Sameer Ghate

Real-World Survival Outcomes and Prognostic Factors Among Patients Receiving First Targeted Therapy for Advanced Renal Cell Carcinoma: A SEER-Medicare Database Analysis

Background The real‐world survival outcomes and prognostic factors among patients receiving first‐line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. Patients and Methods Adult patients diagnosed with RCC and treated with first‐line targeted therapy were identified from the Surveillance, Epidemiology, and End Results–Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006‐2009) or late (2010‐2012) targeted therapy era cohorts by the year of the first‐line targeted therapy initiation. Overall survival (OS) was measured from first‐line targeted therapy initiation and compared between the 2 cohorts using Kaplan‐Meier analyses. The prognostic factors for OS were assessed using a multivariable‐adjusted Cox model. Results A total of 604 and 641 aRCC patients (mean age, 68 years; ˜60% male in both cohorts) initiated first‐line targeted therapy during the early and late targeted therapy eras, respectively. OS was significantly longer in the late than in the early targeted therapy era. Higher tumor grades (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.31‐2.00) and lung (HR, 1.27; 95% CI, 1.06‐1.53), bone (HR, 1.37; 95% CI, 1.13‐1.66), and liver (HR, 1.42; 95% CI, 1.10‐1.84) metastases were associated with significantly shorter OS. Previous nephrectomy (HR, 0.55; 95% CI, 0.42‐0.72) and pazopanib as first‐line targeted therapy relative to sorafenib (HR, 0.56; 95% CI, 0.37‐0.85) or sunitinib (HR, 0.65; 95% CI, 0.44‐0.95) were associated with significantly longer OS. Conclusion The results of these real‐world analyses suggest progress in aRCC management and identified positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bone, or liver metastasis) prognostic factors among patients receiving first‐line targeted therapy. Micro‐Abstract Using the Surveillance, Epidemiology, and End Results–Medicare database, we assessed overall survival (OS) among renal cell carcinoma patients who had initiated first‐line targeted therapy. OS was significantly longer in the late (2010‐2012) versus early (2006‐2009) targeted therapy era. Positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bong, or liver metastases) OS prognostic factors were identified.

Patterns of care among patients receiving sequential targeted therapies for advanced renal cell carcinoma: A retrospective chart review in the USA

To assess real‐world treatment patterns of targeted therapies after failure of first‐line tyrosine kinase inhibitors in patients with advanced renal cell carcinoma.

Results of a Qualitative Study to Develop a Patient Reported Outcome Measure for Patients with 4 Subtypes of Soft Tissue Sarcoma

Objective The objective of this research was to develop a disease-specific symptom inventory for soft tissue sarcoma. Methods Literature review and clinical expert and patient interviews were conducted to determine disease-specific symptoms important to patients with one of the four STS subtypes. Clinical experts identified the most relevant STS symptom items from the item pool developed from literature review. Concept elicitation interviews were conducted with patients to elicit their STS symptom experiences followed by a completion of the draft symptom list via web survey. A cognitive interview was conducted on the comprehension and importance of the symptom items. Results Eighty-three symptom items were compiled and discussed with three clinical experts who identified 26 symptoms specific to the four STS subtypes. A total sample of 27 STS participants with self-reported leiomyosarcoma (74%), undifferentiated sarcoma (15%), synovial sarcoma (7%), or liposarcoma (4%) diagnosis completed the web survey and 10 were interviewed. The draft 12-item STS-specific symptom inventory includes abdominal pain, pressure in abdomen, early satiety, bloating, gastrointestinal pain, muscle pain, bone pain, heavy menstrual flow, shortness of breath, chest pain, cough, and painful menstruation. Conclusion A number of symptoms are common across STS subtypes and may form a single STS symptom inventory.

Stage III melanoma incidence and impact of transitioning to the 8th AJCC staging system: a US population-based study

AIM To estimate incidence of stage III melanoma using the American Joint Committee on Cancer (AJCC) staging, 7th and 8th edition. PATIENTS & METHODS The SEER US cancer registry was analyzed (2010-2014). AJCC7 stages were recorded in the data; AJCC8 stages were inferred. RESULTS Of 106,195 melanoma patients, 7669 and 7342 had stage III melanoma by AJCC7 and AJCC8, respectively (95% overlap). Nearly 30% of patients with AJCC7 stage III melanoma were reclassified in a higher stage III group by AJCC8 versus 7% in lower stage group. Regardless of the AJCC edition, incidence of stage III melanoma has increased from 2010 to 2014 both overall and within each stage III group. CONCLUSION Providing appropriate management to this growing population of high-risk patients is a priority.

