefit in pts with PSR SOC. A durable benefit was seen in ≥10% of BRCAm and BRCAwt pts, who continued to receive and benefit from olaparib for ≥6 years–unprecedented in the relapsed ovarian cancer setting. Olaparib is well tolerated in this pt population and the analysis suggests olaparib confers an OS benefit in BRCAm pts. Clinical trial information: NCT00753545. [Table: see text]

Oncological outcomes in extended intervals time betweeen preoperative chemoradiation with capecitabine and surgery in operable rectal adenocarcinoma: Experience at the National Cancer Institute of Peru.

e15158 Background: The literature reports that longer interval between the end of neoadjuvantchemoradiotherapy (CRT) and surgery is associated with a better rate of pathologic complete response (pCR) in rectal cáncer. Optimal interval remains to be defined. The effects of the extended time intervals on the prognosis are not clear. The objective was to assess whether extended time intervals ( &lt; 8, 8-12, &gt; 12-20 and &gt; 20 weeks) between the end of neoadjuvant CRT and surgery improve overall survival (OS), disease-free survival (DFS) and pathological outcomes Methods: Aretrospective study was conducted for 124 patients with rectal adenocarcinoma without evidence of metástasis (T1-4/N0-2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant CRT with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at National Cancer Institute of Peru. Patients undergoing emergency surgery and R2 resection have been excluded. Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test Results: Of the 124 patients, 72 were women (58.1%). The average age was 59.5 years. All received neoadjuvant CRT. Rates of pCR in the four groups were 25.0%, 10.3%, 7.7% and 17.2%, respectively. No significant difference was found between the association of the radial (P = 0.418) and distal edge (P = 0.487), with time interval groups and similarly with resected (P = 0.308) and compromised nodules (p = 0.783). The median OS follow-up time was 39.5 months and for DFS was 34 months. No significant differences were observed in OS (p = 0.739) and DFS (p = 0.902) according to the four groups studied. Conclusions: We found that amplifying the time interval at 31.9 weeks did not change the mean radial and distal edge. It does not affect the mean of resected and compromised nodules and does not improve overall survival and disease-free survival. The present study is the only one that reports these results at these time intervals. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery.

Abstract S1-08: Prognostic associations of tumor-infiltrating lymphocytes (TIL) in metastatic HER2-positive breast cancer (BC) treated with trastuzumab and pertuzumab: A secondary analysis of the CLEOPATRA study

Abstract Background The presence of stromal TILs (sTILs) is associated with a better prognosis with anti-HER2 therapy in primary HER2-positive BC. The prognostic value of TILs in the advanced setting with pertuzumab-based therapy is unknown. Methods The CLEOPATRA trial randomly assigned 808 patients with metastatic HER2-positive BC to receive pertuzumab or placebo in combination with trastuzumab and docetaxel. We evaluated %TILs using our previously described method. For concordance evaluation, 40 slides from metastatic samples were independently analysed by two pathologists. TILs were examined for associations with clinicopathological factors, progression-free survival (PFS), overall survival (OS), and treatment interactions using Cox regression models fitting sTILs as a continuous variable (per 10%) adjusting for treatment arm, age, estrogen receptor (ER) status, PIK3CA genotype, and visceral vs. non-visceral disease at screening. Results Tumour samples from 678 (84%) participants were available. 519 (76.5%) were archival and 155 (22.9%) were obtained fresh, ≤45 days prior to study treatment start. Median follow-up for OS was 50 months, with 519 PFS events and 358 deaths. 54% of patients were treatment naïve i.e. had not received prior chemotherapy nor trastuzumab. The median sTIL level was 10% (1-95%). sTIL evaluation was highly concordant between pathologists (R=0.93). Fresh vs. archival samples had significantly lower sTILs (10% vs 15%, p=0.0004). sTIL levels significantly differed by ethnicity (15% Asians, 10% white, 5% African-Americans, p=0.0007), but not age (p=0.26). Higher sTILs were observed in ER-negative vs. ER-positive tumors (15% vs 10%, p&amp;lt;0.001). In the whole cohort for PFS, higher sTIL levels trended towards a better outcome independent of treatment (adjusted HR:0.95, 95%CI:0.90-1.00, p=0.06). For OS, the prognostic effect of sTILs reached statistical significance, with each 10% increase in sTILs associated with an 11% reduction in the risk of death (adjusted HR:0.89, 95%CI:0.83-0.96, p=0.001). The prognostic effect was observed independent of treatment arm, ER status, PIK3CA genotype, prior treatment or presence of visceral disease at screening, and in both fresh and archival tissue samples. There was no significant interaction (int) between pertuzumab and sTILs for PFS (Pint=0.4) nor OS (Pint=0.6). There were no significant interactions between pertuzumab and sTILs for OS in subgroups of PIK3CA mutated (Pint=0.2) or PIK3CA WT (Pin=0.2), nor treatment naive (Pint=0.3) vs prior treatment (Pint=0.5). The 5-year estimates of OS according to median ≤10% vs &amp;gt;10% sTILs in the placebo arm were 26% (95%CI:19-37) vs. 39% (95%CI:32-48), while in the pertuzumab arm 42% (95%CI:33-53) vs. 56% (95%CI:47-66) respectively. Conclusion In advanced HER2-positive disease, sTILs are still evident, though at lower levels, but are nevertheless significantly associated with prognosis, with effects stronger for OS than PFS. This suggests that the influence of anti-tumour immunity persists in the advanced first line setting and that enhancement by immunotherapeutic approaches could potentially further improve survival. Citation Format: Luen S, Salgado R, Stephen F, Peter S, Jennifer E-W, Emma C, Astrid K, Sandra SM, Jose B, Stefan M, Sherene L. Prognostic associations of tumor-infiltrating lymphocytes (TIL) in metastatic HER2-positive breast cancer (BC) treated with trastuzumab and pertuzumab: A secondary analysis of the CLEOPATRA study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S1-08.

