Association of Cabozantinib Dose Reductions for Toxicity With Clinical Effectiveness in Metastatic Renal Cell Carcinoma (mRCC): Results From the Canadian Kidney Cancer Information System (CKCis).

BACKGROUND: Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI), has demonstrated efficacy in metastatic renal cell carcinoma (mRCC). The association between toxicity and therapeutic effectiveness has been established with other TKIs. We investigated whether cabozantinib dose reductions, a surrogate for toxicity and adequate drug exposure, were associated with improved clinical outcomes in mRCC. METHODS: Employing the CKCis database, we analyzed patients treated with cabozantinib in the second line or later between 2011 to 2021. The cohort was stratified into those needing dose reductions (DR) during treatment and those not (no-DR). Outcomes, including objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS), were compared based on dose reduction status. The influence of the initial dose on outcomes was also explored. RESULTS: Among 319 cabozantinib-treated patients, 48.3% underwent dose reductions. Response rates exhibited no significant difference between the DR and no-DR groups (15.1% vs. 18.2%, P = .55). Patients with DR had superior median OS (26.15 vs. 15.47 months, P = .019) and TTF (12.74 vs. 6.44 months, P = .022) compared to no-DR patients. These differences retained significance following adjustment for IMDC risk group (OS HR = 0.67, P = .032; TTF HR = 0.65, P = .008). There was no association between the initial dose and ORR, OS, or TTF. CONCLUSION: This study highlights the link between cabozantinib dose reductions due to toxicity and improved survival and time to treatment failure in mRCC patients. These findings underscore the potential of using on-treatment toxicity as an indicator of adequate drug exposure to individualize dosing and optimize treatment effectiveness. Larger studies are warranted to validate these results and develop individualized strategies for cabozantinib when given alone or in combination with immunotherapy.

Population Survival Kinetics Derived from Clinical Trials of Potentially Curable Lung Cancers.

Using digitized data from progression-free survival (PFS) and overall survival Kaplan-Meier curves, one can assess population survival kinetics through exponential decay nonlinear regression analyses. To demonstrate their utility, we analyzed PFS curves from published curative-intent trials of non-small cell lung cancer (NSCLC) adjuvant chemotherapy, adjuvant osimertinib in resected EGFR-mutant NSCLC (ADAURA trial), chemoradiotherapy for inoperable NSCLC, and limited small cell lung cancer (SCLC). These analyses permit assessment of log-linear curve shape and estimation of the proportion of patients cured, PFS half-lives for subpopulations destined to eventually relapse, and probability of eventual relapse in patients remaining progression-free at different time points. The proportion of patients potentially cured was 41% for adjuvant controls, 58% with adjuvant chemotherapy, 17% for ADAURA controls, not assessable with adjuvant osimertinib, 15% with chemoradiotherapy, and 12% for SCLC. Median PFS half-life for relapsing subpopulations was 11.9 months for adjuvant controls, 17.4 months with adjuvant chemotherapy, 24.4 months for ADAURA controls, not assessable with osimertinib, 9.3 months with chemoradiotherapy, and 10.7 months for SCLC. For those remaining relapse-free at 2 and 5 years, the cure probability was 74%/96% for adjuvant controls, 77%/93% with adjuvant chemotherapy, 51%/94% with chemoradiation, and 39%/87% with limited SCLC. Relatively easy population kinetic analyses add useful information.

Trends of Utilization of Systemic Therapies for Metastatic Renal Cell Carcinoma in the Canadian Health Care System.

