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Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents. Objectives: We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics. Design: This is a retrospective real-world cohort study of BRAF V600E mutated mCRC patients treated with second-line EC ± B at 20 Italian centres. Methods: Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients. Results: A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases (p = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR)DpR⩾30%: 0.52, 95% CI: 0.30–0.90, p = 0.02) and median cut-off values (HRDpR⩾15%: 0.55, 95% CI: 0.33–0.92, p = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78–0.98, p = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR (p DpR⩾30% = 0.04; p DpR⩾15% = 0.04; p cont. = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected. Conclusion: A DpR of at least 15% independently predicts PFS benefit in BRAF V600E mutated mCRC patients treated with second-line EC ± B. [ABSTRACT FROM AUTHOR]

Summary: The association between depth of response (DpR) and treatment outcomes has been documented across various types of cancer. Immune checkpoint inhibitor (ICI)-based treatment is globally used as first-line treatment for non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) expression ≥ 50%. However, in this population, the significance of DpR is not elucidated. Patients with advanced NSCLC and PD-L1 expression ≥ 50% who received ICI-monotherapy or ICI plus chemotherapy were retrospectively enrolled into this study. Treatment responses were grouped into DpR 'quartiles' by percentage of maximal tumor reduction (Q1 = 1–25%, Q2 = 26–50%, Q3 = 51–75%, and Q4 = ≥ 76%), and no tumor reduction (NTR). The association between DpR and survival rates were determined using hazard ratios (HR) generated by the Cox proportional hazards model. The Kaplan–Meier method was used to determine survival outcomes. A total of 349 patients were included, of which 214 and 135 patients received pembrolizumab monotherapy and ICI plus chemotherapy, respectively, as first-line treatments. The majority of the patients were male. All DpR quartiles, especially Q4, showed an association with progression-free survival (PFS)/overall survival (OS). In the Q4 cohort, patients who received pembrolizumab had a longer PFS than those who received ICI plus chemotherapy. High DpR was associated with longer PFS and OS, with a more pronounced effect observed with pembrolizumab monotherapy than with ICI plus chemotherapy. [ABSTRACT FROM AUTHOR]

\nIntroduction: Nivolumab plus ipilimumab combination therapy has been administered as a first-line treatment in Japan since 2022 for patients with unresectable progressive or recurrent esophageal cancer. The efficacy and safety of this immune checkpoint inhibitor (ICI) doublet therapy are now being evaluated, and it is necessary to identify populations that benefit from this treatment at an early phase after initiation. For patients not showing early benefit, changing as soon as possible to other therapeutic strategies could improve their survival outcomes. Therefore, we attempted to identify decision-making factors such as early tumor shrinkage (ETS) based on treatment experience with ICI doublet therapy. Methods: The study included 19 patients who received nivolumab plus ipilimumab for non-surgically indicated or recurrent esophageal cancer between July 2022 and November 2023. Tumors were assessed approximately every 2 months after treatment initiation. The effects of ETS, depth of response (DpR), and clinicopathologic features, including immune-related adverse events (irAEs), on progression-free and overall survival were evaluated using Kaplan-Meier plots and Cox proportional hazard models. Results: The mean duration of ICI doublet administration was 5.89 months (range, 1–16 months). At first evaluation, patients who exhibited no tumor progression >20% indicated possible response to ICI doublet therapy, and patients whose tumors shrank even minimally exhibited favorable progression-free survival. Higher DpR at any cut-off line exhibited better progression-free survival than those with lower DpR. Fifteen patients experienced irAEs, with 13 of these patients experiencing irAEs within 3 months of treatment initiation. irAEs were associated with the efficacy of ICI doublet therapy, but efficacy could not be predicted based on early irAE experience. Conclusion: ETS-high, DpR-high, and irAEs might be associated with favorable responses to nivolumab plus ipilimumab. As a predictor of efficacy at an early phase, ETS >0% could be a deciding factor for continuing ICI doublet therapy. We studied the usefulness of evaluating early tumor shrinkage (ETS) as an efficacy predictor in patients with inoperable or recurrent esophageal cancer treated with nivolumab plus ipilimumab therapy. The immune checkpoint inhibitor (ICI) doublet therapy has been administered since 2022, and there are still not many patients who received this treatment all over the world. It is necessary to find well-responders to this treatment as soon as possible to improve outcomes and consider therapeutic strategies. We analyzed tumor shrinkage and clinicopathologic features in patients with inoperable or recurrent esophageal cancer treated with the treatment. ETS was defined as the percent decrease in the sum of the largest diameter of the target lesions at first evaluation after treatment initiation compared to that at baseline. Regarding ETS, those whose tumors shrank even minimally had favorable progression-free survival. Immune-related adverse events were also associated with the sensitivity and efficacy of ICI doublet therapy, but to find the efficacy at an early phase, ETS could be a decision-making factor for predicting the efficacy and continuation of ICI doublet therapy. [ABSTRACT FROM AUTHOR]