Nivolumab in metastatic urothelial carcinoma after platinum therapy (CheckMate 275): a multicentre, single-arm, phase 2 trial

Patients with metastatic urothelial carcinoma have a dismal prognosis and few treatment options after first-line chemotherapy. Responses to second-line treatment are uncommon. We assessed nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for safety and activity in patients with metastatic or surgically unresectable urothelial carcinoma whose disease progressed or recurred despite previous treatment with at least one platinum-based chemotherapy regimen. In this multicentre, phase 2, single-arm study, patients aged 18 years or older with metastatic or surgically unresectable locally advanced urothelial carcinoma, measurable disease (according to Response Evaluation Criteria In Solid Tumors v1.1), Eastern Cooperative Oncology Group performance statuses of 0 or 1, and available tumour samples for biomarker analysis received nivolumab 3 mg/kg intravenously every 2 weeks until disease progression and clinical deterioration, unacceptable toxicity, or other protocol-defined reasons. The primary endpoint was overall objective response confirmed by blinded independent review committee in all treated patients and by tumour PD-L1 expression (≥5% and ≥1%). This trial is registered with ClinicalTrials.gov, number NCT02387996, and is completed. Follow-up is still ongoing. Between March 9, 2015, and Oct 16, 2015, 270 patients from 63 sites in 11 countries received nivolumab, and 265 were evaluated for activity. Median follow-up for overall survival was 7·00 months (IQR 2·96-8·77). Confirmed objective response was achieved in 52 (19·6%, 95% CI 15·0-24·9) of 265 patients. Confirmed objective response was achieved in 23 (28·4%, 95% CI 18·9-39·5) of the 81 patients with PD-L1 expression of 5% or greater, 29 (23·8%, 95% CI 16·5-32·3) of the 122 patients with PD-L1 expression of 1% or greater, and 23 (16·1%, 95% CI 10·5-23·1) of the 143 patients with PD-L1 expression of less than 1%. Grade 3-4 treatment-related adverse events occurred in 48 (18%) of 270 patients-most commonly grade 3 fatigue and diarrhoea, which each occurred in five patients. Three deaths were attributed to treatment (pneumonitis, acute respiratory failure, and cardiovascular failure). Nivolumab monotherapy provided meaningful clinical benefit, irrespective of PD-L1 expression, and was associated with an acceptable safety profile in previously treated patients with metastatic or surgically unresectable urothelial carcinoma. Bristol-Myers Squibb.

Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial

Weekly administration of solvent-based paclitaxel is one of the standard second-line chemotherapy regimens for advanced gastric cancer. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) was developed to improve the solubility of paclitaxel and does not need premedication to avoid infusion-related reactions associated with solvent-based paclitaxel. Additionally, higher doses of nab-paclitaxel can be administered over a shorter infusion time and at higher drug concentrations compared with solvent-based paclitaxel. We aimed to investigate the efficacy and safety of nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer. We did a randomised, open-label, non-inferiority, phase 3 trial at 72 institutions in Japan. Patients aged 20 years or older with advanced gastric adenocarcinoma refractory to a fluoropyrimidine-containing first-line chemotherapy regimen, with progressive disease or a relapse fewer than 24 weeks after the final dose of adjuvant chemotherapy were randomly assigned (1:1:1) to receive intravenous nab-paclitaxel (260 mg/m2) every 3 weeks (on day 1 of a 21-day cycle), weekly nab-paclitaxel (100 mg/m2, on days 1, 8, and 15 of a 28-day cycle), or weekly solvent-based paclitaxel (80 mg/m2, on days 1, 8, and 15 of a 28-day cycle). Randomisation was done with the minimisation method, with stratification for previous use of docetaxel, presence of peritoneal metastases, and Eastern Cooperative Oncology Group (ECOG) performance status. The primary endpoint was overall survival in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, with a non-inferiority margin of 1·25 for the hazard ratio. This trial is registered with Japan Pharmaceutical Information Center Clinical Trial, number JapicCTI-132059, and has been completed. Between March 13, 2013, and May 14, 2015, 741 patients were randomly assigned to nab-paclitaxel every 3 weeks (n=247), weekly nab-paclitaxel (n=246), or weekly solvent-based paclitaxel (n=248). Median follow-up for overall survival was 9·99 months (IQR 6·05-15·05). Median overall survival was 10·3 months (95% CI 8·7-11·4) in the group that received in the nab-paclitaxel every 3 weeks, 11·1 months (9·9-13·0) in the weekly nab-paclitaxel group, and 10·9 months (9·4-11·8) in the weekly solvent-based paclitaxel group. Weekly nab-paclitaxel was non-inferior to weekly solvent-based paclitaxel (hazard ratio 0·97, 97·5% CI 0·76-1·23; non-inferiority one-sided p=0·0085), whereas nab-paclitaxel every 3 weeks was not non-inferior to solvent-based paclitaxel (1·06, 95% CI 0·87-1·31; non-inferiority one-sided p=0·062). The main grade 3 or worse adverse drug reactions were neutropenia (158 [65%] of 244 patients in the group that received nab-paclitaxel every 3 weeks vs 99 [41%] of 241 patients in the weekly nab-paclitaxel group vs 71 [29%] of 243 patients in the weekly solvent-based paclitaxel group), peripheral sensory neuropathy (49 [20%] vs six [2%] vs six [2%]), and febrile neutropenia (30 [12%] vs seven [3%] vs two [1%]). Hypersensitivity reactions were less frequent with nab-paclitaxel every 3 weeks (two [1%] patients) and weekly nab-paclitaxel (three [1%] patients) than with weekly solvent-based paclitaxel (13 [5%] patients). Four treatment-related deaths were reported overall (pneumonia in one patient in the group that received nab-paclitaxel every 3 weeks, febrile neutropenia/pneumonia in one patient, and septic shock in one patient in the weekly nab-paclitaxel group, and respiratory disease/interstitial lung disease in one patient in the weekly solvent-based paclitaxel group). As the trial showed that weekly nab-paclitaxel was non-inferior to weekly solvent-based paclitaxel in terms of overall survival, the advantages of the nab-paclitaxel formulation make it a potential regimen for second-line treatment of gastric cancer. Taiho Pharmaceutical.

440O Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm +) NSCLC: overall survival (OS) sdata from LUX-Lung 7 (LL7)

