Comparison of real-life data from patients with NGS panel negative and KRAS mutation positive metastatic lung adenocarcinoma

2021 ◽  
pp. 030089162199644
Author(s):  
Ali Gökyer ◽  
Ahmet Küçükarda ◽  
Osman Köstek ◽  
İvo Gökmen ◽  
Erkan Özcan ◽  
...  

Objective: To evaluate clinical and demographic characteristics and the results of cytotoxic treatments of KRASG12C, KRASother, and next-generation sequencing (NGS) panel negative patients. Methods: NGS data of 1264 patients with non-small cell lung cancer were retrospectively evaluated. Among these patients, the mutation distributions of 1081 patients with metastatic lung adenocarcinoma were analyzed. A total of 150 patients with negative NGS panel or mutant KRAS followed up in our clinic were included. Clinical features, overall survival, first-line chemotherapy responses, and progression-free survival of NGS panel negative, KRASG12C, and KRASother groups were compared. Results: In 1081 patients who underwent NGS from tumor tissue with the diagnosis of metastatic lung adenocarcinoma, 296 (27%) NGS panel negative and 276 (26%) KRAS mutant patients were detected. Among these patients, 150 patients whose data were available were 71 (47.3%) NGS panel negative, 54 (36%) KRASother, and 25 (16.7%) KRASG12C. Clinical features, brain metastasis, and first-line chemotherapy response were similar among groups. Bone metastases were detected more often in the NGS panel negative group ( p = 0.03). The median follow-up was 8.4 months. Overall, 107 deaths had occurred at the time of analysis. There was no difference in overall survival ( p = 0.56) or progression-free survival ( p = 0.71) among NGS panel negative, KRASother, and KRASG12C patients. Conclusion: There is no difference in overall survival, first-line chemotherapy response, or progression-free survival among patients with NGS panel negative, KRASG12C, or KRASother metastatic lung adenocarcinoma. Bone metastases were observed more frequently in the NGS panel negative group.

2005 ◽  
Vol 23 (33) ◽  
pp. 8322-8330 ◽  
Author(s):  
Ruth E. Langley ◽  
James Carmichael ◽  
Alison L. Jones ◽  
David A. Cameron ◽  
Wendi Qian ◽  
...  

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.


Author(s):  
Hong Chuyen Nguyen Thi

Purpose:to study clinical and subclinical characteristics in advanced stage gastric cancer patients and to evaluate response rate, overall survival, progression free survival and toxicities on advanced stage gastric cancer patients treated with first line chemotherapy using epirubicin, oxaliplatin, capecitabin Methods: A retrospective case series study with 134 advanced stage gastric cancer patients on first line chemotherapy using epirubicin, oxaliplatin, capecitabin recruited from oncology department, the Hospital of Hue University of Medicine and Pharmacy and Cancer Center at Hue Central Hospital during January 2015 to June 2019. Results: Patient’s mean age was 54,9; men/women was 2,52/1. The most frequent clinical symptom reported was epigastric pain 81,3%. KPS 80-90% presented in almost patient (93.3%). The most common site of cancer was pyloric antrum (61,9%). 58,2% patients had distant metastasis disease which liver was the most frequent site. The overall response rate, partial response rate, complete response rate were 49,2%, 42,5%, 6,7% respectively. The median progression free survival was 8,6 ± 0,15 months and the overall survival was 10,7 ± 1,1 months. The pathologic type and combined salvage surgery status were response correlated factors. Grade 3, 4 toxicities in term of hematology, liver and kidney function were only exhibited in a few cases. Patients were tolerated well with chemotherapy. No deaths related to chemotherapy. Conclusions: This study shows that EOX regimen was safe and effective. As a results, we can apply this for first line pallative chemotherapy on advanced stage gastric cancer which KPS ≥70%.


2016 ◽  
Vol 65 ◽  
pp. 11-20 ◽  
Author(s):  
Tsuyoshi Hamada ◽  
Yousuke Nakai ◽  
Hiroyuki Isayama ◽  
Hideo Yasunaga ◽  
Hiroki Matsui ◽  
...  

2016 ◽  
Vol 9 (3) ◽  
pp. 610-628 ◽  
Author(s):  
Lu Xie ◽  
Wei Guo ◽  
Xiaodong Tang ◽  
Yi Yang ◽  
Jie Xu

Patients who mildly progressed after first-line chemotherapy were administered arsenic trioxide (ATO) 5–10 mg intravenously daily. Thirty-nine patients were finally enrolled in the study, of whom 19 patients received first-line chemotherapy with ATO infusion while 20 patients did not. Progression-free survival at 4 months was 89.2 and 62.7% (p = 0.043) for the ATO group and the control group, respectively, while the 2-year overall survival was 61 and 16.4% (p = 0.032).


