BACKGROUND:Secondary malignancies are potential complications after high-dose therapy and autologous stem cell transplantation (ASCT). Information on the detailed course of such events is scarce, yet may be essential to minimize the impact of these sequelae. PATIENTS AND METHODS:We regularly monitored 877 patients for up to 31 years after ASCT in our outpatient department. RESULTS:Four-hundred and five patients with malignant lymphoma and 472 patients with multiple myeloma were analysed with a median follow-up from the initial malignant diagnosis of 7.0 years (0.5-35.5), from ASCT of 4.8 years (range 0.2-31.3). Eighty-nine of these patients suffered from 94 invasive secondary malignancies (30 haematologic malignancies, 64 solid tumours). In 29 patients a non-melanoma skin cancer was observed. 31/64 (48%) patients with solid tumours were diagnosed in an early stage of the disease (UICC 0-2) and had a chance of cure. 5% of the patients developed an invasive malignancy within 5 years, 12% within 10 years, 21% within 20 years. Risk factors were advanced age, the diagnosis lymphoma and in lymphoma patients additionally male sex. CONCLUSIONS:Secondary malignancies after ASCT are relatively frequent complications. Our findings suggest that systematic life-long cancer screening after ASCT is essential to improve the prognosis of these adverse events.

Biliary tract cancer is a highly heterogeneous group of gastrointestinal cancers, and the only curative treatment is surgery, which is only applicable at early stages of the malignancy. ADJUBIL, a phase II trial (NCT05239169), aims to evaluate immunotherapy with durvalumab and tremelimumab with or without capecitabine in adjuvant situations for biliary tract cancers. A total of 40 prospective patients will be randomly assigned following surgery, consisting of a two-arm feasibility pilot part with a pick-the-winner design with durvalumab and tremelimumab in combination with or without capecitabine.

Overall survival (Kaplan-Meier Method) by PIK3CA and NRAS status

TPS4187 Background: Despite improvements in multidisciplinary management, patients with biliary tract cancer (BTC) have a poor outcome. Only 20% of patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. Data regarding pure adjuvant chemotherapy in BTC’s are conflicting and the SOC of the western world is currently capecitabine according to the British BILCAP- trial, even though BILCAP was formally negative. Based on the positive data for durvalumab in the TOPAZ- 1 – trial in BTC and for STRIDE- regimen in HCC according to the Himalaya- data, evaluation of IO- combination in the adjuvant setting seems to be promising. Preclinical studies indicate that the antibody combination results in stronger and more durable anti-tumor effects than single therapies by synergistically modulating the immunosuppressive tumor microenvironment which is particularly rich in cholangiocarcinoma. The aim of this study is the assessment of the clinical activity of the anti-PD-L1 (programmed- death 1-ligand) antibody durvalumab and the anti-CTLA-4 (cytotoxic T- lymphocyte-associated antigen 4) antibody tremelimumab in combination with or without capecitabine in patients with respectable BTC in the adjuvant situation. This is a randomized phase II study as a proof-of-concept for a potentially larger research program. Methods: The ADJUBIL trial is an open-label, multicenter phase II study, including patients with BTC after curative surgery with no previous systemic treatment. Patients are randomly assigned to receive tremelimumab (300mg, one dose) plus durvalumab (1500mg every 4 weeks; STRIDE, for a maximum of 12 months), with or without capecitabine (for 8 cycles). Forty evaluable patients will be enrolled in the study (1:1) to receive anticancer treatment until disease recurrence or intolerable toxicities. Primary objective is to assess the anti-tumor activity of the treatment in both arms by the recurrence-free survival rate after 12 months (RFS@12). Secondary endpoints are recurrence-free survival, overall survival, toxicity, and quality of life. Exploratory endpoints: Explore predictive biomarkers for recurrence-free survival and overall survival. Study start of the ADJUBIL trial was in June 2021. By January 2023, 12 centers across Germany have been initiated and a total of 8 out of 40 planned patients (1:1) have been enrolled. The study is currently ongoing. Clinical trial information: EUCTR2021-002389-41 .

