Later-line Treatment Research Articles

300P Real-world efficacy and safety of anlotinib in combination with PD-1/PD-L1 inhibitors as first-line or second-line treatment in advanced non-small cell lung cancer

Antiangiogenic therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC. The purpose of this study is to investigate the efficacy and safety of anlotinib in combination with PD-1/PD-L1 inhibitors as first-line or second-line treatment in advanced non-small cell lung cancer in the real-world setting.

Impact of T790M Mutation Status on Later-Line Osimertinib Treatment in Non-Small Cell Lung Cancer Patients.

Simple SummaryOsimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) designed to overcome acquired T790M resistance mutations in non-small cell lung cancer (NSCLC). A total of 172 patients with advanced NSCLC treated with osimertinib following frontline EGFR-TKIs were retrospectively reviewed and divided into three groups based on the T790M status (positive, negative, or unknown T790M). The study confirmed the greater efficacy of later-line osimertinib for NSCLC with acquired T790M mutation than for NSCLC without acquired T790M mutation. Detection of the T790M mutation after frontline treatment (first- and second-generation EGFR-TKI) is crucial for prolonging the survival of NSCLC patients harboring EGFR mutation. Osimertinib may be considered an option for NSCLC with unknown T790M mutations, as a certain subpopulation may benefit from osimertinib.Background: Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) designed to overcome acquired T790M resistance mutations in non-small cell lung cancer (NSCLC). However, the efficacy of osimertinib in patients without acquired T790M mutations has not been well studied. This study aimed to evaluate the efficacy of osimertinib in patients treated with first- and second-generation EGFR-TKIs followed by later-line osimertinib treatment. Patients: The clinical data and survival outcomes of 172 patients with advanced NSCLC treated with osimertinib following frontline EGFR-TKIs at Chang Gung Memorial Hospital from 2014 to 2018 were retrospectively reviewed. T790M mutations were detected using tissue sequencing and/or liquid biopsy. Results: A total of 172 EGFR-mutated NSCLC patients treated with frontline EGFR-TKI therapy followed by later-line osimertinib were enrolled in the current study and divided into three groups based on the T790M status (positive, negative, or unknown T790M). Patients with NSCLC harboring acquired T790M mutation treated with osimertinib had the best objective response rate (ORR) (52.6%, 25.0%, and 32.0%, p = 0.044), disease control rate (DCR) (79.3%, 41.7%, and 68.0%, p = 0.011), and progression-free survival (PFS, median PFS, 12.6, 3.1, 10.4 months, p = 0.001) among the three groups (positive, negative, and unknown T790M, respectively). However, a marked difference was found between positive and negative T790M mutations but not between positive and unknown T790M mutations. Univariate analysis was performed to identify potential prognostic factors for PFS in 172 patients treated with osimertinib. Lung metastasis (p < 0.001), brain metastasis (p < 0.009), number of metastatic sites (p < 0.001), PFS with frontline EGFR-TKIs (p = 0.03), and T790M status (p = 0.006) were identified as prognostic factors for PFS with osimertinib. Multivariate analysis showed that lung metastasis (p < 0.001) and PFS with frontline EGFR-TKIs and T790M status were independent prognostic factors. Conclusion: This study confirmed the greater efficacy of later-line osimertinib for NSCLC with acquired T790M mutation than for NSCLC without acquired T790M mutation. Detection of the T790M mutation after frontline treatment (first- and second-generation EGFR-TKI) is crucial for prolonging the survival of NSCLC patients harboring EGFR mutation. Osimertinib may be considered an option for NSCLC with unknown T790M mutations, as a certain subpopulation may benefit from osimertinib.

