First-line Chemotherapy Group Research Articles

Major adverse cardiovascular events in advanced-stage lung cancer: a multicenter cohort study.

Lung cancers are common worldwide. First-line targeted therapy and chemotherapy are both standard treatments in the current guidelines. With the development of new anticancer therapy, the lifespan of patients with late-stage lung cancer has increased. Cardiovascular events can occur during cancer treatment. This observational study aimed to report the incidence of major adverse cardiovascular events (MACE) after cancer treatment using real-world data. Patients diagnosed with advanced-stage lung cancer between January 2011 and December 2017 were enrolled. Data were collected from the Chang Gung Research Database (CGRD). Retrospective cohort study. Baseline characteristics, clinical stages, pathologies, and outcomes were retrieved from the CGRD. We identified 4406 patients with advanced lung cancer, of whom 2197 received first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy and 2209 received first-line platinum-based chemotherapy. Most patients in the first-line EGFR-TKI group were never-smokers (74.9%), whereas those in the first-line chemotherapy group were ever-smokers (66.0%). The incidence of MACE was not significantly different between the two groups (12.0% versus 11.9%, p = 0.910). However, the incidence of ischemic stroke was higher in the first-line EGFR-TKI group than in the first-line chemotherapy group (3.9% versus 1.9%, p < 0.001). MACEs are common in patients with advanced-stage lung cancer during treatment. The incidence of MACE was similar between the first-line EGFR-TKI therapy and first-line chemotherapy groups. Although more patients in the EGFR-TKI group were female and never-smokers, the risk of ischemic stroke was higher in patients who received first-line EGFR-TKI therapy than in those who received first-line chemotherapy.

Transportability of Overall Survival Estimates From US to Canadian Patients With Advanced Non–Small Cell Lung Cancer With Implications for Regulatory and Health Technology Assessment

The external validity of survival outcomes derived from clinical practice data from US patients with advanced non-small cell lung cancer (NSCLC) is not known and is of potential importance because it may be used to support regulatory decision-making and health technology assessment outside of the US. To evaluate whether overall survival (OS) estimates for a selected group of patients with advanced NSCLC from a large US clinical practice database are transportable to Canadian patients receiving the same systemic therapies. This retrospective multicenter cohort study used transportability analysis to assess whether adjustment for pretreatment characteristics of eligible patient cohorts could reliably approximate OS estimated from US-based samples to Canadian populations. A total of 17 432 eligible adult patients who were diagnosed de novo with advanced NSCLC on or after January 1, 2011, were included in the analysis and followed up until September 30, 2020. Because data on race and ethnicity were available in the US database but not the Canadian database and because racial and ethnic distribution was likely to be similar between US and Canadian patients, these characteristics were not analyzed. Initiation of platinum-doublet chemotherapy or pembrolizumab monotherapy as first-line systemic treatment for advanced NSCLC. OS measured from the time of initiation of the respective treatment regimen. Among 17 432 eligible patients, 15 669 patients from the US and 1763 patients from Canada were included in the analysis. Of those, 11 863 patients (sample size-weighted estimates of mean [SD] age, 68.0 [9.3] years; 6606 [55.7%] male; 10 100 from the US and 1763 from Canada) were included in the subset of patients with complete data for baseline covariates. A total of 13 532 US patients received first-line chemotherapy, and 2137 received first-line pembrolizumab monotherapy. Of those, 8447 patients (62.4%) in the first-line chemotherapy group and 1653 patients (77.3%) in the first-line pembrolizumab group had complete data on baseline covariates for outcome model estimation. A total of 1476 Canadian patients who received first-line chemotherapy and 287 patients who received first-line pembrolizumab monotherapy were identified from the target population. After standardization to baseline patient covariates in the Canadian cohorts, transported OS estimates revealed a less than 5% mean absolute difference from the observed OS in the target population (0.56% over 60 months of follow-up in the first-line chemotherapy group and 4.54% over 30 months of follow-up in the first-line pembrolizumab group). Negative control analysis using a mismatched outcome model revealed a 6.64% discrepancy and an incompatible survival curve shape. The results were robust to assumptions of random missingness for baseline covariates, to unadjusted differences in baseline metastases and comorbidities, and to differences in the standard of care between the US and Canada related to administration of second-line anti-programmed cell death 1 ligand 1 immunotherapy for patients who initiated first-line chemotherapy. The results of this cohort study suggest that, under specific circumstances, OS estimates from US clinical practice data can be adjusted using baseline clinical characteristics to closely approximate OS in selected groups of Canadian patients with advanced NSCLC. These results may have implications for regulatory decision-making and health technology assessment in target populations outside of the US.

Real-world Experience of Olaparib Treatment in Patients with Ovarian Cancer: A Chinese Multicenter Study.