Progression-free survival (Kaplan-Meier Method) by PIK3CA and NRAS status

Purpose: The prognosis of patients with peripheral T-cell lymphoma and missing complete remission or relapsing before ASCT is assessed to be unfavourable. The aim of this study is to contribute data to the open question, whether additional radiotherapy improves the outcome. Patients and Methods: Forty-eight patients with peripheral T-cell-lymphoma were treated in our institution with high-dose therapy (usually BEAM protocol) and ASCT (age median 54 years, range 19-77). Twenty-five patients received ASCT in first treatment line, 13 in second line, 10 in third line (all refractory to 2nd-line salvage therapy). Seven of these 48 patients received radiotherapy (36-40 Gy, median 36) after ASCT. Results: Five-year overall survival (OS) and progression-free survival (PFS) after 1st-line ASCT and 2nd-line ASCT were 59% and 50%, respectively, and after 3rd-line ASCT significantly lower with 30% and 30%, respectively. Twenty-one patients achieved a sustained complete remission of 2.7 - 22.7 years (median 5.8). No patient relapsed after radiotherapy. Conclusion: Sustained long-term remissions can be achieved in patients with peripheral T-cell lymphoma following ASCT in first, second or third treatment line. Early irradiation after ASCT can possibly consolidate remission in localized residual or refractory disease.

The prognosis of an early relapse of diffuse large B-cell lymphoma (DLBCL) appears to be poor following autologous stem cell transplantation (ASCT). The aim of this study is to contribute data to the open question on whether additional radiotherapy can improve the outcome. Forty-eight patients with an early relapse (median 4 months after the end of initial immunochemotherapy, range 1–11) of DLBCL have been treated in our institution with high-dose therapy (usually the BEAM protocol) and ASCT since 2008 (median age 61 years, range 28–73). Twenty-three patients received ASCT in a second treatment line, 25 in a third line (19 refractory to second-line salvage therapy, 5 after second relapse). Fifteen of these 48 patients received radiotherapy (36–50 Gy, median 40) of residual masses after ASCT. Three-year overall survival (OS) and progression-free survival (PFS) after second-line ASCT were 61 and 57%, after third-line ASCT 47 and 44%, respectively, without significant differences. A prognostic factor was the International Prognostic Index (IPI) at the start of salvage therapy. Three-year OS and PFS in low-risk patients were 69 and 69%, in low-intermediate-risk 63 and 53%, and in high-intermediate-risk 23 and 23%, respectively (p = 0.033). Twenty-three patients achieved a sustained complete remission (13–146 months, median 62). Sustained long-term remissions can be achieved in patients with early relapse of DLBCL following ASCT in a second or third treatment line, particularly in patients with low- and low-intermediate-risk IPI, following radiotherapy of residual disease after ASCT. Further investigations are required to clarify which patients need an alternative therapy (potentially CAR T‑cells or allogeneic transplantation).

The SCOPE project aimed to better understand practice patterns, identify drivers for treatment goals, and determine third- and fourth-line treatment choices for patients with metastatic colorectal cancer (mCRC). The survey was developed by an expert panel of gastrointestinal oncologists. Questions concerned general practice patterns, and treatment decisions for three hypothetical patient case scenarios. Participants had to routinely manage patients with mCRC. We present results from 629 participants who provided input on patient treatment scenarios (data cutoff: 17/01/2020). Prolonging overall survival (OS; 51%) was the main aim in first line. In third line, quality of life (QOL) was the primary goal (34%). Forty-three percent also cited efficacy-focused goals; 18% and 13% noted prolonging OS and improving progression-free survival as main aims, respectively. For fit and active patients, 89% of respondents considered trifluridine-tipiracil an appropriate third-line treatment; regorafenib (31%) or clinical trial enrollment (29%) were the fourth-line options. For patients with comorbidities and limited caregiver support, trifluridine-tipiracil was the preferred third-line treatment (70%). For KRAS-mutated patients with comorbidities and adverse events who received prior oxaliplatin, 90% considered oxaliplatin rechallenge an unsuitable third-line treatment, mainly due to the risk of cumulative toxicity (75%). In the third/fourth-line settings, trifluridine-tipiracil followed by regorafenib was the most common option (54%); 17% chose regorafenib followed by trifluridine-tipiracil. Efficacy coupled with QOL are important goals in third-line treatment. Daily practice patterns reflect the guideline recommendations in third- and fourth-line settings, with a trend toward using trifluridine-tipiracil versus regorafenib in KRAS-wildtype and KRAS-mutant tumors.