Clinical actionability and utilization of next-generation sequencing for prostate cancer in a changing treatment landscape

BackgroundUntil recently there were no genome-directed therapies (GDTs) requiring next-generation sequencing (NGS) in prostate cancer. We examined whether the US approval of poly-(ADP-ribose) polymerase (PARP) inhibitors in May 2020 influenced the actionability and utilization of NGS in patients with prostate cancer.MethodsThis was a single-center, retrospective study including men with prostate cancer who received NGS testing from a single lab between 7/11/2018-7/6/2021. Clinical and testing data were derived from the electronic medical record.ResultsThere were 346 patients with prostate cancer and qualifying NGS testing during the study period. Overall, 55 patients (15.9%) had qualifying homologous recombination repair (HRR) alterations for PARP inhibitor treatment. A greater proportion of alterations were actionable post-approval compared to pre-approval (22.7% vs 0%, Chi-squared p&amp;lt;0.001). 9 patients received olaparib during the study period. Patients receiving NGS testing after the PARP inhibitor approval were more likely to have metastatic disease than patients sequenced before the approval (74.2% vs. 41.1% Chi-squared p&amp;lt;0.001). Only 10.4% of patients with metastatic prostate cancer received NGS testing within 30 days of diagnosis. NGS testing was performed after a median of 1 prior line of systemic therapy. The median number of days between metastatic diagnosis and NGS testing was 196 (Q1-Q3: 54-832). The median time from NGS testing to the next treatment was 255 days (95% CI 151-300). These characteristics were not significantly different before or after the PARP inhibitor approval.ConclusionIn this single-center cohort, the approval of PARP inhibitors for later-line treatment of metastatic prostate cancer increased the actionability of NGS findings but did not lead to earlier use of NGS testing.

Efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients with pretreated HER2-positive advanced metastatic breast cancer: results from a randomized, open-label, multicenter, phase II bridging study.

Trastuzumab is the recommended first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) patients in China, but therapeutic resistance to trastuzumab and other early-line treatments is common and late-line treatment options are limited. Derived from the same murine precursor antibody, margetuximab has enhanced anti-tumor activity compared with trastuzumab and may be an effective late-line treatment. However, data regarding the use of margetuximab in pre-treated Chinese patients are scarce. This study aimed to evaluate the efficacy and safety of margetuximab plus chemotherapy vs. trastuzumab plus chemotherapy in Chinese patients, and to determine whether the results are consistent with the clinical benefit of margetuximab observed in the pivotal global phase III study. In this randomized, open-label, multicenter, phase II bridging study, eligible Chinese patients pretreated with ≥2 lines of anti-HER2 therapies were randomized 1:1 by stratified block randomization to margetuximab (15 mg/kg over at least 120 minutes) or trastuzumab (6 mg/kg over at least 30 minutes), each administered intravenously once every 21-day cycle and plus chemotherapy. Disease assessment was conducted once every two treatment cycles (6 weeks ± 7 days). The primary endpoint was progression-free survival (PFS) by blinded independent central review (BICR). Secondary endpoints included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), clinical benefit rate (CBR), and the incidence and severity of treatment-emergent adverse events (TEAEs). Between February 4, 2020 and February 23, 2021, 123 patients were randomized to the margetuximab (n=62) and trastuzumab (n=61) arms. Among them, 15 and 7 patients, respectively, were still on study treatment as of data cut-off (September 3, 2021). Overall, 99.2% were female, median age was 53 years old. All patients were pretreated with trastuzumab, and 83.7% and 25.2%, respectively, were pretreated with tyrosine kinase inhibitors (TKIs) and pertuzumab. Baseline characteristics were numerically balanced between arms. BICR-assessed median PFS (mPFS) was 5.5 months in the margetuximab arm and 4.1 months in the trastuzumab arm, with a hazard ratio (HR) of 0.69 [95% confidence interval (CI): 0.43-1.12], which met the consistency criterion (HR <0.88) for bridging success. Median investigator-assessed PFS was 5.5 months in the margetuximab arm and 4.0 months in the trastuzumab arm (HR =0.63; 95% CI: 0.41-0.96). Median OS (mOS) was not yet reached. Both ORR and CBR were greater in the margetuximab arm (25.5% vs. 12.5%; 32.7% vs. 14.3%). Safety results were numerically comparable between the two arms. Anti-HER2 treatment-related infusion-related reactions (IRRs) were more common in the margetuximab arm than in the trastuzumab arm (12.9% vs. 1.7%). All IRRs could be resolved. Margetuximab was effective and well-tolerated in this study, supporting its clinical use in pretreated HER2-positive MBC patients in China. ClinicalTrials.gov Identifier: NCT04262804.