PURPOSE: Standard-of-care therapies for metastatic renal cell carcinoma (mRCC) have greatly evolved. However, the availability of emerging options in global health care systems can vary. We sought to describe the integration and usage of systemic therapies for mRCC in Canada since 2011. METHODS: We included patients with mRCC enrolled in the Canadian Kidney Cancer Information System, a prospective cohort of patients from 14 Canadian academic centers, who received systemic therapy from January 1, 2011, to December 31, 2021. Patients were stratified by treatment era (cohort 1: 2011-2015, cohort 2: 2016-2021). Stacked bar charts were used to present treatment proportions; Sankey diagrams were used to show the evolution of treatment sequencing between the two cohorts. RESULTS: Four thousand one hundred seven patients were diagnosed with mRCC, of whom 2,752 (67%) received systemic therapy. Among these patients, mean age was 64 years, 74% were male, 75% had clear cell histology, and International Metastatic RCC Database Consortium risk classification was favorable, intermediate, and poor in 16%, 56%, and 28%, respectively. Utilization of immune checkpoint inhibition (ICI)-based treatments has increased in Canada and reflects global and local patterns of approval and adoption. The use of therapies after doublet ICI has mostly shifted toward vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKIs) that were previously used in first line with subsequent treatments reflecting approved and available agents after previous VEGF-TKI. Clinical trial participation among patients who received systemic therapy was 18% in first, 21% in second, and 24% in third line. CONCLUSION: In Canada's publicly funded health care system, availability of standard mRCC therapies broadly reflects access from government-funded clinical trials and compassionate access program sources. In an evolving therapeutic landscape, ongoing advocacy is required to continue to facilitate patient access to efficacious therapies.

What Attributes Matter Most in Physicians? Exploratory Findings from a Single-Centre Survey of Stakeholder Priorities in Cancer Care at a Canadian Academic Cancer Centre.

BACKGROUND: Limited research exists regarding how healthcare stakeholders prioritize the importance of differing physician attributes in oncologists. Identifying these priorities can help ensure that Canadian cancer care continues to meet the needs of its patients. In our previous research, compassion and empathy were identified as important physician attributes, with answers like knowledge, professionalism or communication less common. We hypothesized that respondents may have been assuming other, underlying qualities in their oncologists when they prioritized "compassion" and "empathy". To test this, the current study asks respondents to rank important physician attributes. METHODS: With ethics approval, we asked healthcare stakeholders (physicians, nurses, patients, caregivers, medical students, and allied healthcare providers) to rank the eight most popular qualities or attributes. We identified differences between which characteristics each group valued most in physicians. RESULTS: 375 respondents participated in the survey. "Knowledge" and "competence" were the most popular answers in the current study among all groups except medical students. CONCLUSION: Previously, we identified compassion as a highly valued attribute; however, this survey suggests that this may be with the assumption that a physician is knowledgeable and competent. Future research will use semi-structured interviews to investigate respondents' rationales for making their choices and help interpret our findings in this study.

Outcomes of Second-Line Therapies in Patients With Metastatic de Novo and Treatment-Emergent Neuroendocrine Prostate Cancer: A Multi-Institutional Study.

BACKGROUND: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. PATIENTS AND METHODS: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. RESULTS: Fifty-eight patients (32 de novo NEPC, 26 T-NEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). CONCLUSIONS: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice.

Adjuvant therapy for renal cell carcinoma: 2023 Canadian Kidney Cancer Forum consensus statement.

INTRODUCTION: Several recent randomized trials evaluated the impact of adjuvant immune checkpoint inhibitor (ICI)-based therapy on post-surgical outcomes in renal cell carcinoma (RCC), with disparate results. The objective of this consensus statement is to provide data-driven guidance regarding the use of ICIs after complete resection of clear-cell RCC in a Canadian context. METHODS: An expert panel of genitourinary medical oncologists, urologic oncologists, and radiation oncologists with expertise in RCC management was convened in a dedicated session during the 2022 Canadian Kidney Cancer Forum in Toronto, Canada. Topic statements on the management of patients after surgery for RCC, including counselling, risk stratification, indications for medical oncology referral, appropriate followup, eligibility and management for adjuvant ICIs, as well as treatment options for patients with recurrence who received adjuvant immunotherapy, were discussed. Participants were asked to vote if they agreed or disagreed with each statement. Consensus was achieved if greater than 75% of participants agreed with the topic statement. RESULTS: A total of 22 RCC experts voted on 14 statements. Consensus was achieved on all topic statements. The panel felt patients with clear-cell RCC at increased risk of recurrence after surgery, as per the Keynote-564 group definitions, should be counselled about recurrence risk by a urologist, should be informed about the potential role of adjuvant ICI systemic therapy, and be offered referral to discuss risks and benefits with a medical oncologist. The panel felt that one year of pembrolizumab is currently the only regimen that should be considered if adjuvant therapy is selected. Panelists emphasized current opinions are based on disease-free survival given the available results. Significant uncertainty regarding the benefit and harms of adjuvant therapy remains, primarily due to a lack of consistent benefit observed across similar trials of adjuvant ICI-based therapies and immature overall survival (OS) data. CONCLUSIONS: This consensus document provides guidance from Canadian RCC experts regarding the potential role of ICI-based adjuvant systemic therapy after surgery. This rapidly evolving field requires frequent evidence-based re-evaluation.