Purpose Treosulfan and fludarabine (Treo/Flu) were successfully introduced into toxicity-reduced conditioning for SCT. However, the risk of post-SCT relapse remains a matter of concern. We report the results of a novel individual treatment approach with Treo/Flu and cytarabine (Treo/Flu/AraC) conditioning prior to allogeneic SCT in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or myeloproliferative neoplasms (MPN). Methods Seventy-seven patients (median age 54 years) at high risk of disease relapse due to unfavorable cytogenetics or failure to achieve complete remission prior to SCT were included. Median follow-up was 3.2 years. Results The 1-, 2- and 3-year RFS rates were 49.4%, 41.7%, and 37.6% and OS rates were 59.3%, 49.3%, and 45.4%, respectively. Cumulative incidence of NRM was 10% at 100 days, 18.8% at 1 year and 20.1% at 2 years. The cumulative incidence of relapse increased from 31% at 1 year to 38.5% after 3 years. The cumulative incidences of engraftment, chimerism, graft-versus-host disease (GvHD) and toxicities were acceptable and comparable with similar patients conditioned with Treo/Flu or FLAMSA-RIC. Conclusion In conclusion, Treo/Flu/AraC provides tolerable, feasible, and effective conditioning for patients with AML, MDS or MPN, even in advanced disease states. The incidence of NRM and relapse is acceptable in this heavily pre-treated population with high-risk disease. Future research will aim to confirm these initial findings and include a larger number of participants in a prospective trial.

BackgroundIn metastatic colorectal cancer (mCRC), there are limited data on associations between early tumor shrinkage (ETS), depth of response (DpR), and patient characteristics.MethodsData from patients with RAS wild-type mCRC who had participated in the PRIME (NCT00364013) and PEAK (NCT00819780) studies were analyzed retrospectively. ETS and DpR were assessed by baseline Köhne category/BRAF status (PRIME) and baseline tumor load (pooled PRIME and PEAK).ResultsAnalysis populations included 436 to 665 patients. Patients’ chances of achieving ETS of 30% or greater were 63.8%, 50.4%, and 41.9% in the low-, medium-, and high-risk Köhne categories, and 21.7% in those with BRAF mutations. Corresponding percentages for the highest DpR classification (71%-100%) were 47.7% (low risk), 23.6% (medium risk), 10.0% (high risk), and 4.2% (BRAF mutant). No clear relationship was observed between baseline tumor load and ETS or DpR. An ETS of 30% or greater and higher DpR values were associated with statistically significant prolongation of median progression-free survival and overall survival.ConclusionPatients with mCRC categorized at baseline by the Köhne criteria as high risk or with BRAF mutations have lower chances of achieving an ETS of 30% or greater or a high DpR. Baseline tumor load was not predictive of ETS or DpR. Favorable ETS or DpR is associated with improved progression-free and overall survival.