Introduction: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. Methods: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. Results: Twenty-seven patients (51%) were treatment naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. Conclusion: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the safety and efficacy of first-line nivolumab plus chemotherapy for real-world patients with human epidermal growth factor receptor 2 (HER2)-negative advanced gastric cancer (AGC). Materials and methods: This single-institutional retrospective study enrolled patients with HER2-negative AGC who were treated with nivolumab plus chemotherapy between September 2021 and January 2024. Early tumor shrinkage (ETS) and depth of response (DpR) were assessed. Results: There were 136 patients with a median age of 65 years (range 27-83 years); 57% were men, the rate of programmed cell death ligand 1 combined positive score of

Abstract Deeper responses are associated with longer survival in multiple myeloma (MM); however, limited data exist on the impact of response kinetics on outcomes. We investigated progression‐free survival (PFS) and duration of response (DOR) by response depth and in early (best confirmed response 0–4 months; n = 424) versus late responders (best confirmed response >4 months; n = 281). Newly diagnosed patients enrolled in TOURMALINE‐MM2 receiving ixazomib‐lenalidomide‐dexamethasone (IRd) (n = 351) or placebo‐Rd (n = 354) were evaluated post hoc. Deeper responses were associated with longer PFS (complete response [CR] not reached [NR], very good partial response [VGPR] 37.2 months, partial response [PR] 16.4 months) and DOR (CR NR, VGPR 42.6 months, PR 15.4 months). Among patients with a PFS (n = 511) or DOR (n = 484) of ≥6 months who achieved ≥PR, median PFS was prolonged among late versus early responders receiving IRd (59.7 vs. 17.9 months) or placebo‐Rd (56.6 vs. 12.4 months), as was median DOR (IRd, NR vs. 20.9 months; placebo‐Rd, 58.2 vs. 11.7 months). While the treatment paradigm for newly diagnosed MM is treatment to progression, our findings suggest slowness of response to a proteasome inhibitor‐immunomodulatory drug‐steroid combination is not a negative predictor of outcome.

Background: Pembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear. Methods: This study included 66 patients with R/M HNSCC who received a pemblolizumab-containing regimen as a first-line therapy at Tohoku University Hospital, Sendai, Japan. The patients’ characteristics, combined positive score, baseline tumor size, tumor response, DpR, overall survival (OS), progression-free survival (PFS), PFS2, and adverse events were reviewed. The associations between DpR and survival outcomes were analyzed. Results: The 1 year-OS and 1 year-PFS rates of pembrolizumab-containing regimens were 69.4% and 24.4%, respectively. The response rate was 28.8%. The mean and median values of tumor change from baseline were 5.1% and −9.0%. In the correlation analysis, a significant negative correlation was observed between tumor change rate from baseline and survival outcomes (OS: r= −0.41, p=0.0017; PFS: r=−0.49, p<0.001). In the multivariate analysis, DpR with tumor change of ≤−45 was associated with better OS and PFS. Conclusion: DpR induced by pembrolizumab-containing regimens may be a predictive factor for OS and PFS in patients with R/M HNSCC. [ABSTRACT FROM AUTHOR]

Objective To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response. [ABSTRACT FROM AUTHOR]

