Myleoma (MM) is characterised by frequent disease relapse with the need to introduce further lines of therapy (LoTs). How often all these theoretical options (Dimopoulos et al, 2021) are actually used in “Real World (RW) settings is considered controversial. In recent studies MM patients were found to have attriction rates (ARs) of up to 57% from LoT-1 to LoT-2. (Yong et al, 2016; Fonseca et al, 2020). We aim to assess ARs inside the Austrian Multiple Myeloma Registry and verify treatment patterns in the RW. Methods: Patients with an index diagnosis made between JAN 2009 and AUG 2021 were eligible. Baseline data and treatment patterns were collected. Attrition was defined as being either deceased, progressive without receiving a further LoT, or being lost to follow up for 5 years or more. Results: 571 pts. (n) were identified, of whom 57.1% were men. Median age at FD was 72 years (SD 12.7 y) with a median follow-up of 50.8 months (SD 44.1 m). 507 patients (88.1%) received the first LOT. In 1st LoT 43.2 % (n 219) received stem cell transplantation (SCT), 39.4% (n 200) received maintenance therapy (55.9 % of transplanted patients). The most common treatment in both transplanted and non-transplanted patients was VRD with 20.5 %. AR was nearly constant across LoT 1 to 4 pending between 19.9-27 %. Summarized ARs across all LoTs without SCT was 36% (n 98) compared to 27.7% in the SCT cohort (n 65). A further LoT was instituted in 37.7-48.6 % of pts. in LoT 1-4. Treatment duration (DoT) decreased with a mean of 12.4months in LoT-1 (SD 15.8) to 4 months (SD 15.4) in LoT-5. The exception is LoT-2 with a DoT of 18.4 months (SD 22.1). The latter may be explained by the short observation window with many patients in the 1st line not yet completed. The depth of remission decreases with each subsequent LoT, as PD is present in 10.5% of patients after 1st LoT compared to 29.7% of patients in LoT-5. The risk of attrition decreases by 32.1% in SCT pts. (CI95% 0.679: 0.47-0.99; p=0.045), and follow-up time becomes significantly longer at 53.8 months versus 47.2 months (p=0.007). Patients defined as being victims of attrition were significantly older at 75 years (SD 10.52months, p=0.003). Both factors influence each other, since patients with SCT were significantly younger (64 years, p=0.003). Frontline regimens with a PI and DEX alone increased the risk of falling into AR by 80% (95%CI 1.802:1.09-2.99; p=0.022) compared to triplet and quadruplet inductions. This might mirror the difference between fixed duration vs continuous therapies. Maintenance (nearly uniformly with LEN) in frontline regimens reduces the risk of attrition by 51.5% (95%CI 0,485:0.33-0.73; p<0.001). Conclusions: Overall, our analyses demonstrated ARs significantly lower that than previously reported (Yong et al, 2016; Fonseca et al, 2020). This indicates that issues like drug access and reimbursement might also play major roles with respect to long term results in MM. Our results confirm a negative impact of doublet 1st treatments vs. more intensive ones. The positive impact of SCT on long term prognosis was also confirmed in the RW, in line with multiple clinical trials. The influence of anti-body-based quadruplet inductions cannot be analysed yet but will be assessed in the future. A more detailed breakdown of treatment patterns will be presented.
