Trends in response rate and survival in small-cell lung cancer patients between 1997 and 2017.

INTRODUCTION: Median survival of small-cell lung cancer (SCLC) patients is usually around 1 year. The advent of new drugs may have slightly improved their prognosis. We aimed to assess whether SCLC response to chemotherapy and survival had changed over time. METHODS: Consecutive SCLC patients were included at Grenoble University Hospital, France. We compared the patients' characteristics, response to chemotherapy and survival between 1997-2009 (period 1) and 2010-2017 (period 2). RESULTS: A total of 529 patients were identified, of whom 498 received a first line of chemotherapy and 279 a second line. The majority (n = 290, 58%) had extensive disease. The objective response rate (ORR) to first-line chemotherapy in metastatic patients was 63% in period 1 and 62% in period 2; the ORRs to second-line chemotherapy were 39% and 29%, respectively. Median overall survival from first-line chemotherapy was 13.2 months (interquartile range [IQR] 7.4-24.4) in period 1 and 11.2 months (IQR 7.1-21.2) in period 2. Mortality in these two periods did not differ significantly even after adjustment for prognostic factors (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.66-1.00). The factors independently associated with death were cardiovascular comorbidities (HR = 1.28 [95%CI 1.05-1.55]), liver comorbidities (HR = 1.31 [95%CI 1.03-1.65]), poor ECOG performance status (3-4vs. 0-1, HR = 2.45 [95%CI 1.83-3.30]) and extensive disease (HR = 2.69 [95%CI 2.18-3.33]). CONCLUSIONS: Since 1997, there has been no improvement in the survival or response rate to chemotherapy of SCLC patients. There is a desperate need for new approaches in this setting.

A Brief Report of Transformation From NSCLC to SCLC: Molecular and Therapeutic Characteristics.

INTRODUCTION: Histologic transformation from NSCLC to SCLC is a mechanism of resistance in EGFR-mutant tumors but is also occasionally observed in nonmutated NSCLC. METHODS: We performed a multicenter retrospective collection of cases presenting between 2005 and 2017. The objectives were to analyze survival data and to define epidemiologic, clinical, treatment and histomolecular characteristics at both the time of diagnosis of NSCLC and of SCLC. RESULTS: Forty-eight EGFR-mutant NSCLC and 13 non-EGFR-mutant cases were registered. Most EGFR-mutant tumors retained the same EGFR mutation after transformation. The median time to SCLC transformation was shorter in the EGFR-mutant group than in non-EFGR mutants (16 months versus 26 months (p = 0.01)). Both tumors were responsive to platinum etoposide regimens (45% partial response for the EGFR-mutant group versus 40% for non-EFGR mutants). The median overall survival rates were 28 months in the EGFR-mutant group versus 37 months in the non-EFGR-mutant group, respectively. After transformation, the median overall survival was 9 months in the non-EGFR-mutant group versus 10 months in the EGFR-mutant group. CONCLUSIONS: Transformation into SCLC seems to occur more quickly in EGFR mutated tumors; however, once the tumor is transformed its survival and response to treatment seems comparable to that of classical SCLC.

Operation and Chemotherapy: Prognostic Factors for Lung Cancer With One Synchronous Metastasis.

BACKGROUND: Stage IV non-small cell lung cancer (NSCLC) is considered incurable; however, some patients with only few metastases may benefit from treatment with a curative intent. We aimed to identify the prognostic factors for stage IV NSCLC with synchronous solitary M1. METHODS: A database constructed from our weekly multidisciplinary thoracic oncology meetings was retrospectively screened from 1993 to 2012. Consecutive patients with NSCLC stages I to IV were included. RESULTS: Of the 6,760 patients found, 4,832 patients were studied. Among the 1,592 patients (33%) with stage IV NSCLC, 109 (7%) had a synchronous solitary M1. Metastasis involved the brain in 64% of patients. Median overall survival was significantly longer in synchronous solitary M1 than in other stage IV (18.9 months, interquartile range [IQR]: 9.9 to 34.6 months versus 6.1 months, IQR: 2.3 to 13.7 months], respectively, p < 10-4). Among patients with synchronous solitary M1, 90 (83%) received a local treatment with curative intent at the primary and metastatic sites. Factors independently associated with survival were age older than 63 years (hazard ratio [HR] 1.63, 95% confidence interval [CI]: 1.01 to 2.63), Performance status of 3 or 4 (HR 7.91, 95% CI: 2.23 to 28.03), use of chemotherapy (HR 0.38, 95% CI: 0.23 to 0.64), and operation conducted at both sites (HR 0.35, 95% CI: 0.19 to 0.65). CONCLUSIONS: Synchronous solitary M1 treated with chemotherapy and operation at both sites resulted in better survival. Survival of NSCLC with synchronous solitary M1 was more similar to stage III than other stage IV NSCLCs. The eighth TNM classification takes this into account by distinguishing between stages M1b and M1c.

[Not Available]. / Nivolumab dans le traitement des CBNPC.

TREATMENT OF NSCLC WITH NIVOLUMAB: Chemotherapy with docetaxel has remained a cornerstone of second-line treatment for more than 15 years, but it is associated with an unfavorable safety profile. Recently, the results of 2 randomized phase III trials assessing nivolumab in lung cancer, Check-Mate-017 and Check- Mate-057, have deeply changed our current clinical practice and open the debate for further improvements in the clinical care of lung cancer. This paper explores the recent findings about nivolumab in the second-line setting and discusses future directions for nivolumab and other immune Oncology drugs.

Atypical response to erlotinib in a patient with metastatic lung adenocarcinoma: a case report.

INTRODUCTION: Tyrosine kinase inhibitors are widely prescribed in thoracic oncology and have excellent responses as a first-line treatment for locally advanced or metastatic lung cancer with epidermal growth factor receptor mutations. The side effects of tyrosine kinase inhibitors are mostly gastrointestinal and dermatological, and are usually resolved after symptomatic treatment. However, new complications have now arisen due to increased use of these drugs. Here we report a side effect of erlotinib that has not been described previously: that is, metastatic lung tumor nodules were transformed into cysts, which ruptured the pleura and were responsible for bilateral life-threatening pneumothorax. CASE PRESENTATION: We report the case of a 35-year-old Caucasian woman with metastatic adenocarcinoma and a deletion in epidermal growth factor receptor exon 19 (del E746-A750). She was treated with erlotinib for metastatic lung adenocarcinoma. Treatment with erlotinib resulted in the replacement of pulmonary tumor nodules with air-containing cysts. These cysts ruptured in the pleura causing a life-threatening bilateral pneumothorax. To the best of our knowledge, this tumor-cystic response after erlotinib therapy has not been previously described. CONCLUSIONS: Tyrosine kinase inhibitors are widely prescribed in thoracic oncology, and managing toxicities must be optimal in order to improve adherence. Transformation of pulmonary nodules into cysts must be known and clinicians should be aware of this potential complication, which can lead to life-threatening pneumothorax.