The objective of this study was to evaluate the real-world application, efficacy, and safety data of olaparib for maintenance therapy and active treatment in patients with ovarian cancer in China. Patients with ovarian cancer from 17 institutions in China treated with olaparib as maintenance or active therapy from January 2018 to March 2020 were included in this study. The medical records were reviewed, and follow-up information was collected for analysis of the patients' clinicopathologic characteristics as well as the effectiveness and safety of olaparib. A total of 251 patients receiving olaparib were included, with 84 as maintenance therapy after first-line chemotherapy (FL-M), 97 as maintenance therapy after platinum-sensitive recurrence (PSR-M), and 70 as active treatment (AT). The probability of progression-free survival (PFS) at 12 months was 87.6% in the FL-M group and 63.8% in the PSR-M group. According to the multivariate analysis, complete response (CR) to chemotherapy for the PSR-M patients was the only factor affecting the PFS (HR = 0.414, P = 0.014), and platinum sensitivity was the only factor affecting PFS improvement in the AT group (HR = 0.317, P = 0.009). In the AT group, the objective response rate was 37.1%, the CR rate was 7.1%, and 30% of the patients had stable disease. Eight (3.2%) patients discontinued olaparib due to toxicity. Anemia was the most common adverse event. In conclusion, olaparib is effective and well tolerated in the real-world setting of ovarian cancer treatment. Platinum sensitivity is positively correlated to the effectiveness of olaparib in both maintenance and active treatment.

Multiple treatment modalities for brain metastasis in patients with EGFR-mutant non-small-cell lung cancer.

BackgroundThere are many controversies concerning the best management of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with brain metastases (BMs). The use of upfront EGFR tyrosine kinase inhibitors (TKIs) and the withholding of local therapies or upfront radiation therapies (RTs) remain controversial. Available treatment options include local therapies such as whole-brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and surgery, EGFR-TKIs, and chemotherapy. However, the optimal management of combination therapies is still under consideration.Patients and methodsA total of 45 EGFR-mutated NSCLC patients with BMs were included. All patients successively received EGFR-TKIs, RT (WBRT or SRS), and chemotherapy between 2010 and 2015 at Zhejiang Cancer Hospital. Patient follow-up was conducted by telephone until February 2017. The treatment response was evaluated, and survival data were collected and analyzed by Kaplan–Meier analysis and the Cox regression method.ResultsThe median overall survival (OS) was 28 months. Patients with the exon 19 deletion showed the strongest trend toward a longer median OS compared to patients with the exon 21 L858R mutation (not reached vs 26.5 months, P=0.0969). There was no difference in OS between the upfront RT group and the deferral group (26.5 vs 28 months, P=0.57), and similar results were found between the first-line chemotherapy group and the EGFR-TKI group (28 vs 23.2 months, P=0.499). In multivariate analysis, the prognosis correlated with EGFR mutation type (P=0.017).ConclusionEGFR-mutant NSCLC patients with BM benefited from the combination and sequential therapies of EGFR-TKIs, chemotherapy, and RTs. Patients with the EGFR exon 19 deletion may have a better OS. However, the optimal timing of RT interval remains to be explored.

P-0119 Beneficial Trends of Second Line Chemotherapy in Advanced Pancreatic Cancer

IntroductionDespite the lack of high-quality clinical trial data suggesting that second-line chemotherapy (SLC) may affect survival on metastatic pancreatic cancer (mPC), most of centers utilizes them after the failure of initial treatment in patients who maintain a good performance status. The aim of the present study was to review our institutional experience with SLC and estimate its role in overall survival (OS). MethodsWe performed a retrospective matched case-control analysis based on search of medical records in 106 consecutive patients with mPC at our institution. Patients received first line chemotherapy (FLC) and SLC (n=49) or FLC only (n =57) from September 2005 to December 2010. Case matching was performed with respect to age (< 60y versus≥60y), topography (head of the pancreas versus body or tail), sites of metastasis. Overall survival was analyzed by Kaplan-Meier method ResultsMedian age was 63 (32-86) and 60 (38-85) for SLC group and FLC group respectively. There was no significant difference between the two groups regarding topography, TNM stage at diagnosis, and sites of metastasis. The main site of metastasis was the liver (24.4%), followed by peritoneum (2.8%). Median follow-up of both groups was 8.4 months (0.23-54.93 months). First line treatment consisted of Gemcitabine (55.1% x 49.1%) and Gemcitabine+Cisplatin (18.4%x14%) in SLC and FLC group respectively. The most used second line treatment was Capecitabine (32.7%), followed by FOLFOX (16.3%), and Fluorouracil (10.2%). The Kaplan-Meier estimate of the overall median survival, 1-year and 2-years survival rate was 15.72 months versus 7.2 months (P=0,021), and 60% vs 32%, and 30% vs 19% in SLC and FLC group, respectively. ConclusionOur result suggests that second-line chemotherapy may be beneficial to improve overall survival in patients with advanced pancreatic cancer. It's important that new and ongoing clinical trials clarify which is the best chemotherapy scheme in this setting.