A population-based study of factors associated with systemic treatment in advanced prostate cancer decedents.

INTRODUCTION: Life-prolonging therapies (LPTs) are rapidly evolving for the treatment of advanced prostate cancer, although factors associated with real-world uptake are not well characterized. METHODS: In this cohort of prostate-cancer decedents, we analyzed factors associated with LPT access. Population-level databases from Ontario, Canada identified patients 65 years or older with prostate cancer receiving androgen deprivation therapy and who died of prostate cancer between 2013 and 2017. Univariate and multivariable analyses assessed the association between baseline characteristics and receipt of LPT in the 2 years prior to death. RESULTS: Of 3575 patients who died of prostate cancer, 40.4% (n = 1443) received LPT, which comprised abiraterone (66.3%), docetaxel (50.3%), enzalutamide (17.2%), radium-223 (10.0%), and/or cabazitaxel (3.5%). Use of LPT increased by year of death (2013: 22.7%, 2014: 31.8%, 2015: 41.8%, 2016: 49.1%, and 2017: 57.9%, p < 0.0001), driven by uptake of all agents except docetaxel. Adjusted odds of use were higher for patients seen at Regional Cancer Centers (OR: 1.8, 95% CI: 1.5-2.1) and who received prior prostate-directed therapy (OR: 1.3, 95% CI: 1.0-1.5), but lower with advanced age (≥85: OR: 0.54, 95% CI:0.39-0.75), increased chronic conditions (≥6: OR: 0.62, 95% CI: 0.43-0.92), and long-term care residency (OR: 0.38, 95% CI: 0.17-0.89). Income, stage at presentation, and distance to the cancer center were not associated with LPT uptake. CONCLUSION: In this cohort of prostate cancer-decedents, real-world uptake of novel prostate cancer therapies occurred at substantially higher rates for patients receiving care at Regional Cancer Centers, reinforcing the potential benefits for treatment access for patients referred to specialist centers.

A survey of physician perception and practices regarding pharmacological thromboprophylaxis during chemotherapy for bladder cancer.

INTRODUCTION: Patients with advanced bladder cancer receiving chemotherapy have a high risk of venous thromboembolism (VTE); however, we hypothesized these patients were not routinely offered thromboprophylaxis. The objective of this study was to characterize practice patterns and perceptions of Canadian urologic and medical oncologists, and to identify research needs regarding thromboprophylaxis for patients with bladder cancer. METHODS: An online survey was distributed to Canadian urologic and medical oncologists who manage advanced bladder cancer. The survey explored physician opinions regarding VTE rates, risk stratification scores, thromboprophylaxis use in different treatment settings, and interest in clinical trials. RESULTS: Seventy physicians were invited and 36 (51%) completed the survey, including 20 (56%) urologic oncologists and 16 (44%) medical oncologists. Most respondents (35; 97%) believed that exposure to platinum chemotherapy increases VTE risk. For patients receiving neoadjuvant chemotherapy, 34 (94%) respondents estimated the risk of VTE to be 10% or higher, yet 25 (69%) indicated they do not routinely recommend thromboprophylaxis. Physicians frequently (10; 40%) defer the decision to another physician, while eight (32%) believe there is not enough evidence to guide best management. Similar responses were obtained for metastatic patients. Almost all (94%) respondents were interested in participating in a thromboprophylaxis trial for patients with bladder cancer. CONCLUSIONS: Patients with bladder cancer receiving chemotherapy in Canada are not routinely offered thromboprophylaxis. We found strong interest among Canadian oncologists to participate in clinical trials examining this topic.

Adverse Events Associated with Immune Checkpoint Inhibitors: Overview of Systematic Reviews.