Abstract Background Breast cancer (BC) is the most frequent female cancer and preferentially metastasizes to bone. The transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism. However, it is not yet known whether TGIF is associated with BC bone metastasis or patient outcome and thus of potential interest. Methods TGIF expression was analyzed by immunohistochemistry in 1197 formalin-fixed, paraffin-embedded tissue samples from BC patients treated in the GAIN (German Adjuvant Intergroup Node-Positive) study with two adjuvant dose-dense schedules of chemotherapy with or without bisphosphonate ibandronate. TGIF expression was categorized into negative/low and moderate/strong staining. Endpoints were disease-free survival (DFS), overall survival (OS) and time to primary bone metastasis as first site of relapse (TTPBM). Results We found associations of higher TGIF protein expression with smaller tumor size (p = 0.015), well differentiated phenotype (p < 0.001) and estrogen receptor (ER)-positive BC (p < 0.001). Patients with higher TGIF expression levels showed a significantly longer disease-free (DFS: HR 0.75 [95%CI 0.59–0.95], log-rank p = 0.019) and overall survival (OS: HR 0.69 [95%CI 0.50–0.94], log-rank p = 0.019), but no association with TTPBM (HR 0.77 [95%CI 0.51–1.16]; p = 0.213). Univariate analysis in molecular subgroups emphasized that elevated TGIF expression was prognostic for both DFS and OS in ER-positive BC patients (DFS: HR 0.68 [95%CI 0.51–0.91]; log-rank p = 0.009, interaction p = 0.130; OS: HR 0.60 [95%CI 0.41–0.88], log-rank p = 0.008, interaction p = 0.107) and in the HER2-negative subgroup (DFS:HR 0.67 [95%CI 0.50–0.88], log-rank p = 0.004, interaction p = 0.034; OS: HR 0.57 [95%CI 0.40–0.81], log-rank p = 0.002, interaction p = 0.015). Conclusions Our results suggest that moderate to high TGIF expression is a common feature of breast cancer cells and that this is not associated with bone metastases as first site of relapse. However, a reduced expression is linked to tumor progression, especially in HER2-negative breast cancer. Trial registration This clinical trial has been registered with ClinicalTrials.gov ; registration number: NCT00196872 .

Background Patients with carcinoma of unknown primary (CUP) have a dismal prognosis, even when treated with multi-agent chemotherapy. We hypothesised that adding the epidermal growth-factor receptor (EGFR) inhibitor cetuximab to standard first-line chemotherapy with paclitaxel and carboplatin would improve PFS and RR in unfavourable CUP. Methods This open-labelled, multicentre Phase 2 study included patients with unfavourable, untreated adeno- or undifferentiated CUP. Patients were randomised to receive either paclitaxel/carboplatin (group A) or paclitaxel/carboplatin plus cetuximab (group B) every 3 weeks for a maximum of 6 cycles followed by cetuximab maintenance in group B. The primary endpoint was PFS in the two groups. Secondary endpoints were RR, toxicity and overall survival (OS). Results One-hundred-and-fifty patients were randomised (group A = 72, group B = 78). The median PFS and OS for all patients were 3.8 and 8.1 months (95% confidence interval (CI): 2.9–4.8 and 6.8–9.5). There was no significant difference in PFS (3.7 vs 4.6 months, HR 0.98) or OS (8.1 vs 7.4, HR 1.1) between the two treatment groups. Response rate tended to be better for chemotherapy plus cetuximab compared to chemotherapy alone (22% vs 15%). Adverse events grade ≥3 were comparable between the two groups, except for significantly increased skin toxicity in the cetuximab arm. Conclusions Cetuximab plus paclitaxel/carboplatin did not improve PFS, OS and RR in metastatic CUP compared to paclitaxel/carboplatin alone. Addition of cetuximab resulted in additional skin toxicity. Clinical trial registration The study was registered at clinicaltrials.gov as NCT00894569.

