Difference In To Treatment Failure Research Articles

Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort.

To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

The efficacy of molecular targeted therapy and nivolumab therapy for metastatic non-clear cell renal cell carcinoma: A retrospective analysis using the Michinoku Japan urological cancer study group database.

To investigate the efficacy of pharmacotherapy for metastatic non-clear cell renal cell carcinoma (nccRCC) in Japanese population. In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular-targeted agents as first-line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database. In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian-target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first-line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75-212 days) and mTORIs (21 days, 95% CI: 9-31 days) didn't differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174-243 days and 33 days, 95% CI: 8-113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p<0.01). There was no significant difference in TTF between the different TKIs in nccRCC group. In addition, no significant difference in TTF for nivolumab was seen between ccRCC and nccRCC groups. The results showed that the efficacy of molecular-targeted agents as first-line therapy was similar oncological outcomes between metastatic nccRCC and ccRCC in Japanese patients. TKIs may be more effective than mTORIs in metastatic nccRCC patients. Nivolumab administration might also be as effective in nccRCC patients as in ccRCC patients in Japanese population.

Clinical characteristics and outcome of PIK3CA mutated hormone receptor positive (HR+), human epidermal growth factor 2 negative (HER2-), advanced breast cancer (BC) treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i): Real world data.

e13078 Background: BC is the most common malignant disease and leading cancer-related cause of death in women. Despite significant achievements in the treatment, advanced BC (aBC) is still an incurable disease. HR+/HER2- subtype accounts for 70% of all BC. One of the most common mutations in BC is the PIK3CA gene mutation which can induce endocrine and chemo- resistance. In early BC, patients (pts) with PIK3CA mutations mostly have better, but in aBC worse prognosis. Standard first-line treatment for HR+/HER2- aBC is a combination of CDK4/6i and endocrine therapy. PIK3CA status is most often assessed in this group of pts and combination of alpelisib - PIK3CA inhibitor and fulvestrant is second-line treatment option in PIK3CA mutated pts. Methods: Medical records of HR+/HER2- aBC pts who started CDK4/6i therapy between 01.08.2018. and 01.10.2020. were analyzed with prior University Hospital Center Zagreb Ethics Committee approval. Demographics, tumor characteristics, clinical presentation and therapy information were collected. Molecular analysis of PIK3CA mutations was performed on tumor tissue samples. Time to treatment failure (TTF) was analyzed using the Kaplan-Meier method and the data cut-off was 31.12.2022. Results: Of the 103 pts with determined PIK3CA status, 45 (43.7%) had a detectable mutation. Median follow-up was 35 months. CDK4/6i were first line therapy in 31 (68.9%) pts with and 29 (50%) pts without PIK3CA mutation. Endocrine resistance, de novo metastatic disease and bone marrow infiltration were more common in PIK3CA mutated subgroup. The incidence of visceral metastases was similar in both groups, whereas liver metastases were more common in the unmutated group. Disease progression was observed in 69 (67%) pts, 28 (40.6%) of whom were PIK3CA mutated. Median TTF in mutated subgroup was 24 months (95% CI 21-33) and 25 months in unmutated subgroup (95% CI 19-36). During the follow-up period, 35 (34%) pts died, 14 (40%) of whom were PIK3CA mutated. Odds ratios in pts with a PIK3CA mutation. Conclusions: There was no relevant difference in TTF between two groups. However, PIK3CA mutated subgroup had more aggressive clinical features - more often presented with bone marrow infiltration and de novo aBC, statistically relevant OR 5.158 and 2.323 respectively, which is related to lower quality of life and highlights the importance of treatment improvement for this subgroup of pts. [Table: see text]

Abstract P2-03-15: Retrospective study using database for the effectiveness of medroxyprogesterone acetate in patients with ER-positive/HER2-negative postmenopausal advanced breast cancer: An additional analysis of the JBCRG-C06 Safari study

Abstract Background: Only old evidence exist to back up the use of medroxyprogesterone acetate (MPA) in endocrine therapy. Therefore, this study aimed to explore the factors that influence the time to treatment failure (TTF) of MPA in real world settings as late-line treatment following aromatase inhibitors and fulvestrant. Methods: This was a cohort study that used the database of the Safari study, on estrogen receptor-positive (ER+) post-menopausal advanced breast cancer previously treated with fulvestrant (UMIN000015168). We created Kaplan-Meier curves for TTF treated with MPA. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the TTF of MPA. Results: Fist, we made Kaplan-Meier curves by treatment line for MPA in TTF analysis population 1 (n = 244), excluding HER2+ and HER2 with unknown status. The median TTF for MPA was 8.2 months (95% CI 5.1–14.9) for first- and second-line treatments, 3.0 months (95% CI 2.5–3.9) for third-line treatment, and 4.1 months (95% CI 3.5–5.0) for fourth or later treatment lines. The first- and second-line treatments had significantly longer TTF than the third-line treatment (P &amp;lt; 0.001) and fourth-line or later treatments (P &amp;lt; 0.001). No difference in TTF was observed between the third and fourth or later treatment lines. Similar results were obtained in the analysis population 2 (n = 203) for TTF, excluding cases in which MPA was considered to have been used in palliative care. The median TTF for MPA was 7.9 months (95% CI, 5.1-16.0) for first- and second-line treatments, 3.0 months (95% CI 2.8–4.6) for third-line treatment, and 4.3 months (95% CI 3.7–5.6) for fourth or later treatment lines. The first- and second-line treatments had significantly longer TTF than the third-line treatment (P &amp;lt; 0.001) and the fourth-line or later treatments (P &amp;lt; 0.001). No difference in TTF was observed between the third and fourth or later treatment lines. Second, Table 1 shows the clinicopathological factors involved in the TTF of MPA. In univariate analysis, long DFI (≥ 6 years), small nuclear or histological grade, and the presence of visceral metastases correlated with significantly long TTF (P &amp;lt; 0.05). Whereas PgR, adjuvant chemotherapy, and adjuvant endocrine therapy did not affect the TTF of patients treated with MPA. However, in the multivariate regression analysis, only longer DFI (≥ 6 years) was correlated with a significantly longer TTF. Third, we compared the clinicopathologic factors in the groups that received MPA as the fourth or later treatment lines and achieved a TTF of more than 1 year with those that did not. There were no characteristic clinicopathological factors distinct between the two groups. Conclusion: In actual clinical practice, patients treated with MPA alone as the fourth or subsequent treatment lines showed a TTF of 4 months, suggesting that there is merit in using MPA even in late treatment lines, especially in patients with long DFI and those who are difficult to treat with other antineoplastic agents. Table 1. Univariate and Multivariate analyses to investigate association between clinicopathological factors and TTF of MPA (n=170) Citation Format: Kaho Utsunomiya, Hidetoshi Kawaguchi, Yutaka Yamamoto, Shigehira Saji, Norikazu Masuda, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Shoichiro Ohtani, Nobuaki Sato, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Toshinari Yamashita, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Retrospective study using database for the effectiveness of medroxyprogesterone acetate in patients with ER-positive/HER2-negative postmenopausal advanced breast cancer: An additional analysis of the JBCRG-C06 Safari study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-15.