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy

Abstract Objective: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D + T; oral) and those initiated on 1 L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous). Methods: Patients with melanoma initiated on D + T or N/P from Q1/2014 to Q2/2016 (defined as 1 L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D + T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1 L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates). Results: Of the 445 patients included, 202 and 243 were initiated on D + T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1 L therapy than those initiated on D + T (difference = 18.6 visits PPY [95% CI = 16.0–21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference = 8.1 visits PPY [95% CI = 1.9–13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1 L therapy). Conclusions: HRU during 1 L therapy was generally similar between patients initiated on D + T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.

Predictors of Long-Term Response With Pazopanib in Patients With Advanced Renal-Cell Carcinoma

Micro‐Abstract Few reports of long‐term response with pazopanib in advanced renal‐cell carcinoma (aRCC) exist, and associated factors are unknown. A total of 153 first‐line pazopanib‐treated patients with aRCC were evaluated for long‐term response (progression‐free survival ≥ 18 months) in a real‐world setting. An Eastern Cooperative Oncology Group performance status of 0 and nephrectomy history were significant predictors of long‐term response in this patient population. Background: Pazopanib is among the current standards of care for first‐line treatment of patients with unresectable advanced renal‐cell carcinoma (aRCC) or metastatic renal‐cell carcinoma. This real‐world study aimed to characterize those with long‐term response to pazopanib in the treatment of aRCC in a community oncology setting, and to identify predictors of long‐term response. Patients and Methods: aRCC patients treated with first‐line pazopanib were classified as having long‐term or non–long‐term response (progression‐free survival [PFS] of ≥ 18 or < 18 months, respectively). Baseline patient demographics and clinical characteristics were evaluated and compared between the 2 groups. Differences in PFS and overall survival were also evaluated. Results: A total of 153 eligible patients were identified, of which 33 (21.6%) and 120 (78.4%) patients were identified as having disease with long‐term and non–long‐term response, respectively. The median PFS for those with long‐term response was 27.2 months (95% confidence interval [CI], 23.0‐35.2) versus 6.9 months (95% CI, 5.0‐8.6) for those with non–long‐term response. Median overall survival was not reached (NR) for those with long‐term response (95% CI, NR to 39.1) compared to 15.3 months (95% CI, 12.3‐21.6) for those with non–long‐term response. Baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 (vs. ECOG PS of 1 and ≥ 2) and history of nephrectomy were identified as significant predictors of long‐term response to pazopanib. Conclusion: In aRCC patients treated with first‐line pazopanib, 22% had a long‐term response. Significant predictors of long‐term response included an ECOG PS of 0 and a history of nephrectomy.

Abstract 1209: Patterns of treatment with immune check point inhibitors and targeted therapy in patients with metastatic melanoma presumed BRAF V600 positive

Background: Immune check point inhibitors (I-O) and targeted therapies (TT) have changed the treatment landscape for patients with metastatic melanoma (MM), particularly for patients with BRAFV600 (BRAF) mutation who are eligible for both types of treatment after a diagnosis of MM. The aim of the current study was to describe patterns of treatment with I-O and TT in first line (1L) and subsequent lines of therapy for MM in a sample of patients presumed BRAF positive. Methods: Adults with MM initiated on I-O (ipilimumab, pembrolizumab, nivolumab) and TT (vemurafenib, dabrafenib, trametinib) therapies in 1L were identified in Symphony Health Solutions9 Integrated Dataverse (Q1/2014 - Q1/2017; n = 4,196), the largest pharmacy database in the US. Lines of pharmacological therapy were investigated from the first I-O/TT (index date) until the end of the observation period using an algorithm that relies on prescription/administration dates, days of supply and periods without any therapies. Patients were presumed BRAF positive if they received TT in at least one line of MM therapy. All patients in this analysis were required to have ≥ 2 lines of therapy for MM. Results: Of 366 presumed BRAF patients in the study sample, 110 (30%) and 256 (70%) were initiated on I-O and TT in 1L, respectively. The table below presents treatment patterns in 1L, 2L, and 3L for MM. The distribution of I-O vs TT was 30% vs. 70% in 1L, 25% vs. 57% in 2L, and 41% vs. 39% in 3L (table). Conclusions: This real-world data study showed dabrafenib+trametinib was the most common treatment for patients with MM presumed BRAF positive, even in the era of I-O availability. During the study period (years 2014-2017), ipilimumab continued to be the most common I-O therapy used in 1L and 2L among presumed BRAF patients. Citation Format: Sameer Ghate, Antonio Nakasato, Raluca Ionescu-Ittu, Sherry Shi, Briana Ndife, Rebecca Burne, Francois Laliberte, Mei Sheng Duh. Patterns of treatment with immune check point inhibitors and targeted therapy in patients with metastatic melanoma presumed BRAF V600 positive [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1209.