705 Background: Using sunitinib (SUN) as the comparator, two out of three recent phase III clinical trials have shown an overall survival (OS) benefit in the alternative treatment arm (Checkmate 214 (C), Keynote 426 (K)). The Javelin 101(J) trial has yet to show a significant improvement. Methods: A cross-study comparison of OS for the sunitinib arms of C, K and J was carried out. Special focus was given to risk group stratification and subsequent therapies. Data from the SUN pivotal trial (SP) was also taken into account. Results: Across the C, K and SP trials, OS was similar at approximately 78%. Despite a lower percentage of favourable risk patients compared to K and SP, an OS of 82% was observed in J. At 18 months, OS survival curves split ranging from 65% ©, 72.1% (K) to 76% (J). OS in the SUN arm in J at 18 months was comparable to OS of Nivolumab/Ipilimumab in C (78%). The rate of subsequent therapies ranged from 34.3% (K), 39.2% (J) to 54% (C) in the SUN arms. At the time of the SP trial almost no subsequent therapy options existed. In the experimental arms, the rate of subsequent therapies was 51.8% ©, 20.5% (K) and 20.8% (J). The existing data give no clear evidence of a correlation between subsequent therapies and OS. However, an analysis of the subsequent therapies/patients discontinuing therapy ratio (ST/DIS) and type of subsequent therapy (PD1/L1 directed or therapy with proven OS benefit (pOS) in randomized trials) in the SUN arms may be more conclusive (see table). The rate of subsequent therapies (ST/DIS) as well as PD(L)1 or pOS therapies were highest in J, followed by K and C. Conclusions: Despite the difficulties of a cross trial comparison, this data should raise awareness of the influence of a more intense subsequent therapy. It points to the necessity to standardize subsequent therapies in 1st line trials if OS is a primary study aim. Given this analysis, it may be pertinent to ask if an optimal or near optimal subsequent therapy following SUN might be equal to a 1st line IO/IO therapy with regards to OS.[Table: see text]

Colorectal cancer is a clinically and molecularly heterogeneous disease. Currently, extended RAS and BRAF mutation testing is obligatory in routine clinical practice before starting any treatment in the metastatic setting. Treatment decision making also includes assessment of the clinical condition of the patient, definition of the treatment goal, and consideration of the primary tumor site. Biological treatment is part of the first-line drug combination unless contraindicated. Mutational status is significantly associated with the outcome of patients and is strongly predictive for anti-EGFR-targeted therapy. The prognosis of RAS mutant CRC is clearly inferior to wild-type cases. RAS remains an elusive target, and specific treatment options are not yet available. Recently, promising results of a direct KRAS G12C inhibitor have been reported; however, further confirmation is needed. The biomarker landscape in mCRC is evolving; new promising markers are awaited with the chance of more precise targeted treatment.

4024 Background: EGFR based combinations and the triplet combination FOLFOXIRI are known to increase response rates compared to doublet combinations. Methods: Patients with colorectal cancer and non-resectable liver metastases were enrolled into the trial. RAS wild type patients were randomised to cetuximab/FOLFIRI or cetuximab/FOLFOXIRI, RAS/BRAF mutant patients were randomised to FOLFOXIRI with or without bevacizumab. The primary endpoint was response. Secondary endpoints included progression free and overall survival. The trial was closed early due to poor recruitment. Results: Between 2014 and 2018, ninety-two pts were enrolled into the study. 54 wild type pts were randomised into cetuximab based treatment with (28 pts) or without (26 pts) oxaliplatin, 38 RAS/BRAF mutant pts were randomised to receive FOLFOXIRI alone (18 pts) or plus bevacizumab (16 pts). Objective response was achieved in 21/26 pts (81 % [95 CI: 61 – 93 %]) with cet/FOLFIRI, 24/28 pts (86 % [95 CI: 67 – 96 %]) with cet / FOLFOXIRI, 13/1 8 pts (72 % [95 CI: 46 – 90 %]) with FOLFOXIRI and 14/20 pts (70 % [95 CI: 46 – 88 %]) with bev/FOLFOXIRI. Two pts with cet/FOLFOXIRI and one pat with FOLFOXIRI achieved CR according to imaging. The median PFS was 12.7 [95 % CI: 7.2 – 18.2], 15.0 [95 % CI: 11.3 – 18.7], 17.5 [95 % CI: 8.0 – 27.1] and 15.0 [95 % CI: 11.4 – 18.5] months with cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI. The median overall survival was 42 mo. [95 % CI: 28 – 55], 55 [95 % CI:41 – 68], 28 [95 % CI: 22 – 36] and 44 [95 % CI: 0 – 94] months with cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI. The frequency of grade ≥ 3 toxicity per arm (cet/FOLFIRI, cet/FOLFOXIRI, FOLFOXIRI and bev/FOLFOXIRI) was 29 %, 46 %, 56 %. 45 % for neutropenia/leukopenia, 11 %, 12 %, 28 %, 25 % for diarrhea and 29 %, 19 %, 6 % and 5 % for skin toxicities. Conclusions: High response rates were observed in patients with colorectal liver metastases with all regimens. The numerically highest response rate was observed in RAS wild type patients treated with cetuximab/FOLFOXIRI. Clinical trial information: NCT01802645 .