Predictors of therapeutic efficacy of anamorelin in patients with gastric, pancreatic, and colorectal cancer.

331 Background: Anamorelin is a highly selective ghrelin receptor agonist that improves appetite and increases lean body mass in patients (pts) with cachexia. We aimed to investigate the predictors of therapeutic efficacy of anamorelin in pts with gastrointestinal cancer. Methods: This retrospective study included pts with gastric cancer (GC), pancreatic cancer (PC), and colorectal cancer (CRC) treated with anamorelin at our institution between May 2021 and July 2022. Glasgow Prognostic Score (GPS) was defined as follows: GPS 0: CRP≤1.0 (mg/dL) and Alb≥3.5 (g/dL), GPS 1: either CRP&gt;1.0 or Alb&lt;3.5, GPS 2: CRP&gt;1.0 and Alb&lt;3.5. The endpoints were the response rate (RR) of anamorelin and time to treatment failure (TTF). RR was defined as the proportion of appetite improvement within 3 weeks of anamorelin, and TTF was defined as the time from the start of anamorelin to discontinuation due to insufficient response. The observation period lasted 12 weeks. RR was analyzed by univariate and multivariate logistic regression analyses, and TTF by competing risk analysis. In the competing analysis, discontinuation of anamorelin due to worse symptoms, hospital transfer for poor condition, and adverse events (AEs) were considered as competing events. Results: A total of 103 pts were included; median age was 70 (range: 37–84) years, 61 pts (59%) were men, and 17 pts (17%) had an ECOG PS ≥2. The proportion of GC/PC/CRC were 43/42/16%; median body mass index (BMI) was 19.9 (range: 14.4–26.8) kg/m2. The treatment line for 1st/2nd/≥3rd/others was 51/13/14/22%, respectively. GPS was 0/1/2 in 21/30/49%, respectively. Except for treatment line, there were no significant differences in patient characteristics according to the cancer type. A total of 12 pts discontinued treatment owing to AEs (nausea, 3; epigastric distress, 2; fatigue, 2; poor physical condition, 2; staggering, 1; pulsation, 1; diarrhea, 1 pts). The RR was 42%. Pts with GPS 2 had less improvement in appetite than those with GPS 0 or 1 (26% vs. 56%, adjusted odds ratio [95% confidence interval (95%CI)]:0.22 [0.07–0.69], p=0.009). The RR of pts with GC, PC, and CRC were 44%, 42%, and 41%, respectively. The cumulative incidence of discontinuation of anamorelin after 12 weeks was higher in pts with GPS 2 than in those with GPS 0 or 1 (46% vs. 30%). The TTF in pts with GPS 2 was significantly shorter than that in pts with a GPS 0 or 1 (adjusted subdistributional hazard ratio [95%CI]:2.80 [1.37–5.72], p=0.005). There was no statistically significant difference in TTF by cancer type, although TTF was shorter in GC and PC than in CRC. Other factors, including age, sex, baseline BMI, ECOG PS, lines of therapy, and cancer type did not correlate with RR and TTF. Conclusions: In pts with a GPS of 0 or 1, anamorelin showed better appetite improvement and a longer treatment effect than in those with GPS 2. TTF was shorter in pts with GC and PC; therefore, the timing of use should be carefully considered.

Comparison of outcomes for Hispanic and non-Hispanic patients with advanced renal cell carcinoma in the International Metastatic Renal Cell Carcinoma Database.