Background: We herein investigated the association between early tumor shrinkage (ETS) and depth of response (DpR) and clinical outcomes in patients with metastatic esophageal cancer treated with 2-weekly docetaxel combined with cisplatin plus fluorouracil (bDCF) using data from the JCOG0807, a phase I/II trial of bDCF as first-line chemotherapy for metastatic esophageal cancer. Methods: ETS was defined as a percent decrease in the sum of the target lesions' longest diameter after 8 weeks, whereas DpR was defined as a percentage of the maximal tumor shrinkage during the treatment course. Multivariable analyses were conducted to identify significant prognostic variables in progression-free survival (PFS) and overall survival (OS): one for ETS and covariates, and another for DpR and covariates. Results: Among 53 patients, 35 patients with ETS ≥ 20% (66.0%) had longer PFS (7.5 vs. 3.4 months, hazard ratio [HR]: 0.26, 95% confidence interval [95% CI] 0.14–0.49), OS (13.8 vs. 6.1 months, HR 0.20, 95% CI 0.11–0.39), and PPS (6.4 vs. 2.8 months, HR 0.38, 95% CI 0.20–0.72) than those with ETS < 20%. In addition, 37 patients with DpR ≥ 30% (69.8%) had longer PFS (7.5 vs. 2.9 months, HR 0.17, 95% CI 0.08–0.34), OS (13.8 vs. 6.0 months, HR 0.14, 95% CI 0.07–0.27), and PPS (6.8 vs. 2.8 months, HR 0.30, 95% CI 0.15–0.58) than those with DpR < 30%. Multivariable analyses revealed that each ETS and DpR was an independent factor of longer PFS and OS. Conclusions: ETS and DpR might be associated with clinical outcomes in patients with metastatic esophageal cancer treated with bDCF. [ABSTRACT FROM AUTHOR]

In patients with RAS wild-type metastatic colorectal cancer, depth of response (DpR) has gained importance as a novel end-point in clinical trials. We investigated the overall DpR, as well as the prognostic and predictive impact of DpR to induction therapy (six cycles of 5-fluorouracil, leucovorin [FU/FA], oxaliplatin [FOLFOX] and panitumumab [Pmab]) on consecutive maintenance therapy (FU/FA plus Pmab or FU/FA alone) in patients treated within the PanaMa trial. Central radiological assessment was performed according to RECIST 1.1. DpR was defined as percentage change in tumour diameter within defined time intervals (induction therapy, maintenance therapy, total course of therapy). For prognostic and predictive analyses, median DpR (

Introduction/Background Lebrikizumab (LEB) is a novel monoclonal antibody that binds with high affinity and slow off-rate to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967) are identically designed Phase 3 trials that evaluated LEB as a monotherapy treatment for moderate-to-severe atopic dermatitis (AD). Many patients who met the protocol-defined response criteria at Week 16, defined as achieving ≥75% improvement in the Eczema Area and Severity Index (EASI 75) or an Investigator's Global Assessment of 0 or 1 (IGA 0/1) without use of rescue therapy, maintained a deep response up to Week 521. Deep response was defined as maintaining an IGA 0 (clear skin), a 100% improvement in the Eczema Area and Severity Index (EASI 100), or a Pruritus Numeric Rating Scale score of 0 or 1 (Pruritus NRS 0/1). Patients completing Week 52 were given the option to roll over into a long-term extension (LTE) study, ADjoin (NCT04392154), allowing the opportunity to analyze deep response for a longer period of time. This analysis supports the evolution of AD treatment goals toward maintaining higher efficacy thresholds for a longer duration. Objectives To present the long-term maintenance of LEB's depth of response for up to 104 weeks of treatment (52 weeks in the ADvocate studies and 52 weeks in the ADjoin study). Methods Patients entering ADjoin from ADvocate1 and ADvocate2 continued taking the same LEB dose as the parent study. Patients receiving placebo (LEB withdrawal) during the maintenance period of ADvocate1 and ADvocate2 transitioned to receive LEB every 2 weeks (Q2W) during ADjoin (data not included in this analysis). The proportion of patients achieving IGA and EASI responses were calculated from the LEB-treated patients who were IGA 0/1 or EASI 75 responders, respectively, at Week 16 in ADvocate1 and ADvocate2. The proportion of patients achieving a Pruritus NRS 0/1 response were calculated from the LEB patients who were per protocol responders at Week 16 of ADvocate1 and ADvocate2. Each patient's absolute Pruritus NRS score was calculated by averaging daily scores from the previous seven days with at least one nonmissing value. The weekly score was then rounded to the nearest integer. Consistent with common reporting practices for LTE studies, this post hoc analysis reports observed data which were analyzed regardless of rescue medication use or treatment discontinuation. Results From Week 52 to Week 104, the proportion of IGA 0 responders was maintained and slightly increased in patients treated with LEB Q2W (50.8% [N=59] to 52.3% [N=44]) and LEB every 4 weeks (Q4W; 43.5% [N=69] to 45.5% [N=55]). Greater improvements over the second year of treatment were seen in the proportion of EASI 100 responders treated with LEB Q2W (36.4% [N=88] to 39.7% [N=68]) and LEB Q4W (30.7% [N=101] to 41.3% [N=80]) as well as the proportion of Pruritus NRS 0/1 responders treated with LEB Q2W (46.3% [N=80] to 57.4% [N=61]) and Q4W (47.9% [N=94] to 55.4% [N=65]). Although rescue medication was allowed during ADjoin, a relatively low proportion of patients received ≥1 topical rescue medication in the LEB Q2W (9.8%) and LEB Q4W (15.2%) treatment arms. Conclusions These 2-year results demonstrate an extended maintenance of deep response in patients treated with LEB Q2W and LEB Q4W after responding to 16 weeks of LEB Q2W. Approximately 50% and 40% of LEB-treated patients sustained total skin clearance (IGA 0 and EASI 100, respectively) and more than 55% of LEB-treated patients reported no or minimal itch (Pruritus NRS 0/1). Maintenance treatment with LEB Q2W and LEB Q4W allows patients and providers to elevate their expected treatment goals in AD beyond EASI 75 and IGA 0/1 response. [ABSTRACT FROM AUTHOR]