BACKGROUND: Recognition and management of adverse events (AEs) associated with immune checkpoint inhibitor (ICI) use by cancer patients requires expertise from multiple disciplines. Greater awareness of potential AEs may result in earlier recognition, appropriate management, and better patient outcomes. OBJECTIVE: The primary objective of this overview of systematic reviews was to synthesize and consolidate systematic review evidence describing the incidence proportion and severity of AEs associated with various ICI therapies across different cancers. METHODS: A systematic literature search of four databases was conducted to identify systematic reviews that describe the incidence proportion and severity of AEs related to ICI therapy in cancer patients. A systematic review was eligible if it included adults with cancer; on ICI alone or in combination with another ICI, chemotherapy, or targeted therapy; severity (graded according to the Common Terminology Criteria for Adverse Events) and incidence proportion of AEs and whether it reported its eligibility criteria. AEs of interest were identified through an iterative ranking exercise by key stakeholders and knowledge users. Extraction of PICOTTS elements and quality indicators (AMSTAR-2) were used to manage overlap of primary studies across systematic reviews at the outcome level. Cancer subtypes were mapped to drug class and AE severity. RESULTS: Overall, 129 systematic reviews met the inclusion criteria for data mapping. Systematic reviews reported incidence proportions for more than 76 AEs, of which 34 were identified as AEs of interest. After overlap assessment, 65 systematic reviews were chosen for data extraction. The three AEs with the highest median incidence were fatigue (18.3%, interquartile range [IQR] 15.0-28.0%), diarrhea (15.3%, IQR 9.7-29.2%) and rash (14.4%, IQR 10.3-19.2%). The three AEs (high-grade) with the highest median incidence were diarrhea (1.5%, IQR 1.2-6.0%), colitis (1.3%, IQR 0.6-6.1%) and neutropenia (1.2%, IQR 0.4-3.3%). Incidence proportions of high-grade AEs were often considerably lower than all-grade AEs and combination therapy (ICI combinations or combinations of ICI with chemotherapy or targeted therapy) was responsible for some of the highest incidence proportions regardless of AE. Rare AEs and certain cancer subtypes were not well reported. CONCLUSIONS: Early recognition of AEs associated with ICIs requires expertise from diverse specialists, not just oncologists. Greater awareness of potential AEs may result in earlier recognition, appropriate management, and better patient outcomes. PROSPERO REGISTRATION: CRD42021231593.

Attitudes towards open-label versus placebo-control designs in oncology randomized trials: A survey of medical oncologists.

RATIONALE, AIMS AND OBJECTIVES: Randomized trials are considered the gold standard when assessing the efficacy of new therapeutic agents. In clinical situations where no standard of care therapy is approved, randomized trials usually compare experimental agents to either a placebo or an open-label nonintervention arm (i.e., best supportive care). We surveyed Canadian medical oncologists to understand their attitudes towards each design. METHODS: Members of the Canadian Association of Medical Oncologists were invited to participate in an anonymous online survey. Standardized case scenarios were used to determine participants' attitudes regarding the role of open-label versus placebo-controlled trials. RESULTS: A total of 322 medical oncologists and trainees were invited to participate and 86 responded (response rate 27%). Fifty-one (59%) believed that open-label trials are an acceptable alternative to placebo-controlled design when investigating a therapeutic agent in the adjuvant setting. Thirty-eight (49%) deemed it acceptable to compare the investigational agent to an open-label arm instead of a placebo to assess progression-free survival in the metastatic setting. Twenty-eight (38%) of respondents felt that open-label design was acceptable when assessing the quality of life endpoint. Most physicians were unsure whether the US Food and Drug Administration require a placebo-controlled arm in oncology trials. CONCLUSION: Canadian medical oncologists participating in this survey are divided in their opinions regarding the acceptability of an open-label design in randomized-controlled trials, where no standard therapy is approved. Clearer guidance from regulatory bodies on the adequacy of different trial designs is needed.

Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019.

The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2019 was held in Morell, Prince Edward Island, 19-21 September 2019. Experts in medical oncology, radiation oncology, and surgical oncology who are involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics in the management of anal, colorectal, biliary tract, and gastric cancers, including: radiotherapy and systemic therapy for localized and advanced anal cancer; watch and wait strategy for the management of rectal cancer; role of testing for dihydropyrimidine dehydrogenase (DPD) deficiency prior to commencement of fluoropyrimidine therapy; radiotherapy and systemic therapy in the adjuvant and unresectable settings for biliary tract cancer; and radiotherapy and systemic therapy in the perioperative setting for early-stage gastric cancer.