6590 Background: Epidemiologic studies suggest that Hispanic patients with renal cell carcinoma (RCC) have worse outcomes than non-Hispanic White patients (NHW). It is unclear if this disparity is related to inherent biological differences or patients’ social determinants of health (SDOH). Utilizing the International Metastatic Renal Cell Carcinoma Database (IMDC) of patients with RCC primarily receiving care at academic medical centers, we investigated outcomes of Hispanic and NHW patients with advanced RCC. Methods: Eligible patients included patients who self-reported being non-Black Hispanic or NHW with locally advanced or metastatic RCC initiating systemic therapy. The primary endpoint was overall survival (OS) and secondary endpoint was time to treatment failure (TTF) for the first-line therapy. Kaplan Meier curves were constructed for OS and TTF. Cox regression was used to estimate hazard ratios (HR) adjusted for confounding variables. Results: The cohort included 1,563 patients, of which 181 (11.6%) were Hispanic. Most patients were male (74%) with clear cell histology (82%). IMDC risk groups were 18%, 58%, 24% for favorable, intermediate, and poor risk, respectively, and were similar by ethnic groups. Compared to NHW, Hispanic patients were younger at diagnosis (median 57 vs 59 years, p = 0.036), less likely to have &gt; 1 metastatic site (61% vs 77%, p &lt; 0.001) and bone metastases (24% vs 33%, p = 0.009). 1,178 patients (124 Hispanic vs. 1,054 NWH) received treatment before 2018, 385 patients (57 Hispanic vs. 328 NWH) received treatment during or after 2018. With regards to first line therapy, the majority received tyrosine kinase inhibitor (TKI) monotherapy (70%), 10% received immunotherapy (IO) + IO, 9% received TKI + IO, 4% received IO monotherapy, and 8% received other treatments. Median TTF was 7.8 months (95% Confidence Interval (CI): 6.2-9.0) in Hispanic patients and 7.5 months (95% CI: 6.9-8.1) in NHW patients. On multivariable analysis, there was no significant difference in TTF between Hispanic and NHW patients (HR 1.05, 95% CI: 0.89-1.25, p = 0.558). Significant predictors of TTF were presence of unfavorable site of metastases, histology, IMDC risk group, and therapy type. Median OS was 38.0 months (95% CI: 28.1-59.2) in Hispanic patients and 35.7 months (95% CI: 31.9-39.2) in NHW patients. On multivariable analysis, there was no significant difference in OS between Hispanic and NHW patients (HR 1.07, 95% CI: 0.87-1.32, p = 0.544). Significant predictors of OS were number of metastatic sites, presence of unfavorable metastasis, histology, IMDC risk group, and therapy type. Conclusions: In this analysis, we did not detect a difference in OS or TTF for Hispanic patients with RCC. Our data suggest that access to care (as available in a tertiary cancer hospital) can mitigate the historic difference in outcomes in Hispanic versus NWH patients.

Comparative Effectiveness of Abiraterone and Enzalutamide in Patients With Metastatic Castration-Resistant Prostate Cancer in Taiwan.

BackgroundAbiraterone and enzalutamide are widely used as first-line treatment for metastatic castration-resistant prostate cancer (mCRPC); however, their efficacy in mCRPC has been inconsistently demonstrated in other outcome studies from real-world databases. The aim of our study was to assess the comparative effectiveness of abiraterone and enzalutamide in patients with mCRPC using real-world data from Taiwan.MethodsThis retrospective cohort population-based study included patients identified in the Taiwan National Health Insurance Research Database who had been diagnosed with mCRPC and who had taken abiraterone or enzalutamide between December 2014 and August 2017. The study’s outcome evaluated the differences in overall survival (OS) and time to treatment failure (TTF) between abiraterone and enzalutamide over a 15-month follow-up period. The patients were followed from the index date to when the outcome occurred, to December 31, 2018, or to the patients’ withdrawal from the National Health Insurance program. The estimated relative treatment effects of abiraterone and enzalutamide on OS and TTF were adjusted by the inverse probability of treatment weighting (IPTW) using the Kaplan–Meier method and a Cox proportional hazards model.ResultsThe abiraterone and enzalutamide groups consisted of 1,046 and 118 patients, respectively. After IPTW adjustment, 1,164 patients in the abiraterone group and 1,158 in the enzalutamide group underwent an outcome evaluation. Enzalutamide showed a similar OS rate to that of abiraterone (57.58% vs. 49.51%, p = 0.095 by log-rank test). Enzalutamide significantly reduced the risk of death for mCRPC when compared with abiraterone [adjusted hazard ratio (aHR), 0.828; 95% CI 0.731–0.938]. However, similar results were not observed in the TTF outcomes (63.84% vs. 67.79%, p = 0.2651 by log-rank test; aHR, 0.902; 95% CI 0.812–1.002).ConclusionIn conclusion, enzalutamide was associated with better OS for mCRPC than abiraterone in the Taiwan population. Our study showed that there was no statistically significant difference in TTF between enzalutamide and abiraterone. Studies with longer surveillance of enzalutamide and abiraterone using real-world databases are needed.

Addition of High-Dose Cytarabine to Immunochemotherapy before Autologous Stem-Cell Transplantation in Patients Aged 65 Years or Younger with Mantle Cell Lymphoma (MCL Younger): A Long-Term Follow-up of the Randomized, Open-Label, Phase 3 Trial of the European Mantle Cell Lymphoma Network

Addition of High-Dose Cytarabine to Immunochemotherapy before Autologous Stem-Cell Transplantation in Patients Aged 65 Years or Younger with Mantle Cell Lymphoma (MCL Younger): A Long-Term Follow-up of the Randomized, Open-Label, Phase 3 Trial of the European Mantle Cell Lymphoma Network

Impact of Tumor Suppressor Gene Co-Mutations on Differential Response to EGFR TKI Therapy in EGFR L858R and Exon 19 Deletion Lung Cancer

BackgroundIn most studies, patients with EGFR L858R mutant non-small cell lung cancer (NSCLC) have a shorter duration of response to EGFR tyrosine kinase inhibitor (TKI) therapy than do patients with EGFR exon 19 deletion NSCLC. The role that co-mutations play in this observation is unknown. MethodsWe performed a single-institution retrospective analysis of patients with EGFR-mutant NSCLC (exon 19 deletion or L858R mutation) who received frontline EGFR TKI for metastatic disease between 2014 and 2019, and who had STAMP next-generation sequencing (NGS), a 130-gene platform. Time to treatment failure (TTF) and overall survival were calculated using Cox models adjusted for age, race, and brain metastases. Co-mutations in key tumor suppressor genes (TP53, RB1, KEAP1, CDKN2A, or CTNNB1) were identified and their effects on outcomes were evaluated. Analyses were stratified according to receipt of osimertinib versus nonosimertinib as frontline EGFR TKI. ResultsOf 137 patients, 72 (57%) had EGFR exon 19 deletions and 65 (43%) had EGFR L858R mutations. Median TTF and OS on frontline TKI was shorter for the L858R cohort versus the exon 19 deletion cohort in univariate analysis. In adjusted models, this difference persisted for TTF but was no longer significant for OS. The difference in TTF in L858R mutant tumors was driven by the presence of co-mutations in key tumor suppressor genes. ConclusionPatients with metastatic NSCLC with mutations in EGFR L858R had shorter TTF on frontline TKI compared to patients with EGFR exon 19 deletions. Co-mutations in tumor suppressor genes may play an important role in the differential response to TKI therapy.