Current Options for Second-Line Systemic Therapy in Metastatic Renal Cell Carcinoma.

Standard systemic therapy of advanced renal cell carcinoma (RCC) involves targeting angiogenesis, mainly through tyrosine kinase inhibitors (TKI) against the vascular endothelial growth factor receptor (VEGFR) pathway and targeting the immune checkpoints, namely, programmed death-1 (PD-1) or its ligand (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA4). With current strategies of combining these two approaches in the front-line setting, less is known about optimal selection of therapy upon development of resistance in the second and later lines of treatment for progressive disease. This review discusses currently available therapeutic options in patients who have progressive RCC after prior treatment with double immune check-point inhibitors (ICIs) or ICI-TKI combinations.

Impact of gender on response to immune checkpoint inhibitors in patients with non-small cell lung cancer undergoing second- or later-line treatment.

BackgroundSeveral previous clinical trials have reported that male patients with non-small cell lung cancer (NSCLC) respond better to immunotherapy than females. However, the impact of gender on prognosis remains uncertain because no real-world study considering various factors that affect patients’ response to immunotherapy with gender exists. Therefore, we evaluated the effect of gender on immunotherapy response adjusted by multiple factors in actual clinical practice.MethodsThis study was a single-center real-world retrospective cohort study, comprising 387 patients with NSCLC who received pembrolizumab, nivolumab, or atezolizumab alone as second- or later-line treatments. Subsequently, we compared their progression free survival (PFS) and overall survival (OS) scores based on gender, then analyzed prognostic factors accounting for immunotherapy response.ResultsThe mean age of the understudied patients was 64.0 years old, comprising 68.7% males, with non-squamous cell carcinoma accounting for 70.3% of these patients. Male patients also showed higher smoking rates, programmed death-ligand 1 (PD-L1) expression, and expression of wild type epidermal growth factor receptor (EGFR), known as favorable prognostic factors. However, no difference in PFS and OS according to gender was observed [PFS 2.2 (male) vs. 2.1 (female) months, P=0.144; OS 7.6 (male) vs. 8.8 (female) months, P=0.383]. Furthermore, an Eastern Cooperative Oncology Group (ECOG) performance status ≥2, high expression of PD-L1, and EGFR mutations were proposed as prognostic factors in multivariate analysis for PFS. Besides, ECOG performance status ≥2 and squamous cell carcinoma were poor prognostic factors accounting for OS. Yet, gender was not an independent prognostic factor in PFS and OS.ConclusionsGender was not an independent prognostic factor for immunotherapy in real-world data although various factors affected immunotherapy response, such as wild type EGFR and high expression of PD-L1, which frequently occur in males.

Real-world overall survival of patients receiving cetuximab in later lines of treatment for metastatic colorectal cancer.

Aim: To examine characteristics of and treatment duration and real-world overall survival (rwOS) in patients receiving cetuximab as second-line (2L) or third-line (3L) treatment for metastatic colorectal cancer. Materials & methods: This was a retrospective study of 1096 and 684 patients in 2L and 3L cohorts, respectively. Results: The most common cetuximab-based regimens were cetuximab+ folinic acid, fluorouracil and irinotecan (2L: 44%; 3L: 32%) and cetuximab+irinotecan (2L: 28%; 3L: 35%). Kaplan-Meier survival estimates and stepwise Cox regression model analysis demonstrated mediantreatment duration and rwOS of 3.7 and 14.4 months, respectively, in patients receiving treatment in the 2L cohort. In the 3L cohort, treatment duration was 3.3 months and rwOS was 12.0 months. Conclusion: This large real-world study provides evidence of rwOS in patients with metastatic colorectal cancer receiving cetuximab-based regimens as 2L or 3L treatment.