Beneficial trends of second-line chemotherapy in advanced pancreatic cancer.

e14680 Background: Despite the lack of high-quality clinical trial data suggesting that second-line chemotherapy (SLC) may affect survival on metastatic pancreatic cancer (mPC), most of centers utilizes them after the failure of initial treatment in patients who maintain a good performance status. The aim of the present study was to review our institutional experience with SLC and estimate its role in overall survival (OS). Methods: We performed a retrospective matched case-control analysis based on search of medical records in 106 consecutive patients with mPC at our institution. Patients received first line chemotherapy (FLC) and SLC (n = 49) or FLC only (n =57) from September 2005 to December 2010. Case matching was performed with respect to age (&lt; 60y versus ≥ 60y), topography (head of the pancreas versus body or tail), sites of metastasis. Overall survival was analyzed by Kaplan-Meier method. Results: Median age was 63 (32-86) and 60 (38-85) for SLC group and FLC group respectively. There was no significant difference between the two groups regarding topography, TNM stage at diagnosis, and sites of metastasis. The main site of metastasis was the liver (24,4%), followed by peritoneum (2,8%).Median follow-up of both groups was 8.4 months (0.23m-54.93m). First line treatment consisted of Gemcitabine (55.1% x 49.1%) and gemcitabine + cisplatin (18.4%x14%) in SLC and FLC group respectively. The most used second line treatment was Capecitabine (32.7%), followed by Folfox (16.3%), and Fluoracil (10.2%). The Kaplan-Meier estimate of the overall median survival, 1-year and 2-years survival rate was 15.72 months versus 7.2 months (p:0.021), and 60% vs. 32%, and 30% vs. 19% in SLC and FLC group, respectively. Conclusions: Our result suggests that second-line chemotherapy may be beneficial to improve overall survival in patients with advanced pancreatic cancer. It’s important that new and ongoing clinical trials clarify which is the best chemotherapy scheme in this setting.

Management of neuroblastoma: a study of first- and second-line chemotherapy responses, a single institution experience

Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission. The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24-60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P&lt;0.01).

Management of neuroblastoma: a study of first- and second-line chemotherapy responses, a single institution experience.

Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission.The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24–60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P<0.01).

Cetuximab-based Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: Experience From an Area in Which Betel Nut Chewing Is Popular

This study was undertaken to evaluate the efficacy and safety of cetuximab-based therapy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) in an area in which betel nut chewing is popular. Twenty-five patients were enrolled in the study from 2004 to 2008, of whom 13 received first-line cetuximab plus chemotherapy and 12 received second-line cetuximab with or without chemotherapy after the failure of cisplatin. In the first-line chemotherapy group, the overall response [complete response (CR) plus partial response (PR)] was 54% and disease control rate [CR + PR + stable disease (SD)] was 62%. In the cisplatin-failure therapy group, the overall response was 16.7% and disease control rate was 50%. Median overall survival (OS) and time to progression (TTP) in the first-line chemotherapy group were 857 days and 147 days, respectively. In the cisplatin-failure therapy group, median OS and TTP were 371 days and 136 days, respectively. The most common grade 3/4 toxicity in both groups of patients was infection/fever (23% in the first-line group, 50% in the cisplatin-failure group), followed by neutropenia (23% in the first-line group, 25% in the cisplatin-failure group). Cetuximab-based therapy is an effective and safe treatment choice for recurrent/metastatic HNSCC in areas where betel nut chewing is popular.

S-1 Monotherapy in Patients with Advanced Biliary Tract Cancer

Objective: The aim of this study was to evaluate the efficacy and safety of single-agent S-1 in patients with advanced biliary tract cancer. Methods: S-1 was administered orally at a dose of 80 mg/m² for 28 days, followed by 14 days of rest (1 cycle); treatment was repeated until disease progression, unacceptable toxicity, or patient refusal. Results: Forty-five patients were enrolled between January 2005 and June 2008. Among these, 29 patients received S-1 as first-line chemotherapy and 16 patients received S-1 as second-line chemotherapy. The response rates for first- and second-line chemotherapy were 17.2 and 18.8%, respectively. The median times to progression for the first- and second-line chemotherapy groups were 4.2 and 5.5 months (p = 0.91), respectively. The median overall survival and 1-year survival rate for each group were 8.7 and 8.0 months and 42.2 and 38.2%, respectively (p = 0.62). Only the first-line chemotherapy group experienced grade 3/4 toxicities, including leukopenia (6.9%), neutropenia (10.3%), anemia (6.9%), thrombocytopenia (10.3%) and total bilirubin elevation (3.4%). Conclusion: S-1 monotherapy is a feasible and moderately efficacious treatment for advanced biliary tract cancer, as a first- or second-line chemotherapy regimen.