Effect of high-dose corticosteroid use on efficacy of immune checkpoint inhibitors in patients with renal cell carcinoma (RCC).

4583 Background: The use of High-Dose Corticosteroids (HDC) has been linked to poor outcomes in patients with lung cancer treated with immune checkpoint inhibitors (ICIs) (Ricciuti B, JCO, 2019). There is no data on the effect of HDC on renal cell carcinoma patients (RCC) treated with immunotherapy. We hypothesized that HDC use would be associated with worse outcomes in RCC patients receiving ICIs. Methods: This study evaluated a retrospective cohort of patients with RCC at Dana-Farber Cancer Institute in Boston, MA. Clinical information including demographics, IMDC risk score, RCC histology, steroid administration, ICI regimen, line of therapy, time to treatment failure (TTF) and overall survival (OS) were collected. Patients were divided into those receiving HDC (prednisone ≥10 mg or equivalent for ≥ 1 week, HDC group) or not receiving HDC (No-HDC group). HDC administration was evaluated in relation to TTF and OS in a univariate analysis (Log-rank test) and a multivariate analysis (Cox regression). Results: 190 patients with RCC receiving ICIs were included, with a median age of 59 years. HDC were administered to 56 patients and 134 patients received no (N= 116) or only low-dose (N=18) steroids. In the HDC group, 40 patients received steroids for immune-related adverse events, 8 for other cancer-related indications, and 8 for non-oncological indications. There was no difference in TTF between the HDC and No-HDC groups (12-mo TTF rate: 34.8 vs. 32.3%, respectively; log-rank p=0.65). Similarly, there was no difference in OS between the HDC and No-HDC groups (36-mo OS rate: 56.7 vs. 62.4%, respectively; log-rank p=0.97). After adjusting for IMDC risk group, RCC histology, ICI regimen type, and line of therapy, TTF and OS did not differ in the HDC group as compared to No-HDC group (HR=1.14 [95%CI: 0.80-1.62], p=0.44 and HR=1.17 [95%CI: 0.65-2.11], p=0.59, respectively). Conclusions: In this retrospective study of patients with RCC treated with ICIs, administration of high-dose corticosteroids was not associated with worse outcomes.[Table: see text]

Maintenance durvalumab after first-line platinum-based chemotherapy in advanced oesophago-gastric (OG) adenocarcinoma: Results from the PLATFORM trial.

4015 Background: PLATFORM is a prospective, open-label, multicentre, adaptive phase II trial assessing maintenance therapy in patients (pts) with OG adenocarcinoma after platinum-based first-line induction chemotherapy. HER2 negative pts were initially randomised 1:1:1:1:1 to surveillance (A1), capecitabine (A2), durvalumab (A3), with rucaparib (A4) and capecitabine + ramucirumab (A5) added later as per adaptive design. Here we report the primary analysis of durvalumab maintenance vs. surveillance. Methods: Pts were randomised upon achieving response or stable disease following 18 weeks of platinum-based chemotherapy and were stratified by region, disease extent and performance status. A1 pts had 4 weekly surveillance visits and A3 pts received 10mg/kg durvalumab iv Q2W. Target accrual was 154 pts/arm; however, A3 was closed prematurely after cessation of industry support. The primary endpoint was progression-free survival (PFS) from randomisation post induction chemotherapy to disease progression according to RECIST 1.1 criteria, or death. Secondary endpoints were time to treatment failure (TTF), objective response rate (ORR), overall survival (OS) and toxicity. Survival analyses according to PD-L1 using the combined positive score (CPS, Ventana SP263 assay) was conducted. Results: A total of 205 pts were concurrently randomised into A1 (n = 100) and A3 (n = 105). At data cut-off (02 Feb 2021), median follow up was 24.2 months [95% confidence interval (CI) 21.6-36.8]. There was no significant difference in PFS between A1 and A3 [median PFS: 3.2 vs. 4.7 months (hazard ratio (HR) 0.79 (95% CI 0.59-1.06, p = 0.122) respectively]. Median OS was 11.4 vs. 11.3 months (HR 0.92, 95% CI 0.66-1.27, p = 0.60) in A1 and A3 respectively and no significant difference in TTF was detected between both arms (median TTF: 3.2 vs. 3.5 months (HR 0.92, 95% CI 0.69-1.23, p = 0.558)]. ORR was 6% in A3 (n = 2 complete and n = 4 partial responses) whereas no radiological responses were seen in A1. PD-L1 results were available for 76 pts in A1 and 77 pts in A3. PFS was comparable between subgroups using the PD-L1 CPS thresholds of ≥1, ≥5 and ≥10. The safety population consisted of 199 pts (A1: 98 pts and A3: 101 pts). Grade ≥3 treatment-related adverse events were reported in 18% of A3 pts and no new safety signals were identified. Conclusions: Although a survival advantage was not seen with maintenance durvalumab compared to surveillance, a subset of patients who received durvalumab demonstrated incremental radiological responses. Exploratory analysis of PD-L1 expression was not associated with improved survival outcomes. Clinical trial information: NCT02678182.

The prognostic significance of homologous recombination repair pathway alterations in metastatic hormone-sensitive prostate cancer.