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15132-e15132
Author(s):  
Jangho Cho ◽  
Jae Yun Lim ◽  
Jae Yong Cho

e15132 Background: Gemcitabine is the standard treatment for advanced pancreatic cancer. Though capecitabine and erlotinib are accepted as combination agent with gemcitabine, those two combination regimens have not been compared directly in clinical trial. This study compared the efficacy and tolerability between gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM) as first-line chemotherapy in patients with advanced pancreatic cancer. Methods: We collected data ofpatients if they met the following criteria: histologically or cytologically confirmed ductal adenocarcinoma of the pancreas; unresectable/metastatic disease; treated with one of GEM, GEM-X, and GEM-T as first-line treatment; measurable or evaluable lesion; age more than 18 years; Eastern Cooperative Oncology Group performance status 0, 1, or 2; and adequate hematologic, hepatic, and renal function before first-line chemotherapy. Response rate, progression-free survival (PFS), overall survival (OS), and toxicity were evaluated. Results: Between January 2007 and November 2011, a total of 127 patients received one of GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved the objective response rate (21.2% vs. 12.7% and 15.9%), progression-free survival (8.9 vs. 5.2 and 3.9 months; p < 0.001) and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. The incidence of adverse events was not significantly different among groups. Conclusions: GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in locally advanced and metastatic pancreatic cancers. It is worthy to further investigate which agent has clinical advantage as combination drug with gemcitabine in pancreatic cancer and to explore predictive markers for each regimen leading to personalize anti-cancer treatment.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 356-356 ◽  
Author(s):  
Kei Saito ◽  
Masato Ozaka ◽  
Ryo Kanata ◽  
Ikuhiro Yamada ◽  
Takashi Sasaki ◽  
...  

356 Background: FOLFIRINOX is the first-line chemotherapy for patients with unresectable pancreatic cancer and yielded a longer overall survival, a superior progression-free survival, a higher objective response rate compared with gemcitabine alone. Maximum tumor shrinkage of primary site (MTSP) was associated with the survival outcome in colon cancer. However the data of tumor shrinkage in pancreatic cancer has not been well-documented. Therefore, we re-evaluated FOLFIRINOX focusing on the tumor shrinkage of primary site. We also assessed impact of tumor shrinkage on survival of unresectable pancreatic cancer. Methods: Medical records were retrospectively reviewed for consecutive patients receiving FOLFIRINOX as the first-line chemotherapy between January and December 2014. Response was evaluated by CT scan every 2 or 3 months until the end of treatment. We analyzed patients’ characteristics and rate of MTSP related to overall survival (OS) and progression free survival (PFS). Results: Thirty one patients were analyzed: median age of 62, male gender in 64.5%, performance status of 0 in 90.3%, metastatic cancer in 58.1%, the head of cancer in 41.9%, the UGT1A1 wild type in 48.4%, overall response rate in 25.8%. PFS was 7.7 months (95%CI: 6.57-9.6). Rate of MTSP were 18.8% (locally 18.8%, metastatic 18.1%) and rate of GRs/non-GRs/non-R (GRs (Good responders) were defined as patients whose MTSP were more than 20% and non-GRs (non-Good responders) were less than 20%) were 45.2%/35.5%/19.3%. PFS was 9.0(95%CI, 6.7- ) months in GRs, compared with 6.9(95%CI, 3.6-10.2) months in non-GRs (p = 0.15). Conclusions: MTSP by FOLFIRINOX could not affect PFS of pancreatic cancer.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 631-631
Author(s):  
S.P. Somashekhar ◽  
Amit Rauthan ◽  
Ashwin K Rajgopal ◽  
Rohit Kumar C

631 Background: Early tumor shrinkage (ETS) and depth of response (DoR) predict overall survival (OS) in first-line chemotherapy + anti-EGFR monoclonal antibodies in KRAS wild-type metastatic colorectal cancer (mCRC). This association and the predictive accuracy of response measurements were investigated in the first-line setting for FOLFOX/FOLFIRI plus cetuximab. Methods: We performed a study of FOLFOX/FOLFIRI plus cetuximab as first-line treatment in Indian patients with KRAS wild-type mCRC. The primary endpoint was response rate (RR), and secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Radiologic assessments at week 8 were used to calculate the relative change in the sum of the longest diameters of the target lesions. Cox regression models analysis investigated associations between ETS and overall survival (OS) and progression-free survival (PFS). Results: Sixty (78.9 %) of 76 patients had ETS, which was associated with prolonged PFS and OS. Both ETS and DoR were able to predict survival as accurately as RECIST response. Both ETS and DoR were associated with PFS and OS at the univariate analyses and in the multivariate models stratified for other prognostic variables. In the study patients, the RR, median PFS, and OS were 68.4 %, 13.1 months, and 30.6 months, respectively. Median DpR was 52%. The DpR correlated with OS as well as PFS. FOLFOX plus cetuximab was active as a first-line, with no major toxicities. Conclusions: Our prospective evaluation of chronological tumor shrinkage showed that ETS and DpR correlate with outcomes in patients with KRAS wild-type mCRC who receive cetuximab-based chemotherapy. Achieving rapid and deep tumor shrinkage consistently delays tumor progression and prolongs survival in patients treated with first-line chemotherapy plus cetuximab. ETS is a promising and valuable end point for clinical trials’ design deserving further investigation.


