P018 Afatinib Named Patient Use Program in Advanced NSCLC with Progression on Prior Therapy: Experience from Asian Centers

Abstract

Background: Cyber Knife robotic stereotactic radiosurgery is minimally invasive tumor treatment modality that can deliver high precision radiotherapy to any part of the body with minimal exposure to adjacent and surrounding vital organs and is used to treat oligometastasis of the lung from primary breast cancer patients. In the modern high precision treatment delivery, utmost care should be taken for motion management of tumor targets. The Objective of this study was to investigate the accuracy and efficacy of Cyber knife in the treatment of lung metastasis from breast cancer using fuducial free respiratory tracking system using cyberknife stereotactic radiosurgery. Method: We examined toxicity and local control rate with fiducial-free CyberKnife stereotactic body radiation therapy (SBRT) for lung metastases from 20 breast cancer patients. All patients had favorable performance status (ECOG 0e2), oligometastatic disease. Total of 56 Lungs lesions were treated with a prescribed dose of 30e35 Gy delivered in five fractions to the planning target volume (PTV) using the CyberKnife with X-sight lung tracking. A median 30 Gy (IQR, 30e35 Gy) dose was delivered to a median prescription isodose line of 70% (IQR, 65e77%) to 20 patients with a total median follow up of 34 months. Results: The toxicity and local control rates were favourable and 1-and 2-year local control estimates were 87% and 73%, respectively. Two of the five local failures were infield in patients who had received irradiation to the gross tumor volume and remaining 3 were in patients who had received irradiation to clinical target volume. No local failures were identified beyond 21 months of therapy. There was no lung, oesophageal or spinal cord toxicity noted in the above patients. Conclusion: Initial evaluation with fiducial free based respiratory tracking system using five-fraction CyberKnife SBRT is a promising treatment option for lung metastasis from breast cancer patients, demonstrating encouraging local control rates with no toxicity. a dose escalation study for the pheripheral lung metastasis from breast cancers is being planned.Background: Recent randomized phase III trials (ALTA-1L and ALEX) reported the robust efficacy of next-generation anaplastic lymphoma kinase (ALK) inhibitors (brigatinib and alectinib) for the first-line treatment of patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). However, there is no head-to-head comparison of brigatinib vs. alectinib. In this study, we aimed to explore the optimal choice of ALK inhibitors treatment for advanced ALK-Positive NSCLC. Method: We performed an indirect comparison of ALTA-1L and ALEX to compared therapeutic efficacy and adverse event (AE) between brigatinib and alectinib as the first-line treatment of advanced ALK-Positive NSCLC. The clinical outcomes were progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and AE. Hazard ratio (HR, for PFS and OS) / risk ratio (RR, for ORR and AE) and its 95% confidence interval (CI) were extracted. R...

Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review

“…Studies that reported on the prognostic impact of Exon 20ins varied significantly with regards to the genotypes compared, line and type of therapy received, and patient ethnicity. The majority of studies were retrospective chart reviews (n = 10), with three exceptions: one post-hoc analysis of trial data (LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6) [ 21 ] and two prospective registries [ 23 , 24 ]. Most studies were conducted in Asia (n = 8), with the remainder in the US (n = 3), Europe (n = 1), and Latin America (n = 1).…”

“…No comparative studies were identified, but rather, nine single-arm phase I/II trials (range 11-115 patients) [40, 42, 43, 45-47, 49, 52, 53] two prospective cohort studies (29 and 35 patients) [23,29,39], two pooled analyses of clinical trials (21 and 23 patients) [21,48], and 22 retrospective observational studies (range 15-165 patients). Half of the studies (n = 16) reported on subgroups or select cohorts of patients with Exon 20ins from studies with broader PLOS ONE PLOS ONE study populations, and half were conducted in Asia (n = 14), followed by the US (n = 8).…”

“…Median PFS and ORR were also more favorable for patients with Exon 20ins receiving chemotherapy (median PFS: 3.4-6.9 months for chemotherapy-based regimens [range 10-105 patients] [29,32,33,37,38] Second-or later-line clinical outcomes. Sixteen studies (reported across 21 publications) reported the clinical efficacy/effectiveness and safety of various subsequent-line treatment regimens in patients with Exon 20ins, but based on very limited sample sizes (range 11-165 patients) [10,23,24,29,30,37,[39][40][41][42][43][44][45][46][47][48][49][50][51][52][53].…”

Experience from Asian centers in a named-patient-use program for afatinib in patients with advanced non-small-cell lung cancer who had progressed following prior therapies, including patients with uncommon EGFR mutations

“…The ORR in the current analysis was 43% (3/7 patients), compared with 30% (8/27 patients) in the global NPU analysis [4]. The difference in median TTF between patients with G719X, L861Q, or S768I mutations in the Asian subgroup and the global NPU program may have been particularly influenced by the median of 21.1 months among patients from Taiwan [12], who were not included in the global NPU analysis [4]. However, the prolonged outcomes reported here for patients with G719X, L861Q, or S768I mutations are in agreement with data from the LUX-Lung 2, 3, and 6 studies; for patients with G719X, L861Q or S768I, ORR ranged from 56 to 100%, median PFS 8-15 months, and median OS was 17 months-not estimated.…”

“…This is an important finding as, without evidence, it cannot be assumed that patients from Asia respond similarly to those from other regions. However, median TTF for EGFR mutation-positive [12]. When the NPU program began, investigators/clinicians in Taiwan had already gained experience in the use of afatinib, through their involvement in phase I and II trials.…”