34 Background: BRAF V600E-mutant metastatic colorectal cancer (mCRC) is associated with a poor prognosis and limited clinical data. Based on results from the BEACON CRC trial, targeted treatment with encorafenib plus cetuximab (E+C) is available as a standard of care for these patients (pts) after prior systemic therapy. Since data from controlled clinical trials are based on a selected patient population, the non-interventional study (NIS) BERING CRC observes a broader patient population in clinical practice. Methods: BERING CRC is the first NIS investigating the use of E+C in clinical practice of BRAF V600E-mutant mCRC treatment after prior systemic therapy in Germany, Austria, and Switzerland. For the present analysis, disease characteristics and treatment data of the initial 81 pts were documented in 44 sites across Germany and Austria between 09/2020 and 04/2022. BERING-CRC is ongoing and aims to enroll up to 300 pts from 126 German, Austrian, and Swiss sites. The study observes pts treated according to the approved respective Summary of Product Characteristics (SmPC). The primary endpoint is the 1-year overall survival rate. Secondary endpoints include efficacy, QoL, and tolerability of E+C. Results: 81 pts were included in this baseline analysis. Median age was 67 years (range 34-88) and 48% were female. 48 pts (59%) were documented with right-sided tumors and for 62% stage IV disease was noted at initial diagnosis. In the metastatic setting, main sites of metastasis were liver, peritoneum, and lung (52%, 32%, and 22% of pts, respectively), with 16% of pts having ≥ 3 sites documented. For 30% of pts, an ECOG performance status (PS) of 0 was documented at baseline assessment (57% ECOG PS 1 or 2). Adjuvant treatment was reported for 22 pts while relapse ≤ 6 months was documented for 10 of them. Consistent with BEACON CRC, adjuvant systemic therapy with relapse within ≤6 months was counted as metastatic 1st line treatment. 91% of pts with adjuvant treatment received chemotherapy alone in this setting. 4 pts (5%) were documented with E+C treatment directly following adjuvant therapy and 55% of all pts with documented first-line treatment (69 pts) received chemotherapy alone (CT), for 35% chemotherapy was combined with targeted therapy (CT+TT), 3% received immunotherapy, and 1% received TT alone. In second-line, 71% of pts with documented treatment received E+C (7% CT, 16% CT+TT). An initial bi-weekly cetuximab dosing was reported for 10% of pts treated with E+C. Conclusions: While the high number of pts with right-sided tumors was in line with previous findings on BRAF V600E-mutant mCRC pts, synchronous metastasis was reported considerably more often in this real-world cohort. As complementation to previous controlled clinical trial data, pts enrolled in BERING-CRC were notably older and presented with higher ECOG PS compared to the pivotal study. Clinical trial information: NCT04673955 .
Background Patients with inflammatory bowel disease (IBD) or chronic liver disease (CLD) on immunosuppressive therapy show poor response to different vaccinations, and were not included in registrational trials for BNT162b2. The aim of our study was to evaluate serologic antibody response and safety of BNT162b2 mRNA vaccine in patients with IBD or CLD on immunosuppressive therapy.
Abstract Introduction Two randomized trials demonstrated a survival benefit of triplet therapy (androgen deprivation therapy [ADT]) plus androgen receptor pathway inhibitor [ARPI] plus docetaxel) over doublet therapy (ADT plus docetaxel) changing treatment strategies in metastatic hormone-sensitive prostate cancer (mHSPC). Patients and methods We conducted the first real-world analysis including 97 mHSPC patients from sixteen Austrian medical centers. 79.4% of patients received abiraterone, 17.5% darolutamide, 2.1% apalutamide and 1% enzalutamide. Baseline characteristics and clinical parameters during triplet therapy were documented. Mann-Whitney-U-Test for continuous or X²-test for categorical variables was used. Variables on progression were tested using logistic regression analysis and tabulated as hazard ratios (HR), 95% confidence interval (CI). Results 83.5% of patients with synchronous and 16.5% with metachronous disease were included, with 83.5% high-volume disease diagnosed by conventional imaging (48.9%) or PSMA PET-CT (51.1%). While docetaxel and ARPI were administered consistent with pivotal trials, prednisolone, prophylactic gCSF and osteoprotective agents were not applied guideline conform in 32.5%, 37% and 24.3% of patients, respectively. Importantly, a non-simultaneous onset of chemotherapy and ARPI, performed in 44.8% of patients, was significantly associated with worse treatment response (p=0.015, HR 0.245). Starting ARPI before chemotherapy was associated with significant higher probability for progression (p=0.023, HR 15.781) than vice versa. Strikingly, 15.6% (abiraterone) and 25.5% (darolutamide) low-volume patients as well as 14.4% (abiraterone) and 17.6% (darolutamide) metachronous patients received triplet therapy. Adverse events (AE) occurred in 61.9% with grade 3-5 in 15% of patient without age-related differences. All patients achieved a PSA decline of 99% and imaging response was confirmed in 88% of abiraterone and 75% of darolutamide patients. Conclusions Triplet therapy arrived in clinical practice primarily for synchronous high-volume mHSPC. Regardless of selected therapy regimen, treatment is highly effective and tolerable. Preferably therapy should start simultaneously, if not possible chemotherapy should be started first. Take Home Massages Triplet therapy consisting of ADT plus ARPI (abiraterone or darolutamide) plus docetaxel is an effective and mostly well tolerable treatment option for mHSPC patients also in the real-world setting especially for synchronous, high-volume patients.