1255P da VINci: Safety and efficacy of the OTSGC-A24 vaccine and nivolumab in metastatic gastric cancer

Novel combination immune-oncology strategies aim to improve efficacy while maintaining low toxicity levels. In metastatic gastric cancer (GC), the efficacy of single agent immunotherapy in later lines of treatment is modest. OTSGC-A24 is a cocktail of peptide vaccines against GC specific antigens which induces cytotoxic T lymphocyte (CTL) activity and modulates the intra-tumoral immune contexture. We hypothesize that the combination of OTSGC-A24 and immunotherapy will improve response rates while maintaining low toxicities. da VINci is a phase Ib study combining OTSGC-A24 (SC 1mg Q2W) with nivolumab (IV 240mg Q2W) in HLA A*24:02 subtype patients with GC who progressed on ≥1 line of chemotherapy. Patients were immunotherapy naïve. The primary objective was to evaluate safety and dose limiting toxicities (DLT); secondary objectives included response rate (RECIST v1.1) and survival. Serial tumor biopsies were performed prior to treatment, after 4 weeks of the combination, and at progression. Sixty-eight patients were pre-screened from February 2019 to November 2021, 25 (36.8%) were eligible. Of these, 18 have commenced on treatment. No DLTs were observed. Most frequent all grade toxicities were injection site reactions (n=5 [27.8%], ≥G3=0), fatigue (n=5 27.8%], ≥G3=0), rash (n=5 [27.8%], ≥G3=1), transaminitis (n=3 [16.7%], ≥G3=0), fever (n=3 [16.7%], ≥G3=0). Three patients (16.7%) had partial response (PR), 6 patients (33.3%) had stable disease (SD) while 9 patients (50%) had progressive disease. The median progression-free survival (PFS) was 1.7 months (range 0.4 – 24.2) with a 6-month PFS rate of 27.8% (n=5). The median overall survival (OS) was 3.6 months (range 4.6 – 30.9). Of note, durable clinical benefits were observed in those with SD or PR where the median PFS was 13.1 months (range 2.5 – 24.2) and median OS was 18.6 months (range 2.5 – 30.9). OTSGC-A24 in combination with nivolumab was well tolerated without any unexpected safety signals. The combination showed promising anti-tumor activity with meaningful durable disease control in metastatic GC patients previously treated with chemotherapy. These results support further investigation in randomized studies. Translational studies are underway.

446TiP Randomized phase III study of bi-weekly trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) vs. FTD/TPI for chemorefractory metastatic colorectal cancer (mCRC): ROBiTS/JCOG2014

FTD/TPI is widely used as a late-line treatment for patients with mCRC who are refractory or intolerant to standard chemotherapy based on the results of phase III studies RECOURSE (Mayer RJ, N Engl J Med 2015.) and TERRA (Xu J, J Clin Oncol 2018.). More recently, the efficacy of the combination of FTD/TPI and BEV has also been reported, albeit in phase II studies (Kuboki Y, Lancet Oncol 2017. Pfeiffer P. Lancet Oncol 2020.). However, the combination of FTD/TPI and BEV increased the frequency of neutropenia, a dose-limiting toxicity of FTD/TPI, with Grade 3 or higher reported as 44%-72%.

1119P Real-world efficacy and safety of anlotinib in combination with PD-1/PD-L1 inhibitors as first-line or second-line treatment in advanced non-small cell lung cancer