150 Background: Little is known about the clinical course of patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC) who harbor alterations in the homologous recombination repair (HRR) pathway. Here, we examine the outcomes of men with mHSPC with HRR alterations. Methods: Single center, retrospective analysis of men with mHSPC who underwent next generation sequencing from 2015-2020. The primary endpoint was to assess the time from diagnosis of mHSPC to onset of castrate resistance (mCRPC), as defined by PCWG3 criteria, in pts with HRR alterations vs wild type (WT). Both somatic and germline HRR alterations were permitted. Univariate and multivariate Cox regression were used to assess the effect of HRR alterations on time to mCRPC. Secondary endpoints included time to mCRPC stratified by HRR gene and time to treatment failure (TTF) in HRR altered vs WT pts, stratified by therapy. Results: We identified 151 men with mHSPC for the study. Median age was 66 years and 62% (n = 93) had de novo metastatic disease. 25% (n = 37) had HRR alterations detected and the most common alterations were in BRCA2 (n = 15), ATM (n = 10), CDK12 (n = 7). 78.4% (n = 29) of alterations were somatic and 13.5% (n = 5) of pts had co-alterations in 2 HRR genes. Time to mCRPC was significantly decreased in pts with HRR alterations vs WT (12.7 vs 16.1 mos, HR- 1.95, p- 0.02). In multivariate analysis, the effect of HRR alterations on time to mCRPC remained statistically significant when adjusting for age, mHSPC therapy, presence of visceral metastases, and PSA (adjusted HR- 1.69, p-0.02). Stratified by individual HRR gene, pts with BRCA2, CDK12, or co-occurring alterations had significantly decreased time to mCRPC compared to other HRR alterations (Table). In terms of mHSPC therapy, 45.7% were treated with ADT alone, 27.8% with an androgen receptor signaling inhibitor (ARSI), and 26.5% with docetaxel. TTF was inferior in HRR altered vs WT pts (10.8 vs 13.8 mos, p-0.004, HR- 1.84). Stratified by therapy, TTF was inferior in HRR altered vs WT pts treated with ADT alone (8.9 vs 13.3 mos, p- 0.019, HR-1.94) and there was no significant difference in TTF in HRR altered vs WT pts treated with either the addition of an ARSI or docetaxel. Conclusions: HRR alterations are associated with worsened outcomes in mHSPC patients. Given the established role of PARP inhibitors in mCRPC, these data highlight an opportunity to explore the use of PARP inhibitors in mHSPC to potentially improve outcomes. [Table: see text]

Differential efficacy of Osimertinib in EGFR T790M positive non-small cell lung cancer by metastatic site

Abstract Background Osimertinib is a standard treatment for non-small cell lung cancer(NSCLC) with common and T790M EGFR mutation and efficacy for brain metastasis is reported. However there are only a few reports regarding efficacy or other metastatic sites such as pleural effusion, bone metastasis, and pulmonary metastasis. Methods We retrospectively analyzed efficacy of osimertinib in 84 patients who had NSCLC with common and T790M EGFR mutation and received osimertinib at our hospital between March 2016 to December 2018. Results Baseline characteristics of the 84 patients is as follows. There were 33 males and 51 females. The median age was 64 years. ECOG PS was 0, 1 or 2 in 19 (22.6%), 56 (66.7%) and 9 (10.7%) patients, respectively. Twenty three patients (27.4%) had pleural effusions, 32 patients (38.1%) had brain metastasis, 42 patients (50%) had bone metastasis, and 58 patients (69.0%) had pulmonary metastasis. For all patients, the response of osimertinib were 48 PR (57.1%), 24 SD (28.6%), 6 PD (7.1%), 6 NE (7.1%). Median time to treatment failure (TTF) was significantly shorter in patients with pleural effusions than those without (9.5 vs 11.1 months, respectively, p = 0.01). Regarding bone metastasis, brain metastasis, or lung metastasis, there was no significant difference in TTF (p = 0.52, p = 0.11, p = 0.88, respectively). Conclusion Osimertinib might be less potent for pleural effusion.

First-line (1L) immuno-oncology (IO) combination therapies in metastatic renal cell carcinoma (mRCC): Preliminary results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).

584 Background: In mRCC, ipilimumab and nivolumab (ipi-nivo) is a 1L treatment option. Recent data have also shown efficacy of 1L PD(L)1-VEGF (PV) inhibitor combinations. The efficacy of these two strategies has not been compared. Methods: Using the IMDC dataset, patients (pts) treated with any 1L PV combination were compared to those treated with ipi-nivo. Multivariable Cox regression analysis was performed to control for imbalances in IMDC risk factors. Results: 164 pts received 1L IO combination therapy: 104 treated with PV combinations and 60 with ipi-nivo. Baseline characteristics and IMDC risk factors were comparable between groups (Table). When comparing PV combinations vs ipi-nivo, 1L response rates (RR) were 30% vs 39% (p = 0.29), time to treatment failure (TTF) was 13.2 (95% CI 8.3-16.1) vs 8.5 months (95% CI 5.7-14.0, p = 0.31), and median overall survival (OS) was not reached (NR) (95% CI 19.7-NR) vs NR (95% CI 27.6-NR, p = 0.39). When adjusted for IMDC risk factors, the hazard ratio (HR) for TTF was 0.77 (95% CI 0.44-1.35, p = 0.36) and the HR for death was 0.94 (95% CI 0.33-2.71, p = 0.91). Similar results were seen when restricting the cohort to IMDC intermediate/poor risk pts only. In pts receiving subsequent VEGF TKI monotherapy, second-line (2L) RR (13% vs 45%, p = 0.07) and TTF (5.5 vs 5.4 months, p = 0.80) for PV combinations (n = 15) vs ipi-nivo (n = 20) were not significantly different. Conclusions: There does not appear to be a superior 1L IO combination strategy in mRCC, as PV combinations and ipi-nivo have comparable RR, TTF and OS. Although there is a trend towards differences in RR, there does not appear to be a significant difference in TTF for patients receiving 2L VEGF TKI therapy. [Table: see text]

