ABSTRACT
Lalatendu Moharana The Anaplastic lymphoma kinase inhibitors (ALKi) represent the standard of care for metastatic non-small cell lung cancer (NSCLC) patients with EML4-ALK rearrangements. Various ALKi agents are available; however, not all eligible patients receive treatment with them due to various reasons. Given the limited real-world data available in our country, we aimed to assess treatment outcomes through a multicenter collaboration. This retrospective, multi-institutional study was conducted under the Network of Oncology Clinical Trials India and included a total of 67 ALK-positive metastatic lung cancer patients from 10 institutes across India, with a median follow-up of 23 months. In the first line setting, the objective response rate (ORR) with ALKi was 63.6% (crizotinib: 60.7%, ceritinib: 70%, alectinib: 66.6%, p = 0.508), while with chemotherapy, it was 26.1%. The median progression-free survival (mPFS) for the first line ALKi group was significantly higher than that for chemotherapy (19 vs. 9 months, p = 0.00, hazard ratio [HR] = 0.30, 95% confidence interval [CI]: 0.17-0.54). The mPFS for crizotinib, alectinib, and ceritinib was 17, 22, and 19 months, respectively ( p = 0.48). Patients who received ALKi upfront or after 1 to 3 cycles of chemotherapy or after 4 or more cycles of chemotherapy had mPFS of 16, 22, and 23 months, respectively ( p = 0.47). ALKi showed superior mPFS compared to chemotherapy in the second line (14 vs. 5 months; p = 0.002) and the third line (20 vs. 4 months; p = 0.009). The median overall survival (OS) was significantly better in patients who received ALKi in any line of therapy (44 vs. 14 months, p < 0.001, HR = 0.10, 95% CI: 0.04-0.23). Brain progression was higher among those who did not receive ALKi (69.2 vs. 31.5%). In conclusion, the use of ALKi as first line treatment for ALK-positive metastatic NSCLC patients resulted in improved PFS. PFS and ORR did not significantly differ between patients who received ALKi upfront or after initiating chemotherapy. Notably, patients who received ALKi in second or later lines demonstrated significantly better outcomes compared to those receiving chemotherapy. The use of ALKi in any line of therapy was associated with significantly prolonged OS.
ABSTRACT
OBJECTIVE: To investigate the safety and efficacy of goat lung surfactant extract (GLSE) compared with bovine surfactant extract (beractant; Survanta®, AbbVie, USA) for the treatment of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: We conducted a double-blind, non-inferiority, randomized trial in seven Indian centers between June 22, 2016 and January 11, 2018. Preterm neonates of 26 to 32 weeks gestation with clinical diagnosis of RDS were randomized to receive either GLSE or beractant. Repeat dose, if required, was open-label beractant in both the groups. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age (PMA). Interim analyses were done by an independent data and safety monitoring board (DSMB). RESULT: After the first interim analyses on 5% enrolment, the "need for repeat dose(s) of surfactant" was added as an additional primary outcome and enrolment restricted to intramural births at five of the seven participating centers. Following second interim analysis after 98 (10% of 900 planned) neonates were enroled, DSMB recommended closure of study in view of inferior efficacy of GLSE in comparison to beractant. There was no significant difference in the primary outcome of death or BPD between GLSE group (n = 52) and beractant group (n = 46) (50.0 vs. 39.1%; OR 1.5; 95% CI 0.7-3.5; p = 0.28). The need for repeat dose of surfactant was significantly higher in GLSE group (65.4 vs. 17.4%; OR 9.0; 95% CI 3.5-23.3; p < 0.001). CONCLUSIONS: Goat lung surfactant was less efficacious than beractant (Survanta®) for treatment of RDS in preterm infants. Reasons to ascertain inferior efficacy of goat lung surfactant requires investigation and possible mitigating strategies in order to develop a low-cost and effective surfactant.