Antiangiogenic therapy combined with PD-1/PD-L1 inhibitors has shown excellent efficacy in advanced NSCLC pts. The ALTER 0303 trial showed that anlotinib improved both PFS and OS in later-line treatment for advanced NSCLC. The purpose of this study is to investigate the efficacy and safety of anlotinib in combination with PD-1/PD-L1 inhibitors as first-line or second-line treatment in advanced non-small cell lung cancer in the real-world setting. This is a prospective, multicenter real-world study. The NSCLC cancer patients who received anlotinib in combination with PD-1/PD-L1 inhibitors in first-line or second-line were enrolled. The primary endpoint was PFS (progression-free survival), and secondary endpoints were ORR (objective response rate), DCR (disease control rate) and OS (overall survival). The response to treatment was evaluated according to RECIST version 1.1. In addition, adverse events were evaluated by CTCAE v5.0. From Aug 2021 to Apr 2022, 69 patients were enrolled in fifteen centers and 23 of them have received at least one tumor assessment. Median age was 66 (range:39-79); 78.3% male, 4.3% brain metastasis, 91.3% ECOG PS 1. 10 (43.5%) and 13 (56.5%) patients received anlotinib combined with PD-1 inhibitors as first-line and second-line therapy, respectively. Among all patients, 6 patients were partial response (PR), 15 patients were stable disease (SD), illustrating ORR of 26.1% and DCR of 91.3%. In the first-line, ORR was 20%, DCR was 90%. In the second-line, ORR was 30.8%, DCR was % 92.3. Median PFS was 7.70 months (95%Cl: 4.49, 10.91) and median OS was not reached. The most common Grade 3-4 AEs were neutropenia 4.34%, thrombocytopenia 4.34%, leukopenia 4.34%, hand-foot syndrome 4.34% and there were no Grade 4/5 toxicities. This real-word study finds that anlotinib combined with PD-1/PD-L1 inhibitors shows good efficacy and safety in NSCLC patients. The treatment effects are similar to the outcomes in comparable clinical trials, which support the further recommendation of anlotinib combined with PD-1 inhibitors in the treatment of NSCLC.

Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab.

In Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy. The clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves. During January 2017-June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70years; male, 77%). With a median follow-up period of 9.1 (range, 1.0-34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0-16.6) and 4.0 (95% CI, 2.6-5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR < 0.62 (hazard ratio, 0.39; 95% CI, 0.22-0.67; p = 0.001). Inflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR < 0.62, suggesting that CAR adequately reflects prognosis.

Real-life analysis of treatment approaches and the role of inflammatory markers on survival in patients with advanced biliary tract cancer

Objectives Advanced stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients. Methods A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed. Results At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51–6.82), and the median overall-survival (OS) time was 16.8 months (95% CI: 13.9–19.6). Treatment choice (p < 0.001 HR:0.70 CI95% 0.55-0.9), performance status (p < 0.001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = 0.02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < 0.001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < 0.001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = 0.002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < 0.001 HR:0.55 CI 95% 0.38-0.79; p = 0.007 HR:0.51 CI95% 0.31-0.83, respectively). Conclusion SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions.

Mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma.

Follicular lymphoma has a chronic clinical course with an overall survival of 80% at 10 years, justifying its classification as an indolent B-cell lymphoma. 1 Batlevi CL Sha F Alperovich A et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020; 10: 74 Google Scholar Unfortunately, follicular lymphoma is a heterogenous disease, and about one in five patients relapses within 2 years after the start of initial treatment. 2 Casulo C Byrtek M Dawson KL et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare study. J Clin Oncol. 2015; 33: 2516-2522 Google Scholar Furthermore, retrospective data have shown that progression-free survival and overall survival substantially decrease in the relapsed setting, reflecting the clinical experience that patients with follicular lymphoma become more treatment-resistant in later lines of therapy. 1 Batlevi CL Sha F Alperovich A et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020; 10: 74 Google Scholar Thus, despite the generally indolent nature of follicular lymphoma, a great unmet medical need exists for efficient treatments for patients with relapsed or refractory follicular lymphoma, and the therapeutic armamentarium for later lines of treatment is particularly scarce. Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 studyFixed-duration mosunetuzumab has a favourable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory follicular lymphoma and two or more previous therapies. Full-Text PDF

Prospective Cohort Study of Palbociclib Treatment in Postmenopausal Patients With Unresectable and Metastatic Hormone Receptor-Positive Breast Cancer: Study Protocol for a CSPOR-BC Palbociclib Cohort Trial.

