Cisplatin-Based versus Carboplatin-Based Chemotherapy for Extra-Pulmonary Neuroendocrine Carcinomas; A Real-World Study.

Objective: To assess the survival differences between cisplatin/etoposide versus carboplatin/etoposide chemotherapy regimens in the management of extra-pulmonary neuroendocrine carcinomas (NECs). Methods: Administrative cancer care databases in the province of Alberta, Canada were reviewed, and patients with extra-pulmonary NECs (including those with small cell and large cell neuroendocrine carcinomas) who were treated with either cisplatin/ etoposide or carboplatin/ etoposide, 2004-2019, were reviewed. Kaplan-Meier survival estimates were used to compare the survival outcomes according to the type of platinum agent, and multivariable Cox regression analysis was used to assess the impact of the type of platinum agent on overall survival outcomes. Results: A total of 263 eligible patients were included in this analysis. These include 176 patients who received cisplatin/ etoposide and 87 patients who received carboplatin/etoposide. Using Kaplan-Meier survival estimates, patients treated with cisplatin have better overall survival compared to patients treated with carboplatin (P=0.005). Multivariable Cox regression analysis suggested that the following factors were associated with worse overall survival: higher Charlson comorbidity index (HR: 1.17; 95% CI: 1.05-1.30), gastrointestinal primary site (HR: 1.55; 95% CI: 1.12-2.14), stage IV disease (HR: 1.75; 95% CI: 1.28-2.38) and use of carboplatin (HR: 1.40; 95% CI: 1.02-1.92). Conclusions: The current study suggested that cisplatin/etoposide might be associated with better overall survival compared to carboplatin/etoposide among patients with extra-pulmonary NECs. It is unclear if this is related to differences in inherent responsiveness to the two platinum agents, or due to differences in comorbidity burden between the two treatment groups.

Chemotherapy in Neuroendocrine Tumors

The role for cytotoxic chemotherapy in patients with well-differentiated neuroendocrine tumors (NETs) remains debated. Compared to patients with poorly differentiated neuroendocrine carcinomas (NECs) where chemotherapy is utilized ubiquitously, chemotherapy may play a more select role in patients with certain types of NETs (e.g., pancreatic tumors, higher grade tumors, and tumors possessing DNA damage repair defects). The primary types of chemotherapy that have been tested in patients with NETs include alkylating agent- and platinum agent-based combinations. Across regimens, chemotherapy appears to elicit greater antitumor activity in patients with pancreatic or grade 3 NETs. The role for chemotherapy in lower grade extra-pancreatic NETs remains undefined. Furthermore, while chemotherapy has demonstrated clinically meaningful benefit for patients in the systemic setting, its role in the adjuvant or neoadjuvant setting is as-of-yet undetermined. Finally, efforts to combine chemotherapy with targeted therapy and peptide receptor radionuclide therapy are ongoing, in hopes of improving the cytoreductive treatment options for patients with NETs.

Efficacy of Chemotherapy for Malignant Pleural Mesothelioma According to Histology

PurposeCheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. MethodsClinical records of all MPM patients diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan-Meier method. Results189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95%CI17.2-24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in nonepithelioid patients (HR2.25 CI95% 1.4-3.4; p<0.001). Median PFS for patients with epithelioid tumors treated with chemotherapy was 4.8 months versus 3.6 months in nonepithelioid (HR1.5 CI95% 1.0-2.3; p=0.03). The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was not a predictive factor for the platinum agent sensitivity (p of interaction PFS=0.09, p of interaction OS=0.65). Conclusions In our series, patients with nonepithelioid tumors presented worse prognosis. Although epithelioid tumors exposed to cisplatin had higher PFS, histology was not a clear predictor of chemotherapy efficacy.

Cisplatin versus carboplatin for the treatment of limited-stage small cell lung cancer (LS-SCLC).