Potential insights from population kinetic assessment of progression-free survival curves.

Progression-free survival (PFS) curves follow first order kinetics on exponential decay nonlinear regression analysis (EDNLRA). Some exhibit 1-phase-decay, some have 2-phase-decay, some are convex. We digitized, performed EDNLRA and generated log-linear plots for 887 published PFS curves for incurable solid tumors treated with various systemic therapies. Proportion of curves fitting 2-phase-decay varied by therapy (p < 0.0001). For 13 therapies, >64 % of PFS curves had 2-phase-decay. This included epidermal growth factor receptor inhibitors in unselected lung cancer patients (some with, some without mutations), immune checkpoint inhibitors, interferon, breast cancer hormonal therapies, and selected others, suggesting 2 distinct, potentially identifiable subpopulations with differing progression rates. For 22 other therapies, <25 % of PFS curves had 2-phase-decay. Only 1 therapy was in the mid-range. Small cell lung and colon carcinomas were particularly likely to yield highly convex curves (p < 0.006), probably from discontinuation of effective therapies. PFS curve shape may yield biological and clinical insights.

Imaging Intensity and Survival Outcomes in High-Risk Resected Melanoma Treated by Systemic Therapy at Recurrence.

BACKGROUND: Intensive imaging in melanoma remains controversial because its survival impact is unknown. We investigated the impact of imaging intensity on the rates of asymptomatic surveillance-detected recurrence (ASDR) and subsequent treatment outcomes in patients with access to immune checkpoint inhibitors (ICIs) and targeted therapy (TT). METHODS: Patients with resected malignant melanoma undergoing imaging surveillance at a single center between 2006 and 2016 were identified. Surveillance and recurrence characteristics (imaging, symptom, treatment, and survival data) were retrospectively collected. Univariate (t test, Chi square test) and multivariate Cox regression analyses were conducted. RESULTS: Of 353 high-risk melanoma patients (stage IIB, 24%; IIC, 19%; IIIA, 27%; IIIB, 16%; IIIC, 14%), 71 (45%) had ASDR and 88 (55%) had symptomatic recurrence (SR). Shorter imaging intervals identified more ASDR (57%, 0-6 months; 34%, 6-12 months; 33%, > 12 months; p = 0.03). ASDR had better prognostic factors than SR [fewer than three metastatic sites (43 vs. 21%, p = 0.003), normal lactate dehydrogenase (LDH; 53 vs. 38%, p = 0.09), brain metastases (11 vs. 40%, p < 0.001)] and received more systemic treatment (72 vs. 49%, p = 0.003; ICIs 55 vs. 31%, p = 0.002; TT 8 vs. 13%, p = 0.41). ASDR had better survival outcomes on ICI treatment (2-year OS, 56 vs. 31%, p < 0.001). Median OS from surveillance start was 39.6 vs. 22.8 months (p < 0.001). ASDR was independently associated with survival (hazard ratio 0.47, 95% confidence interval 0.29-0.78, p = 0.003), adjusting for stage, sex, age, disease burden, LDH, era of recurrence, brain metastases, and ICI/TT treatment. CONCLUSIONS: These real-world data support further study on intensified imaging surveillance protocols for high-risk resected melanoma, as ASDR was associated with superior survival outcomes from ICI therapy.

Correction to: Imaging Intensity and Survival Outcomes in High-Risk Resected Melanoma Treated by Systemic Therapy at Recurrence.

In the original article, the survival curves are missing in Fig. 1c, d.

Docetaxel dose-intensity effect on overall survival in patients with metastatic castrate-sensitive prostate cancer.