IntroductionEarly tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial.MethodsDpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex.ResultsIn 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS/BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p < 0.001; OS: p = 0.012) and molecular subgroup (PFS: p < 0.001; OS: p < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p < 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965).ConclusionsInitial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population.

Introduction: Early tumor shrinkage (ETS), depth of response (DpR), and time to DpR represent exploratory endpoints that may serve as early efficacy parameters and predictors of long-term outcome in metastatic colorectal cancer (mCRC). We analyzed these endpoints in mCRC patients treated with first-line bevacizumab-based sequential (initial fluoropyrimidines) versus combination (initial fluoropyrimidines plus irinotecan) chemotherapy within the phase 3 XELAVIRI trial. Methods: DpR (change from baseline to smallest tumor diameter), ETS (≥20% reduction in tumor diameter at first reassessment), and time to DpR (study randomization to DpR image) were analyzed. We evaluated progression-free survival and overall survival with ETS as stratification parameter according to treatment arm, molecular subgroup, and sex. Results: In 370 patients analyzed, a higher rate of ETS (60.9% vs. 43.5%; p = 0.001) and significantly greater DpR (-40.0% vs. -24.7%; p < 0.001) were observed in the initial combination therapy arm. The improvement was pronounced in RAS / BRAF wild-type tumors. ETS correlated with improved survival irrespective of treatment arm (PFS: p < 0.001; OS: p = 0.012) and molecular subgroup (PFS: p < 0.001; OS: p < 0.001). Male patients in contrast to female patients with ETS had survival benefit (PFS: p < 0.001, HR 0.532; OS: p < 0.001, HR 0.574 vs. PFS: p = 0.107; OS: p = 0.965). Conclusions: Initial irinotecan-based combination therapy with bevacizumab improved ETS and DpR in mCRC patients with a particularly high irinotecan sensitivity of RAS/BRAF wild-type tumors. ETS seems to be a suitable prognostic marker for fluoropyrimidine- and bevacizumab-based combinations in mCRC. This finding was rather driven by male patients, potentially indicating that ETS might be less predictive of long-term outcome in an elderly, female population. [ABSTRACT FROM AUTHOR]

Background: The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival., Objective: To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups., Design, Setting, and Participants: CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC., Intervention: Patients were randomized 1:1:1 to lenvatinib 20 mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment., Outcome Measurements and Statistical Analysis: Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1., Results and Limitations: Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or >75% target-lesion reduction by 6 mo had a 24-mo OS probability of ≥91.7%. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4% vs 28.8%) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified., Conclusions: Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS., Patient Summary: In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a "complete response" or had their tumors shrunk by >75% within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients., Patients and Methods: Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate., Results: There was a trend for lower discontinuation rate (45.7% vs. 68.6%, P = .052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P = .035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P = .225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P = .024). There was significantly longer PFS (24.3 vs. 9.1 months, P = .012) and a trend for longer OS (22.4 vs. 61.3 months, P = .061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P = .941) and OS were similar in both groups., Conclusion: Higher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)