M7-FLIPI Not Valid in Follicular Lymphoma Patients with First-Line Rituximab Chemo-Free Therapy

BackgroundIn patients with follicular lymphoma (FL) the clinical international prognostic index FLIPI is well established, but recently the impact of a number of gene mutations was evaluated. The m7-FLIPI prognostic model, derived from the FLIPI score combined with ECOG and the mutational status of seven specific genes, was shown to stratify FL patients into “low-risk” and “high-risk” with respect to 5-year failure-free survival after first-line immunochemotherapy (R-CHOP or R-CVP) (Pastore, Lancet Oncol 2015). The Nordic Lymphoma Group (NLG) performed two trials (accrual 1998-1999 and 2002-2008, respectively) including a total of 439 patients with symptomatic/progressing indolent B-cell lymphoma (79% FL) randomized 1:1 to treatment with single rituximab or rituximab plus interferon-α2a (Kimby, Leuk Lymphoma 2008, 2015). A follow-up study after 10 years found 36% still chemotherapy-free (Lockmer, JCO 2018).Aim: As part of a long-term follow-up of we aimed to investigate whether the m7-FLIPI prognostic model could be validated in a FL patient cohort treated with first-line-immunotherapy only.MethodsFresh-frozen diagnostic lymph node biopsies with sufficient material for gene sequencing were available from 88 patients with verified FL grades 1-3a and 7 patients with indolent B-cell lymphoma not otherwise specified. A targeted Lymphochip panel including the seven genes of the m7-FLIPI, EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP and CARD11, was used. Clinical data were retrieved from the databases of the two trials and from follow-up medical records. Variables assessed included all post-trial therapies, the last dates of follow-up and causes of death. The m7-FLIPI score was calculated according to the published sum of predictor algorithm with respect to high-risk FLIPI, ECOG >1 and occurrence of non-silent mutations. Time to treatment failure (TTF), the primary endpoint, was defined as the interval between start of trial therapy and either initiation of new lymphoma therapy due to relapse or intolerance, or death from any cause. TTF was chosen rather than the date of stable or progressive disease described in the Pastore report, as the date of new therapy is less affected by assessment frequency and quality. The Pastore cut-off score of ≥ 0.84 for discrimination between the m7-FLIPI high- vs low-risk group was applied. TTF and overall survival (OS) were estimated with the Kaplan-Meier method and the log-rank test applied for comparison between risk groups.ResultsMutational status was obtained from 95 patients, four of them with two biopsies each. In two of the doublets mutations differed between samples in which case the earliest dated samples was chosen for risk analyses. Three patients (two FL) could not be risk-stratified according to the m7-FLIPI score due to missing clinical information. Patient characteristics and gene mutations are shown in Table 1. The mutation frequency distribution was broadly similar to the Pastore report cohorts, mutations in the epigenetic modifier CREBBP by far the most common. With a median follow-up after randomization of 10.6 (range 0.6-18.3) years, 72 (76%) patients were alive. Of all, 28% had never required any new therapy, and 39% had not required any chemotherapy. For 13 out of 23 patients the cause of death was lymphoma-related i.e. due to progression of disease or complications of therapy. No difference in TTF nor OS was found between the m7-FLIPI high- vs low-risk group (fig 1a-b), but in the high-risk FLIPI group OS was shorter (fig 1d). Mutation in the EZH2 gene, coding for the catalytic subunit of a histone methyltransferase, was associated with longer TTF (p=0.04) also within FLIPI risk groups but not with OS (p=0.63).ConclusionThe m7-FLIPI prognostic clinicogenetic model was not valid in our cohort with FL patients treated with only immunotherapy. Mutation in the gene EZH2 was associated with longer TTF and high-risk FLIPI with shorter OS. [Display omitted] DisclosuresWahlin:Gilead: Consultancy, Honoraria, Research Funding; Roche: Research Funding. Kimby:AbbVie: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Roche: Honoraria.

Osimertinib for EGFR-Mutant Lung Cancer with Brain Metastases: Results from a Single-Center Retrospective Study.

Osimertinib is a third-generation tyrosine kinase inhibitor, initially approved for epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) with T790M acquired resistance, and now approved in the first-line setting. However, data supporting the use of osimertinib in untreated brain metastases are limited, although it has established central nervous system (CNS) activity. Our study compares the clinical outcomes of patients experiencing progressing brain metastases treated with cranial irradiation and osimertinib with those treated with osimertinib alone. Forty patients who were treated with osimertinib at the Stanford Cancer Center from November 2015 to December 2016 were identified by searching an electronic medical record database. Eleven patients had progressing brain metastases and did not receive radiation (group A), 9 patients had progressing brain metastases and received radiation when starting osimertinib (group B), and 20 patients had stable brain metastases at the time of initiating osimertinib (group C). Patient and disease characteristics, radiographic responses, and survival outcomes were evaluated retrospectively for the three groups. The CNS response rate was 32.3%. Median time to treatment failure (TTF), overall progression-free survival (PFS), and overall survival (OS) were 10.0 months (95% confidence interval [CI], 4.5-11.8), 8.8 months (95% CI, 6.2-12.1), and 16.2 months, respectively. Median TTF was 15.1 months for group A (95% CI, 1.7-28.5), 7.7 months for group B (95% CI, 0-15.5), and 10.7 months for group C (95% CI, 9.0-12.5). The median PFS was 8.8 months for group A (95% CI, 4.3-13.4), not reached for group B, and 8.4 months for group C (95% CI, 5.6-11.1). The median OS was not reached for group A and C, and was 16.2 months for group B. There was no apparent difference in TTF, PFS, or OS between the three groups. Receiving radiation prior to starting osimertinib for patients with progressing brain metastases did not prolong TTF, PFS, or OS in our series. To minimize the risks of radiation-related toxicity, delaying radiation could be considered for some patients with EGFR-mutant NSCLC with brain metastases who initially respond to osimertinib in the second-line setting. Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor recently approved for the first-line treatment of EGFR-mutant non-small cell lung cancer. Although it appears to have central nervous system (CNS) activity, most clinical trials have excluded patients with untreated, progressing brain metastases. This study included patients with stable and progressing CNS metastases treated with osimertinib and found no apparent differences in median time to treatment failure, time to progression, and overall survival in patients who received osimertinib alone compared with those who received osimertinib and radiosurgery. This may support a clinician's decision to defer radiation for selected patients with untreated brain metastases who are candidates for osimertinib therapy.