Background The irreversible ErbB family blocker, A, and the reversible EGFR TKI, G, are approved for 1st-line treatment (tx) of advanced EGFRmþ NSCLC. In the Phase IIb LL7 trial, A (40 mg/d) significantly improved PFS (HR 0.73 [95% CI 0.57–0.95], p=0.017), ORR (70 vs 56%, p=0.008) and time to tx failure (TTF; HR 0.73 [0.58–0.92], p=0.007) vs G (250 mg/d) in this setting. Here, we present primary analysis of OS. Methods LL7 assessed A vs G in tx- naı¨ve pts with stage IIIb/IV NSCLC and a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS, TTF and OS; other endpoints included ORR and AEs. Primary OS analysis was planned after_213 OS events and follow-up of≥32 mos. Results At data cut-off (8 Apr 2016), median follow-up for OS was 42.6 mos. Median tx duration was 13.7 (A) vs 11.5 (G) mos. 73%/77% (A/G) of pts who discontinued A/G had_1 subsequent systemic anticancer tx. 46%/56% (A/G) received a subsequent EGFR TKI; 20 (14%)/23 (15%) pts (A/G) received a 3rd-generation EGFR TKI. There was a trend towards improved OS with A vs G (median 27.9 vs 24.5 mos; HR 0.86 [0.66–1.12], p=0.258). Landmark 24-mo and 30-mo OS (A vs G) was 61% vs 51% and 8% vs 40%. Similar OS trends were seen with A vs G in pts with Del19 (30.7 vs 26.4 mos; HR 0.83 [0.58–1.17]) and L858R (25.0 vs 21.2 mos; HR 0.92 [0.62–1.36]) mutations. There was a trend towards improved OS with A vs G in pts who received a 3rd-generation EGFR TKI (NE vs 46.0 mos; HR 0.51 [0.17–1.52]). Consistent OS outcomes were observed across age groups in the A arm (median, mos: 27.9 [≥60 yrs]; 26.7 [≥65 yrs]; 25.1 [≥70 yrs]; 27.9 [≥75 yrs]). 74/62 (46%/39%; A/G) pts survived for >30 mos; of patients who received A,>30-mo survival rates were generally similar across countries of origin and mean average dose received. Similar to the primary analyses, updated PFS, TTF and ORR data were significantly improved with A vs G. The AE profile of A and G was virtually unchanged since the primary analysis. Conclusions In LL7, there was a trend towards improved OS with A vs G that was generally consistent across subgroups. Updated PFS (independent review), TTF and ORR all significantly favored A over G. Clinical trial indentification ClinTrials.gov:NCT01466660/EudraCT:2011-001814-33 (release date: 2011-12-29) Legal entity responsible for the study N/A Funding Boehringer Ingelheim Disclosure K. Park: Advisory board: BI; Corporate-sponsored research: AZ. L. Zhang: Advisory board: AstraZeneca, BMS; Corporate-sponsored research: BMS, Pfizer, Lilly; Honoraria: AZ, Roche, Lilly. V. Hirsh: Advisory board: AstraZeneca, Roche, Pfizer, Merck, Boehringer Ingelheim, Amgen, Lilly; Honoraria: AstraZeneca, Roche, Pfizer, Merck, Boehringer Ingelheim, Amgen, Lilly. K. O'Byrne: Honoraria: Pfizer, Roche, AZD, BI, BMS, MSD, Lilly Oncology, Novartis; Consultancy/Advisory: Pfizer, Roche, AZD, Lilly Oncology, MSD, BI; Travel expenses: Roche, AZD, BI, MSD; Stock: CARP Pharmaceuticals; TCD Ref L002-310-01, US patent 13/601,703 entitled “Global Analysis of Serum mircoRNAs as Potential Biomarkers for Lung Adenocarcinoma [filed 31.08.12); Australian Provisional Patent Number 2015905380 entitled “Nucleic Acid Oligomers and Uses the rof. M. Boyer: Advisory board: Merck, Bristol Myers, Pfizer Corporate-sponsored research: Merck, Bristol Myers, Boehringer Ingelheim, Amgen, Clovis, Astra Zeneca, Eli Lilly, Novartis. J.C-H. Yang: Advisory board (and honoraria TBC): Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astrazeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Innopharma, Merrimack. T. Mok: Stock ownership: Sanomics Ltd; Advisory board: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Aveo & Biodesix, BMS, geneDecode Co., Ltd., Onco Genex Technologies Inc.; Board of directors: IASLC, Chinese Lung Cancer Research Foundation Ltd., Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Therapy Society (HKCTS); Corporate-sponsored research: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS. J. Fan, N. Dodd, A. Märten: Employment: Boehringer Ingelheim. L. Paz-Ares: Honoraria: Pfizer, Boehringer Ing, Lilly, Roche, BMS, MSD, Novartis, Amgen. All other authors have declared no conflicts of interest.

Outcomes of Elderly Patients Who Receive Combined Modality Therapy for Locally Advanced Non–Small-Cell Lung Cancer

BackgroundThe objective of this study was to review our institution's experience among patients with locally advanced non–small-cell lung cancer (LA-NSCLC) treated with chemotherapy and radiation and to determine the prognostic significance of age. Patients and MethodsPatients were included if they underwent sequential or concurrent chemoradiotherapy from 2006 to 2014 for LA-NSCLC. Patients were stratified according to age ≤70 and >70 years. Kaplan–Meier and Cox regression methods were performed to evaluate overall survival (OS) and progression-free survival (PFS). ResultsOne hundred twenty-three patients were identified. Ninety-eight patients were 70 years of age or younger and 25 patients were older than 70 years of age. The median radiotherapy dose was 6660 cGy (range, 3780-7600 cGy). A greater percentage of elderly patients were men, 72% (18 patients) versus 39% (38 patients) (P = .006) and received carboplatin/paclitaxel-based chemotherapy, 60% (15 patients) versus 21% (20 patients) (P < .001). Median follow-up for OS was 25.9 (95% confidence interval [CI], 21.3-33.9) months. There was no difference in the PFS of older patients versus younger patients (hazard ratio [HR], 1.15; P = .64), adjusted for significant covariates. The 1-year PFS rate for patients 70 years of age or younger was 51% (95% CI, 42%-63%) versus 45% (95% CI, 28%-71%) in patients older than 70 years. After adjusting for significant covariates, there was no difference in the OS of older patients compared with younger patients (HR, 1.18; P = .65). The 1-year OS rate for patients 70 years of age or younger was 77% (95% CI, 68%-86%) versus 56% (95% CI, 39%-81%) in patients younger than 70 years. ConclusionChemoradiotherapy is an effective treatment in elderly patients with LA-NSCLC, with outcomes similar to that in younger patients. Appropriately selected elderly patients should be considered for chemoradiation.