8565 Background: Standard of care therapy for LS- SCLC is concurrent chemo-radiation (CRT) with a platinum-etoposide backbone. Cisplatin is traditionally the preferred platinum agent in the curative intent setting. Data comparing the efficacy of the less toxic carboplatin to cisplatin in LS-SCLC are lacking. Methods: Data from the National VA Cancer Cube were collected. Pathologically confirmed cases of LS-SCLC that received concurrent CRT with platinum-based multiagent chemotherapy were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Survival curves were compared by a Wald test. Results: 801 LS-SCLC patients who received carboplatin-based therapy (Carbo-SCLC) and 1018 who cisplatin-based therapy (Cis-SCLC) were included in the analysis. Median OS with Carbo-SCLC and Cis-SCLC were 2.13 years (95% CI 1.97-2.31) and 2.24 years (95% CI 2.09-2.4), respectively (HR=1.04;95% CI, 0.94-1.16; p=0.46). Subset analysis showed similar median OS for Carbo-SCLC and Cis-SCLC in patients with ECOG-PS of 0, 1 and 2, as well as patients in their 50s, 60s and >70. Multivariable regression analysis accounting for age and ECOG-PS shows a HR of 0.99 (95% CI 0.86-1.14; p=0.91). Conclusions: Concurrent CRT with carboplatin-etoposide was associated with similar OS compared to cisplatin-etoposide in LS-SCLC, irrespective of PS and age. Carboplatin’s advantageous toxicity profile and comparable OS indicate that it is an acceptable choice of platinum for LS- SCLC.[Table: see text]

Survival Outcomes Following Combination of First-Line Platinum-Based Chemotherapy with S-1 in Patients with Advanced Gastric Cancer

The efficacy of S-1 combined with a platinum agent in the first-line setting and in patients with advanced gastric adenocarcinoma has been previously demonstrated in randomized clinical trials. However, real-world data regarding S-1 efficacy in European patients remains limited. In the present study, we reviewed the data of a European cohort of patients with advanced gastric cancer treated with first-line therapy consisting of S-1 in combination with a platinum agent. Forty-eight patients (29 with locally advanced/inoperable and 19 with metastatic disease) were treated with S-1 plus oxaliplatin (33 patients) or S1 plus cisplatin (15 patients). The Cox regression analysis, adjusted with propensity score, indicated that the use of cisplatin as compared to oxaliplatin was associated with increased risk of death (HR 9.634, p = 0.000). Four SAEs (serious adverse events) GIII were recorded (1 fatigue, 1 neutropenia, 1 anemia, 1 diarrhea) in 3 patients. S-1 combination with a platinum agent in the first-line setting in European patients with advanced gastric cancer results to similar survival outcomes and toxicity with previously reported data from Asian populations. S-1 combination with oxaliplatin seems to be associated with superior efficacy as compared to cisplatin.

Real-world adoption of PD-L1 testing in metastatic urothelial carcinoma.

e19184 Background: The role of PD-L1 testing in locally advanced (LA) or metastatic urothelial carcinoma (mUC) is not currently well-defined, except in cisplatin-ineligible patients (pts). IMVigor130 trial data are the first to suggest cisplatin-eligible PD-L1 positive pts may also benefit from immunotherapy (IO) (ESMO LBA14_PR, 2019). As clinical data accumulate on the influence of PD-L1 expression on LA/mUC pt outcomes with IO, we assessed medical oncologists’ (ONCs) PD-L1 testing perceptions and practices. Methods: ONCs completed a longitudinal, online self-report survey fielded from August 22 to September 23, 2019, prior to release of IMVigor130 data. Baseline results are reported. Descriptive statistics and bivariate comparisons by practice setting were conducted. Results: ONCs (N = 203) had a mean of 15 years in practice; a majority (64%) practice in the community. ONCs tested most LA/mUC pts, but initiated treatment for about a third before receiving results (Table). Half believe PD-L1 testing in LA/mUC will increase over time; this view was more common for ONCs who do not (n = 55) vs. do (n = 148) order PD-L1 testing as standard for LA/mUC pts (55% vs. 49%). Most ONCs reported that pts in an IO + chemotherapy trial arm should be stratified by PD-L1 status (74%), but not platinum agent (69%). Common barriers to more LA/mUC pts (n = 92) getting a PD-L1 test were limited biopsy sample (54%), lack of influence on treatment decisions (54%), and treatment initiation urgency (30%). ONCs varied little by practice setting. Conclusions: PD-L1 testing has been adopted by ONCs for most of their LA/mUC pts. However, ONCs report limited biopsy sample and lack of influence on treatment decisions as barriers to testing more LA/mUC pts, supporting their initiation of therapy prior to receipt of results and desire for trial data to be stratified by PD-L1 status. Results suggest PD-L1 expression is not yet a key driver in treatment decisions. Given the variability in self-reported responses, results should be interpreted with this limitation in mind. [Table: see text]