Treatment Duration and Side Effect Profile of Long-Term Use of Intravitreal Preservative-Free Triamcinolone Acetonide in Uveitis

Noninfectious uveitis has been treated historically with corticosteroid therapy in varying doses and routes. Triesence, a preservative-free sterile formulation of triamcinolone acetonide, has been used in a wide spectrum of ocular pathologies, but there have been few large studies validating its dosing or detailing long-term side effects in uveitic disease. The primary aim of this study was to describe the relative duration of action and side effects of 2 doses of preservative-free intravitreal triamcinolone acetonide (PF-IVTA) in uveitis. Retrospective, comparative consecutive case series. Charts of all patients receiving PF-IVTA (2mg or 4mg) in a defined time period (2012-2014) at the Cole Eye Institute were examined for patient demographics, time to treatment failure (TTF), use of systemic immunosuppression, use of intraocular pressure-lowering therapies, date of cataract surgery and glaucoma filtration surgery, and adverse events. The final data set examined 514 injections in 214 eyes. Mean duration of follow-up was 1.5 years. There was similar demographic distribution between eyes that received 2mg PF-IVTA only and eyes that received a combination of 4+ 2mg PF-IVTA. No statistically significant difference in TTF between injection dosages was observed. There was a higher incidence of glaucoma filtering surgery and cataract surgery in eyes that received 4+ 2mg PF-IVTA as well as a shorter time to glaucoma surgery, when compared to eyes that received 2mg PF-IVTA alone. This retrospective study supports that 2mg PF-IVTA displayed noninferior treatment duration to 4mg PF-IVTA, and may carry a significantly lower side-effect profile of cataract development and glaucoma filtering surgery.

P3.02b-060 Comparative Analysis of the Efficacy of Three 1st/2nd Generation EGFR-TKIs for EGFR Mutated NSCLC in Clinical Practice: Topic: EGFR Clinical

EGFR-TKIs show promising anti-tumor activities for EGFR mutated NSCLC, and three EGFR-TKIs, gefitinib (GEF), erlotinib (ERL) and afatinib (AFA), are available for treatment of NSCLC harboring an EGFR mutation in first-line settings in Japan. Which EGFR-TKI is optimal for first-line therapy in clinical practice, however, is not yet known. We reviewed all patients who were diagnosed with EGFR mutated NSCLC between January 2010 and April 2016 at two institutions in Mie, Japan. The aim of this retrospective study was to evaluate three EGFR-TKIs using time to treatment failure (TTF), overall survival (OS) and the response rate (RR) in clinical practice. TTF analysis was conducted on all patients, while OS analysis was conducted on patients in stages 3B or 4. Either chi-square statistics, or a Fisher’s exact test was used where appropriate to compare proportions among groups. Survival curves were calculated using the Kaplan-Meier method, and were compared using the log-rank test. A total of 310 patients were diagnosed with EGFR mutated NSCLC in the three institutions. Of the 310 patients, 145 patients treated with EGFR-TKI were enrolled. The median age was 70 years old (range 37-95), 88 patients (62.9%) were female and 97 patients were never-smokers. Almost all patients (96.3%) were diagnosed with adenocarcinoma, with 52.4% diagnosed with Ex19 deletion, and 44.8% diagnosed with Ex21 L858R. 82 patients received gefitinib as the first EGFR-TKI, while 35 patients received erlotinib, and the remaining 28 patients received afatinib. The efficacy assessment demonstrated that there was no significant difference in TTF (9.4m; GEF, 9.3m; ERL, 14.1m; AFA), OS (24.8m; GEF, 22.7m; ERL, NR; AFA), and RR among the three EGFR-TKIs. Subgroup analysis indicated that adenocarcinoma, being a never-smoker, and the presence of a major mutation were predictive factors for a longer TTF of EGFR-TKI therapy. OS of patients with brain metastasis (BM) was significantly shorter than those without BM. (p=0.018). This study demonstrated a tendency of afatinib to be superior, however, there was no significant difference in TTF and OS among the three EGFR-TKIs as of submission. These results indicated that all EGFR-TKIs had equal clinical benefit at presence, with a potential superiority for afatinib. Further prospective investigations are warranted to evaluate the efficacy of these three EGFR-TKIs in clinical practice to confirm these results.