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2–1.0%. Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.

4120 Background: Paclitaxel/carboplatin is one of the standard regimens for empiric treatment of patients (pts) with carcinoma with unknown primary (CUP) when a specific therapy is not available. The EGFR antibody cetuximab demonstrated efficacy in several cancer types. Methods: Pts with newly diagnosed non-resectable, undifferentiated or adeno-CUP were randomized to 6 cycles paclitaxel 175 mg/m² and carboplatin AUC 5 every three weeks (arm A) or the same chemotherapy plus cetuximab (400 mg/m², then 250 mg/m² weekly; arm B) at 13 German centres. CUP pts belonging to favorable prognosis groups [i.e. women with isolated peritoneal carcinomatosis or axillary lymph node metastases, men with retroperitoneal lymph nodes, pts with specific tumor entities according to histology / immunohistochemistry] were excluded from the trial. The primary endpoint was progression-free survival (PFS), secondary endpoints were response rate (RR) and overall survival (OS). Results: Between 03/2010 and 03/2017, 72 pts were randomized to arm A and 78 pts to arm B. The median age was 61 years, 84 pts were male (40 and 44 pts in arm A and B). 58 pts had a performance status (PS) of 0 (24 and 34 pts), 89 pts a PS of 1 (47 and 42 pts in arm A and B), and one patient in arm A had a PS of 2. PFS and OS did not differ between arms. The median PFS was 3.7 [95%CI: 3.0 - 4.4] and 4.6 [95%CI: 2.9 - 6.2] months in arms A and B (HR 0.98 [95%CI: 0.70-1.37]), the median OS 8.1 [95%CI: 6.5 - 9.8] and 7.4 [95%CI: 5.1 - 9.6] months in arms A and B, respectively (HR 1.10 [95%CI: 0.77 - 1.56]). There was a statistically non-significant trend towards a higher RR with cetuximab: 11 pts had a partial response in arm A (15% [95%CI: 7.9 - 26%]), and 17 pts in arm B (22% [95%CI: 13%-33%], p = 0.30). Twenty-five pts in each arm had stable disease, and 36 pts in each arm had progressive disease or were not evaluable for response. Conclusions: This study represents one of the largest trials in pts with CUP and demonstrates that randomized trials are feasible in this disorder with high medical need. The outcome of CUP pts in the unfavorable prognosis group was not improved by adding cetuximab to empiric therapy paclitaxel/carboplatin. Clinical trial information: NCT00894569.