Patients with bone metastases from solid tumors often have additional treatment with bone targeted agents (BTAs) to avoid symptomatic skeletal events (SSEs) such as clinically significant pathological fracture leading toradiation therapy or surgery to the bone, spinal cord compression, or hypercalcemia. The absolute value of BTA treatment in the era of immunotherapy (IO) is unknown. Patients with bone metastases treated with immunotherapy within the Alpine Tumor Immunology Registry were compared based on whether they received an additional BTA such as denosumab or zoledronic acid. The primary endpoint was time to first SSE. Continuous data were summarized as median and range, categorical data using frequency counts and percentages. Kaplan-Meier estimates were used to describe and visualize the effect of categorical variables. One hundred and ninety-seven patients with bone metastases and treatment with immunotherapy such as nivolumab (48 %), pembrolizumab (40 %), atezolizumab (12 %), ipilimumab (9 %) and other immunotherapy (5 %) were included. The most frequent tumor types were lung cancer (50 %), malignant melanoma (11 %), renal cell cancer (10 %) and bladder cancer (9 %), respectively. One hundred and twenty-two patients (62 %) received a BTA treatment (91 % denosumab). The median treatment duration of a BTA was 178 days (min: 1 day, max: 2010 days). Out of the 197 patients, 47 (24 %) experienced at least one SSE, 100 (51 %) had bone pain. Ten of the 122 patients (8 %) receiving a BTA developed osteonecrosis of the jaw (ONJ). The percentage of patients without an SSE at fixed time points was higher if treated with a BTA (e.g., at 6 months, 92 % [95 % CI: 84 % - 96 %] versus 88 % [95 % CI: 77 % - 94 %]), but no significant difference in time to first SSE (HR 0.69; 95 % CI 0.34–1.39, log-rank p = 0.29) or time to first bone pain (HR: 0.85; 95 % CI: 0.51–1.43, p = 0.54) between these two groups could be detected. There were differences in OS between patients treated with a BTA and patients not treated with a BTA (HR: 1.46; 95 % CI: 1.01–2.10, p = 0.043). No significant difference in time to first SSE or bone pain was observed between patients who have received a BTA or not when treated with immunotherapy. Based on these retrospective results the indication of BTAs to reduce SSEs in cancer patients under treatment with immunotherapy needs further evaluation.
e14031 Background: Plastins belong to a subclass of actin-binding proteins known as actin bundling proteins. Plastins family constitute of two isoforms in human as T-plastin (PLS3) and L-plastin (LCP1). Recent in vitro and in vivo studies found plastin genes are overexpressed in colon cancer cells and can lead to increased proliferation, invasion and metastasis. Here we tested the hypothesis whether potential functional tagging polymorphisms in PLS3 (rs6643869, rs5987947, rs2522188) and LCP1 (rs4941543, rs1409429, rs11342) may predict tumor recurrence in adjuvant colon cancer patients. Methods: Either blood or FFPE tissue specimens were obtained from 234 patients (107 females and 127 males; median age 59 years (range 22–78 years)) with stage II (105 patients) or III (129 patients) colon cancer at the University of Southern California/Norris Comprehensive Cancer Center. The median follow-up was 4.4 years. PLS3 and LCP1 SNPs were determined by PCR-RFLP or PCR-based direct sequence. The primary endpoint of the study was time to tumor recurrence (TTR). Results: In univariable analysis, PLS3 rs6643869 and LCP1 rs4941543 were significantly associated with time to tumor recurrence (TTR). Patients with PLS3 AA genotype had shortest median TTR 3.2 years (95% C.I: 1.5-10.7) compared to those with AG or GG genotype, which had median TTR 9.4 years (95% C.I: 5.7-12.2) (p=0.012, log-rank test). Patients with LCP1 CC genotype had longer median TTR 10.7 years (95% C.I: 5.7-16.8+) compared to those with CT and TT genotypes, which had shorter median TTR 4.9 years (95% C.I: 1.4-9.0+)(p=0.040, log-rank test). PLS3 rs6643869 remained significant in the multivariate Cox regression model adjusted by stage and type of adjuvant therapy and stratified by race (p=0.021). Conclusions: Our preliminary results demonstrated that polymorphisms in plastin family genes PLS3 and LCP1 might be potential molecular markers to predict TTR in adjuvant colon cancer. Further large and biomarker embedded trial needed to confirm our findings.
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