BACKGROUND: Several studies assessed the association of docetaxel dose intensity (DI) and efficacy in metastatic castrate-resistant prostate cancer (mCRPC) patients with contradicting conclusions. In this retrospective analysis, we will assess whether the docetaxel DI used in patients with metastatic castrate-sensitive prostate cancer (mCSPC) is associated with overall survival (OS). METHODS: All patients with mCSPC treated at The Ottawa Hospital Cancer Centre that received docetaxel chemotherapy between June 2014 and September 2017 were identified. The association between relative dose intensity (RDI) and OS was assessed using univariate and multivariable Cox model adjusting for age, Gleason score, burden of disease, visceral involvement, de novo metastases and baseline prostate-specific antigen (PSA). RESULTS: Eighty-one patients were included in the analysis. Only 35 patients (43%) were able to complete the planned treatment with a RDI of at least 90%. On a univariate analysis, higher RDI and number of cycles of docetaxel received were associated with longer OS. For every 10% decrease in RDI, the risk of death increased by 23% (HR 1.23, 95% CI 1.09-1.4, P = 0.001). For every increment of one cycle (and up to six), the risk of death decreased by 27% (HR 0.73, 95% CI 0.61-0.88, P = 0.001). On multivariate analysis, reduced RDI was the only predictor significantly associated with OS (HR 1.18, 95% CI 1.02-1.36, P = 0.026). CONCLUSIONS: Our study suggests that in mCSPC, reduced docetaxel RDI is associated with shorter survival. Unnecessary dose reductions, treatment delays and early discontinuation should be avoided. Granulocyte colony-stimulating factor may be considered to maintain standard DI.

Outcomes in Black and White Patients With Metastatic Renal Cell Carcinoma Treated With First-Line Tyrosine Kinase Inhibitors: Insights From Two Large Cohorts.

PURPOSE: To investigate whether black race is an independent predictor of overall survival (OS) in metastatic renal cell carcinoma (mRCC). METHODS: We performed a retrospective 2-cohort (International Metastatic Renal Cell Carcinoma Database Consortium [IMDC] and trial-database) study of patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs). Unmatched (UM) and matched (M) analyses accounting for imbalances in region, year of treatment, age, and sex between races were performed. Cox models adjusting for histology, number of metastatic sites, nephrectomy, and IMDC risk compared time to treatment failure (TTF; IMDC cohort), progression-free survival (PFS; trial-database cohort), and OS. RESULTS: The IMDC cohort included 73 black versus 3,381 (UM) and 1,236 (M) white patients. The trial-database cohort included 21 black versus 1,040 (UM) and 431 (M) white patients. Median OS for black versus white patients was 18.5 versus 25.8 months in the IMDC group and 21.0 versus 25.6 months in the trial-database group. Differences in OS were not significant in multivariable analysis in the IMDC group (hazard ratio [HR]M, 1.0; 95% CI, 0.7 to 1.5; HRUM, 1.1; 95% CI, 0.8 to 1.4) and trial-database (HRM, 1.5; 95% CI, 0.8 to 2.7; HRUM, 1.4; 95% CI, 0.8 to 2.6) cohorts. TTF for black patients was shorter in the UM IMDC cohort (HRUM, 1.4; 95% CI, 1.1 to 1.8; P = .003), but not in the M analysis. PFS was shorter for black patients in both analyses in the trial-database cohort (HRM, 2.3; 95% CI, 1.4 to 3.9; P = .002; HRUM, 2.3; 95% CI, 1.4 to 3.9; P = .002). CONCLUSION: Black patients had more IMDC risk factors and worse outcomes with TKIs versus white patients. Race was not an independent predictor of OS. Strategies to understand biologic determinants of outcomes for minority patients are needed to optimize care.

A novel, more reliable approach to use of progression-free survival as a predictor of gain in overall survival: The Ottawa PFS Predictive Model.

Progression-free survival (PFS) hazard ratios and gain in median PFS are suggested predictors of overall survival (OS) gain (with gain defined as experimental arm minus control arm values). We assessed use of half-lives (time to progression/death of half remaining patients). We reviewed randomized trials from Journal of Clinical Oncology and New England Journal of Medicine, 01/2012-06/12/2017 (discovery series) and 01/01/2007-12/31/2011 (first validation series). If PFS or OS gains were significant, we used PFS/OS curve nonlinear regression analysis to estimate half-lives and defined "half-life gain" as experimental minus control arm half-life. With low crossover and significant PFS differences, PFS half-life gains ≥1.5 months had positive-predictive-values for OS gains ≥2 months of 79 % and 86 % and PFS half-life gains <1.5 months had negative-predictive-values for OS gains <2 months of 95 % and 75 %, in discovery and validation series, respectively. PFS half-life gains more reliably predicted OS gains than PFS hazard ratios or gains in median PFS. Findings were confirmed in a second validation series.