2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hisao Imai ◽  
Keita Mori ◽  
Nodoka Watase ◽  
Sakae Fujimoto ◽  
Kyoichi Kaira ◽  
...  

Background. The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small-cell lung cancer (SCLC). Therefore, by using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) or postprogression survival (PPS) and OS after first-line chemotherapies in patients with extensive disease-SCLC (ED-SCLC) treated with carboplatin plus etoposide.Methods. Between July 1998 and December 2014, we analyzed 63 cases of patients with ED-SCLC who were treated with carboplatin and etoposide as first-line chemotherapy. The relationships of PFS and PPS with OS were analyzed at the individual level.Results. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r=0.90,p<0.05, andR2=0.71) and PFS was moderately correlated with OS (r=0.72,p<0.05, andR2=0.62). Type of relapse (refractory/sensitive) and the number of regimens administered after disease progression after the first-line chemotherapy were both significantly associated with PPS (p<0.05).Conclusions. PPS has a stronger relationship with OS than does PFS in ED-SCLC patients who have received first-line chemotherapy. These results suggest that treatments administered after first-line chemotherapy affect the OS of ED-SCLC patients treated with carboplatin plus etoposide.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Kitadai ◽  
Tatsunori Shimoi ◽  
Kazuki Sudo ◽  
Emi Noguchi ◽  
Yusuke Nagata ◽  
...  

Abstract Background Standard treatment for malignant peritoneal mesothelioma has not been established, and systemic chemotherapy is administered according to malignant pleural mesothelioma. We previously reported the efficacy of cisplatin plus pemetrexed as first-line chemotherapy; however, the efficacy of second-line chemotherapy remains unknown. Methods We retrospectively evaluated patients with malignant peritoneal mesothelioma who started first-line systemic chemotherapy with platinum plus pemetrexed between March 2007 and February 2019 at the National Cancer Center Hospital. Patients who received second-line chemotherapy after failure of platinum plus pemetrexed were identified. We evaluated the efficacy of first- and second-line chemotherapy, and explored the prognostic factors. Survival outcomes were estimated using the Kaplan–Meier method, and between-group differences were compared using the log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models. Results A total of 54 and 26 patients received platinum plus pemetrexed as first- and second-line chemotherapy, respectively (gemcitabine in 12 patients; taxane, six; nivolumab, three; and others, five). In all patients, the median overall survival and progression-free survival after first-line chemotherapy were 16.6 and 7.3 months, respectively. Among patients who received second-line chemotherapy, the median overall survival, progression-free survival, and second-line overall survival were 16.9, 3.2, and 9.9 months, respectively. Patients who received ≥6 cycles of platinum plus pemetrexed as first-line chemotherapy had longer overall survival after second-line chemotherapy than those who did not (hazard ratio, 0.23; 95% confidence interval: 0.06–0.82; p = 0.02). Conclusions Second-line chemotherapy may be an option for refractory malignant peritoneal mesothelioma, especially in patients who have completed 6 cycles of platinum plus pemetrexed as first-line chemotherapy.


2021 ◽  
Vol 12 ◽  
Author(s):  
Elisa Lenotti ◽  
Andrea Alberti ◽  
Francesca Spada ◽  
Vito Amoroso ◽  
Patrick Maisonneuve ◽  
...  

ObjectiveAntiproliferative activity of somatostatin analogs (SSAs) has been demonstrated in digestive neuroendocrine tumors (NETs), but few data have been published in patients with pulmonary NETs. We therefore conducted a retrospective study to provide additional data on the outcome of patients with metastatic lung NETs submitted to front line SSAs.Research Design and MethodsPatients with metastatic lung NET treated with first line SSA-monotherapy (octreotide or lanreotide) in two different reference Institutions were reviewed. Outcome measures were progression-free survival (PFS) overall survival (OS), overall response rate and safety. We also explored prognostic factors associated with PFS.MethodsThe outcome of consecutive patients (pts) with metastatic lung NETs, who underwent first-line treatment with SSAs, recruited from 2014 on 2019 in two Italian reference Institutions, was retrospectively evaluated.ResultsThirty-one patients entered the study: 14 (45.2%) with typical and 17 (54.8%) atypical carcinoid. Six patients (19.4%) had a carcinoid syndrome. 60.0% of patients had Ki-67 ≤ 10%. Two (6.5%) patients obtained a partial response, 24 (77.4%) disease stabilization while 5 (16.1%) had progressive disease. Median progression free survival (PFS) was 28.6 months, median overall survival (OS) was not attained. Ki-67 ≤ 10%, typical carcinoid histotype and non-functioning disease, were associated with a non-significant PFS prolongation. PFS in patients with atypical carcinoids and in those with Ki-67 &gt;10% was greater than 19 months.ConclusionsThe long PFS and OS obtained in this case series suggest that SSAs could be effective as first line approach in the management of patients with progressive, metastatic pulmonary NET.


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