BackgroundCombining palbociclib with letrozole or fulvestrant improved progression-free survival in hormone receptor (HR)-positive and human epidermal growth factor receptor-negative metastatic breast cancer. However, combining palbociclib to endocrine treatment increases toxicity and cost compared with the endocrine treatment alone. Moreover, palbociclib treatment may affect the outcome of the subsequent treatment because its benefit in terms of overall survival has not been observed yet. Therefore, it is crucial to examine whether palbociclib can improve clinical outcomes and quality of life (QoL) of patients in the real world.MethodsA prospective observational study with palbociclib is planned in 3 cohorts (A, B, and C) as per the line of endocrine treatment (i.e., first-line, second-line, or third-line or later-line treatment) for postmenopausal metastatic or unresectable breast cancer. The primary endpoint is progression-free survival in each treatment line, the most commonly used endpoint for global phase 3 studies. As per the results of these studies, the planned sample size is 700 cases: cohort A, 340 cases; cohort B, 200 cases; and cohort C, 130 cases. The secondary endpoints are overall survival, clinical benefit rate, time to chemotherapy, adverse events (AEs), patient-reported outcomes (PROs), and health-related QoL (HRQoL). These endpoints are evaluated again during the subsequent treatment. This study will examine whether the efficacy, safety, and QoL effects of palbociclib treatment in daily clinical practice are not inferior compared to those in clinical trials and whether palbociclib treatment affects the efficacy and safety of the subsequent treatment. Moreover, this study would provide information on the most effective time of adding palbociclib to endocrine treatment.DiscussionThe reproducibility of randomized clinical trials (RCTs) using real-world data must be confirmed to evaluate whether real-world treatment benefits are similar to those observed in RCTs. Although the efficacy of palbociclib has been confirmed in RCTs, Aes of this drug, including its toxicities and cost, are not comparable to those of mono-hormone therapies. Thus, PROs/HRQoL is an important element of this study because several patients with HR-positive metastatic breast cancer have diseases for which sequential hormone therapy is preferential.

Esophagogastric Cancers: Integrating Immunotherapy Therapy Into Current Practice.

Immunotherapy (IO) agents have led to significant improvements in patient outcomes across many tumor types. There have been great efforts to introduce immune checkpoint inhibitors into the treatment paradigm of esophagogastric cancers as well. A number of randomized phase III trials, which will be reviewed here, established the role of these agents in both early-stage and advanced-stage disease. Adjuvant nivolumab is US Food and Drug Administration-approved after neoadjuvant chemoradiation and resection of esophageal and gastroesophageal junction cancers on the basis of the phase III CheckMate 577 trial. In the advanced setting, patients with programmed death receptor ligand-1-positive tumors should be recommended IO in combination with chemotherapy in the first-line setting on the basis of the results from KEYNOTE 590, CheckMate 649, and CheckMate 648. Across trials, chemotherapy continues to play a critical role in the first-line setting and should be offered to all patients who are eligible for systemic therapy, including those with biomarker select tumors. In the later lines of treatment, IO has modest activity, and prior studies have grown largely irrelevant because of the enrollment of IO-naive patients. Similar to other disease types, patients with microsatellite unstable (microsatellite instability high) tumors represent a unique cohort that is more sensitive to IO. However, there are no randomized studies evaluating how best to apply IO in early or advanced stages specifically for the treatment of patients with microsatellite instability high upper GI tumors. Questions remain how to best select patients who benefit from IO treatments, how to augment IO activity in programmed death receptor ligand-1-negative tumors, and how to incorporate IO in late-line settings or for recurrent disease that has been treated with IO-containing regimens during early stages.

Physician treatment preferences for relapsed/refractory multiple myeloma: a discrete choice experiment.

Aim: This study aimed to assess physician preferences for later lines (third to fifth) of therapy in patients with relapsed/refractory multiple myeloma (RRMM) in the USA. Materials & methods: Factors relevant to physicians' treatment preferences for RRMM were identified from a literature search and refined in a qualitative phase. Preferences were quantitatively assessed using a discrete choice experiment. Physicians (n=227) made choices regarding treatment scenarios for RRMM. Results: Efficacy had the highest mean relative importance, with overall survival valued as most important when making treatment decisions for patients with RRMM. Reduced incidences of keratopathy and thrombocytopenia had similar relative importance in later-line treatment. Conclusion: Greater understanding of physicians' criteria for clinical decision-making may help inform wider adoption of new treatments.

