All EGFR mutations are (not) created equal: focus on uncommon EGFR mutations.

PURPOSE: Most common EGFR mutations in NSCLC include del19 and exon 21 L858R. Approximately 10% of patients have uncommon EGFR mutations (indels, missense mutations involving G719, L861 and S768 codons, and exon 20 insertions) that do not respond to TKIs. METHODS: Of 490 EGFR mutated NSCLC samples, 60 cases harboring uncommon/compound EGFR mutations were reviewed retrospectively, and 44 were included for survival analysis. RESULTS: Sixty (12.2%) patients with a median age of 63 years (25-84 years) had uncommon/compound EGFR mutations. Majority had no history of smoking (52; 86.7%). Most common major uncommon mutations (G719X in exon 18, L861Q in exon 21 and S768I in exon 20) were identified in 19 (31.7%) patients. 17 (28.3%) cases demonstrated exon 20 insertions. De novo T790M was observed in 7 (11.7%) cases and 9 cases exhibited compound/dual mutations. Among the 12 patients who received first-line EGFR TKI, 7 received afatinib. Median progression-free survival of patients following first-line afatinib was 8.13 months, irrespective of mutation type exhibited. Overall response rate to first-line afatinib therapy was 57.1%. CONCLUSION: The current study highlighted that rare/dual EGFR mutations are heterogeneous with distinct clinical features in a large Indian cohort of EGFR mutated patients with NSCLC.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. @*Materials and Methods@#Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. @*Results@#At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. @*Conclusion@#Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Radial endobronchial ultrasound for the diagnosis of bronchoscopically invisible lesions: First case series from India.

BACKGROUND: A peripheral, bronchoscopically invisible pulmonary lesion is a diagnostic challenge. Transthoracic needle aspiration has long been the investigation of choice but runs the risk of pneumothorax (up to 44%). Newer technologies like radial endobronchial ultrasound (R-EBUS) offer a safer approach. We present our results of R-EBUS in the diagnosis of bronchoscopically invisible lesions. This is the first large case series from India. AIMS: (1) To determine the yield of R-EBUS for the diagnosis of bronchoscopically invisible lesions. (2) To compare the yields of forceps versus cryobiopsies in the diagnosis of these lesions. SETTING: Tertiary care cancer center. DESIGN: Prospective study. METHODS: Consecutive patients presenting between January and October 2015 with bronchoscopically invisible peripheral pulmonary lesions were included. R-EBUS was used to localize and sample the lesion and the yields were analyzed. Yields of cryo and forceps biopsy were compared where both methods had been used. Data were analyzed using SPSS version 22. RESULTS: A definite diagnosis obtained in 67.3% (37/55) patients with no major complications. No significant difference was found in yield between: (1) small (<3 cm) and large (>3 cm) lesions: (46.2% versus 78.6%, P = 0.38). (2) central and adjacent lesions: 61.5% versus 70%. (3) forceps and cryobiopsy (n = 28, 75% versus 67.9% P = 0.562). CONCLUSIONS: R-EBUS is a safe procedure in our setting and its yield is comparable to that reported in literature. The yield of central and adjacent lesions and forceps or cryobiopsy appears similar. Further refinements in the technique could improve yield.

Efficacy and toxicity profile of maintenance pemetrexed in patients with stage IV adenocarcinoma lung in Indian population.

CONTEXT: Lung cancer has been the most common cancer in the world for several decades. Pemetrexed is recommended as an option for the maintenance treatment in metastatic adenocarcinoma lung, if disease has not progressed immediately following platinum-based chemotherapy. AIMS: To study efficacy and toxicity profile of pemetrexed as a maintenance chemotherapeutic agent in patients with stage IV adenocarcinoma lung, not progressing after first line chemotherapy. Settings and Design: This was an observational, prospective. We enrolled patients with stage IV adenocarcinoma lung who has not progressed on first line chemotherapy, from September 2013 to August 2014 at a tertiary care cancer institute in North India. MATERIALS AND METHODS: In all, 108 patients with stage IV adenocarcinoma lung were started on induction pemetrexed/platinum chemotherapy. 60 patients with no disease progression & ECOG PS 0-2 were started on Pemetrexed maintenance. Progression free survival (PFS) and toxicity profile were recorded. RESULTS: The mean number of maintenance cycles was 8.3 (range 2-28). 13 (21.6%) patients took >10 maintenance cycles. Pemetrexed maintenance therapy resulted in progression free survival (PFS) of 5.4 months. PFS on pemetrexed was consistent for all patient subgroups, including induction response: complete/partial responders (n-31) and stable disease (n-29). 14 patients had grade III/IV adverse events with anemia being the most common in 3/60 patients (5%). 3 patients (5%) developed renal dysfunction out of which 1 was grade III. CONCLUSIONS: Pemetrexed continuation maintenance chemotherapy is active and well tolerated. Pemetrexed maintenance should be considered in patients with advanced adenocarcinoma lung patients who have not progressed on completion of induction chemotherapy.

Malignant myelomatous pleural effusion-Is onset of effusion a new prognostic factor?

Malignant pleural effusion in myeloma (MMPE) is a rare terminal event; with a median survival is four months. All the patients usually have multiple poor prognostic factors and none of them (like beta 2-microglobulin, karyotype, Stage of disease, C-reactive protein etc.) correctly predicts the survival. We are reporting a series of five cases and evaluated the factors influencing the overall survival. All of our patients had a very good response to treatment and had a better survival compared to the reported cases so far. After reviewing the literature carefully we found that timing of development of pleural effusion is probably the most important prognostic factor. Those who develop effusion after some time lag form the initial treatment, will have a poor survival (median four months) compared to those who had effusion at the start of the disease.