Background: Immune cell infiltration in breast cancer is important for the patient's prognosis and response to systemic therapies including immunotherapy. We sought to investigate the prevalence of tumour-infiltrating lymphocytes (TILs) and their association with immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in high-risk, node-positive breast cancer of the adjuvant German Adjuvant Intergroup Node-positive (GAIN-1) trial. Patients and methods: We evaluated TILs by haematoxylin and eosin staining and PD-1 and PD-L1 (SP263 assay) expression by immunohistochemistry in 1318 formalin-fixed, paraffin-mbedded breast carcinomas. The association of TILs with PD-1, PD-L1, molecular intrinsic subtypes, outcome and therapy regimens (dose-dense [dd] epirubicin, paclitaxel and cyclo-phosphamide [EPC] and dd epirubicin, cyclophosphamide, paclitaxel and capecitabine [ECPwX]) was statistically tested. Results: Overall TILs density was significantly associated with the expression of PD-1 and PD-L1 in immune cells (each p < 0.0001) and PD-L1 in tumour cells (p = 0.0051). TILs were more common in triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive tumours (each p < 0.0001). On multivariate Cox regression analyses, patients with breast cancer without TILs had an unfavourable disease-free survival (DFS) in the EPC arm compared with the EC-PwX arm (hazard ratio [HR] = 0.69 [0.44- 1.06], p = 0.0915); but no differences were seen in tumours with TILs (HR = 1.24 [0.92- 1.67], p = 0.1566, interaction p = 0.0336). PD-1-positive immune cells in TNBC were associated with a significantly better DFS (HR=0.50 [0.25-0.99], p=0.0457). PD-L1 expression had no impact on patient outcome. Conclusions: TILs predict the benefit of intensified ddEPC compared with ddEC-PwX therapy in node-positive, high-risk breast cancer. TILs, PD-1 and PD-L1 are linked to each other indicating tumour immunogenicity. Moreover, PD-1epositive immune cells have a positive prognostic impact in TNBC. (C) 2019 Elsevier Ltd. All rights reserved.

820 Background: Prognosis in pts with mCRC is affected by PTL; PTL may also affect the activity of the epidermal growth factor receptor inhibitor Pmab (+ FOLFIRI). Methods: In this phase II, single-arm study (NCT00508404), pts received first-line Pmab+FOLFIRI Q2W until disease progression (PD); primary endpoint: objective response rate (ORR). Analyses included pts with RAS wild-type (WT) mCRC (no mutations in KRAS/ NRAS exons 2, 3 and 4). Baseline demographics/disease characteristics were summarised by PTL and the effect of PTL on outcome was analysed. Early tumour shrinkage (ETS) was defined as a ≥30% reduction in the sum of the longest diameters of measurable target lesions at week 8. Depth of response (DpR) was the maximum % change from baseline to nadir in pts with shrinkage, or the change at PD in pts with no shrinkage. DpR was positive for shrinkage, negative for growth and zero for no change. Progression-free survival (PFS) was analysed by PTL and ETS status. There was no long-term follow-up of overall survival in this study. Results: PTL could be determined in 52/69 (75%) RAS WT pts; 45/52 (87%) had left (L)-sided disease. Pts with L- vs right (R)-sided disease were more likely to have BRAF WT mCRC (91% vs 71%), an ECOG performance status of 0 (56% vs 43%) and liver+other metastases (53% vs 29%). Pts with L- vs R-sided disease had longer median (95% CI) PFS (11.2 [7.6,17.0] vs 7.2 [1.1,19.1] months) and were more likely to experience ETS ≥30% (53% vs 29%). ORR (60% vs 57%), median (95% CI) duration of response (DoR; 13.2 [9.3,47.7] vs 14.3 [3.5,17.3] months), median DpR (61% vs 60%), and resection rates (any: 13% vs 14%; R0: 7% vs 14%) were similar for L- and R-sided pts. ETS ≥30% was associated with improved PFS irrespective of PTL (HR [95% CI] vs ETS < 30%: 0.53 [0.22,1.29] on L; 0.35 [0.03,3.54] on R). Conclusions: These post-hoc data are in line with larger previous studies suggesting improved ETS/PFS with Pmab treatment in RAS WT left-sided mCRC; ORR, DoR and DpR were similar regardless of PTL. No formal conclusions can be drawn regarding the activity of Pmab+FOLFIRI in right-sided mCRC due to the small pt numbers, but ETS may also predict PFS benefit in right-sided disease. Clinical trial information: NCT00508404.