Changes in Uninvolved Immunoglobulins during Multiple Myeloma Therapy

▪BackgroundSuppression of uninvolved immunoglobulins is a common finding in multiple myeloma and the preservation of uninvolved immunoglobulins at diagnosis is associated with improved progression-free and overall survival. However, little is known about the impact of myeloma treatment on levels of uninvolved immunoglobulins, and the link between changes in uninvolved immunoglobulins during therapy and treatment response, disease progression and survival.MethodsWe identified patients who received therapy for newly diagnosed multiple myeloma at our institution between 2001 and 2014, and who had data available on absolute lymphocyte count (ALC) and quantitative uninvolved immunoglobulins (Ig) before commencing treatment. The ALC and levels of uninvolved Ig after 4 cycles of therapy were abstracted from the electronic medical record; patients who switched or stopped treatment, or died, before this time point were excluded. To assess change in ALC, the percentage difference in ALC between baseline and 4 cycles was calculated; for uninvolved Ig, the average of the percentage difference between baseline and 4 cycles for each uninvolved Ig (IgA and IgM for IgG myeloma, IgG and IgM for IgA myeloma, IgG and IgA for IgM and IgD myeloma, and IgG, IgM and IgA for light-chain only myeloma) was calculated. Treatment response at 4 cycles was retrospectively assigned according to International Myeloma Working Group criteria. Time to treatment failure (TTF) was defined as time from start of initial therapy to start of next line of therapy or death (if no additional treatment was received). A landmark analysis was used to calculate overall survival (OS) from the date of follow-up after 4 cycles of therapy. The Kruskal-Wallis, Chi-Square, and log rank tests were used to detect differences in medians, proportions, and survival times respectively.ResultsA total of 421 patients were included in this analysis. The median age was 63 years (range 33-91), 254 patients (60.3%) were male and median follow-up was 6.5 years (95% CI 5.6-7.3); the vast majority of patients had IgG (n=247 [58.7%]), IgA (n=98 [23.3%]) or light-chain only myeloma (n=68 [16.2%]). First line therapy comprised of pulse-dose dexamethasone (DEX, n=92 [21.9%]), lenalidomide-dexamethasone (RD, n=176 [41.8%]), bortezomib-dexamethasone (VD, n=22 [5.2%]), bortezomib-cyclophosphamide-dexamethasone (VCD, n=84 [20.0%]), and bortezomib-lenalidomide-dexamethasone (VRD, n=47 [11.2%]).Across the entire cohort, the median change in ALC and uninvolved Ig after 4 cycles of treatment was -11.0% (range: -92.7 to +718.8) and +9.0% (-77.7 to +1094.4) respectively; treatment with VCD was associated with the greatest median declines in ALC (DEX: -0.1%; RD: -9.9%; VD: -20.8%; VCD: -40.9%; VRD: -15.3%) and uninvolved Ig (DEX: -0.5%; RD: +15.5%; VD: +44.0%; VCD: -14.0%; VRD: +76.0%, both p<0.001). Conversion from suppression to normalization of the primary uninvolved Ig (IgA in IgG myeloma, and IgG in all other myeloma types) after 4 cycles was seen more frequently with the use of RD (13.1%) and VRD (12.8%) compared to DEX (4.7%), VCD (1.3%), or VD (4.8%), χ2=21.8, p=0.040. When considering only patients in whom the primary uninvolved Ig remained suppressed between baseline and 4 cycles, a ≥25% reduction in the primary uninvolved Ig occurred more frequently with the use of DEX (51.5%) and VCD (34.5%) compared to RD (24.8%), VD (23.5%) or VRD (25.7%), χ2=15.1, p=0.005 (Table 1).Although an average reduction in uninvolved Ig between baseline and 4 cycles (ΔIg<0) was independently associated with a lower likelihood of achieving very good partial response (VGPR) of better on multivariate analysis adjusting for age, sex and treatment regimen (OR=0.40 [0.24-0.63], p<0.001), there were no differences in TTF (2.0yrs vs. 2.0yrs, p=0.783) or OS (8.0yrs vs. 8.0yrs, p=0.721) between patients with ΔIg<0 (n=169) and those with ΔIg≥0 (n=222).ConclusionsMyeloma treatments produce differential impacts on immune parameters, with VCD causing the greatest reduction in lymphocytes and uninvolved Ig, implying general targeting of plasma cells, in comparison to lenalidomide, which appeared to be more tumor-specific with relative sparing of lymphocytes and uninvolved Ig. While an average decrease in uninvolved Ig was an independent predictor of a lower likelihood of achieving VGPR or better after 4 cycles of therapy, it was not associated with a shorter TTF or poorer OS. [Display omitted] DisclosuresKumar:BMS: Consultancy; Glycomimetics: Consultancy; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Kesios: Consultancy; Millennium: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Research Funding. Dispenzieri:GSK: Membership on an entity's Board of Directors or advisory committees; Prothena: Membership on an entity's Board of Directors or advisory committees; pfizer: Research Funding; Jannsen: Research Funding; Alnylam: Research Funding; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kapoor:Amgen: Research Funding; Celgene: Research Funding; Takeda: Research Funding. Bergsagel:Amgen, BMS, Novartis, Incyte: Consultancy; Novartis: Research Funding.

Real-world data on nivolumab treatment of non-small cell lung cancer

Background: Checkpoint inhibitors have proven effectiveness in clinical trials for non-small cell lung cancer (NSCLC) patients, but if this is congruent with routine patient care is discussed. We present real-world experience with the PD1-inhibitor nivolumab in NSCLC.Patients and methods: Patients with NSCLC were considered eligible for nivolumab treatment after one or more lines of chemotherapy, and when in reasonable performance status (PS) [Eastern Cooperative Oncology Group (ECOG) < 3]. Treatment was given according to guidelines in the two phase III studies, CA209017 and CA209057. Response evaluation was done according to Recist 1.1, and treatment given until unequivocal progression or intolerable toxicity.Results: Fifty-eight patients (30 females) commenced therapy in the period June–August 2015. Median age was 64.6 years (range 32.3–88.2). Twenty-four patients had squamous cell carcinoma and 32 adenocarcinoma, 38 had received two or more prior lines of therapy. Fourteen cases (24%) were in ECOG PS 2. After a medium observation time of 14.3 months, 13 (22%) are still in treatment. Median time to treatment failure (TTF) was 4.0 months, 34% were off treatment during the first two months. Median overall survival (OS) is 11.7 months. There was no difference in TTF or OS among patients with squamous versus non-squamous histology or between 1 versus >1 prior line of therapy. Four patients (7%) were off treatment due to toxicity, none were grade 4 or 5.Conclusion: Nivolumab treatment outside clinical trials seems to perform as expected.