CO107 Progression-Free Survival in Patients with Advanced or Metastatic, Hormone Receptor Positive, HER2-Negative Breast Cancer Treated with Palbociclib in Combination with Fulvestrant: A Real-World Study

To evaluate progression free survival (PFS) in patients with advanced or metastatic, hormone receptor positive (HR+), HER2-negative (HER2-) breast cancer treated with palbociclib in combination with fulvestrant as second or later lines of treatment.

EE370 Assessing the Impact of Crossover Adjustment on the Cost-Effectiveness (CE) of Nivolumab Versus Everolimus in Pre-Treated Advanced Renal Cell Carcinoma (ARCC) in the United States (US)

In clinical trials, crossover from assigned control treatments onto other experimental treatments or alternatives often creates difficulties in estimating the underlying comparative efficacy and CE of experimental treatments. We examined the impact of adjusting crossover from everolimus to nivolumab in the third- or later-line treatment in the phase III CheckMate 025 trial on the estimated relative efficacy and CE of nivolumab in pre-treated patients with aRCC.

CO53 Comparison of Real-World Later-Line Treatment Outcomes in Patients with Microsatellite-Instability High (MSI-H) Versus Microsatellite-Stable (MSS) Metastatic Colorectal Cancer (mCRC) in the United States (US)

Evidence suggests that patients with MSI-H or mismatch repair deficient (dMMR) mCRC have worse outcomes than those with MSS or mismatch repair proficient (pMMR) mCRC, but this mostly relates to first-line (1L) treatment. We compared time to next treatment or death (TTNTd) and overall survival (OS) in patients in the US with MSI-H/dMMR vs MSS/pMMR tumors on second-line (2L) and third-line (3L) non-immunotherapy standard of care mCRC treatment.

Healthcare Resource Utilization and Cost of Patients with Multiple Myeloma in Germany: A Retrospective Claims Data Analysis.

ObjectiveThis study aimed to analyze the healthcare resource use (HCRU) and associated costs of multiple myeloma (MM) using German claims data.MethodsAnonymized claims data from one of the largest sickness funds in Germany were analyzed. Costs and HCRU were calculated from the perspective of the statutory health insurance. To analyze MM-associated incremental costs in a most recent calendar period for an overall MM population (31 March 2018–31 March 2019), a prevalent cohort of MM patients (continuously insured during 01 January 2010 until 31 March 2019 or death; two or more outpatient and/or one inpatient MM diagnoses [ICD-10: C90.0-] and alive on 31 March 2018) was compared with a control group (not diagnosed with MM) employing propensity-score matching. Additionally, to describe MM-associated HCRU and costs for treated patients per line of treatment (lot), a cohort of newly treated patients was considered (≥ 12 months’ pre-index period without MM treatment). Therapy lines were determined based on observed days of medication supply, treatment switches, and treatment discontinuations.ResultsOverall, 2523 prevalent MM patients (52.0% female, mean age: 71.3 years) and 1673 newly treated MM patients (50.2% female, mean age: 73.0 years) met the selection criteria and were included in the analyses. After matching, a non-MM counterpart could be identified for 2474 prevalent out of 2523 MM patients. MM-associated incremental HCRU was characterized by an increased number of hospitalizations and a higher number of outpatient specialist visits (per patient-year [ppy] 0.48 additional hospitalizations and 3.80 additional specialist visits; p < 0.001), being also drivers of the associated total incremental add-on costs (15,381.09 € ppy, p < 0.001). Among newly treated patients, total direct costs ppy increased as patients received subsequent treatments (1st lot: 67,681,55 €; 4th lot+: 114,934.01 €), driven by outpatient MM prescriptions (1st lot: 28,692.32 €; 4th lot+: 62,980.72 €).ConclusionThe economic burden of MM is driven by outpatient prescriptions, inpatient hospitalizations, and outpatient specialist visits. Treatment and overall costs increase substantially when patients move to later lines of treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00344-4.