PACIFIC: An Ocean of Hope in Patients With Stage III Unresectable Non–Small Cell Lung Cancer
Authors: Dipesh Uprety, David E. Marinier
Journal: Journal of the National Comprehensive Cancer Network (2018)

Lung cancer is the leading cause of cancer-related death worldwide. 1In 2012, an estimated 1.8 million new lung cancer cases were diagnosed. 1Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases, and approximately 40% of these patients present with stage III disease. 2 For patients whose disease is deemed unresectable, concurrent chemoradiation (CRT) is the standard of care.A phase II study (SWOG 9010) conducted by Albain et al 3 was the first landmark trial showing the feasibility of the cisplatin/etoposide combination with radiotherapy in patients with locally advanced NSCLC.Concurrent CRT treatment is superior to a sequential approach, but has the disadvantage of increased toxicity. 4p to 10% of patients receiving concurrent CRT will have early treatment-related mortality. 5Despite this intense therapy with curative intent, median survival is approximately 18 to 28 months and only approximately 15% of these patients are alive at 5 years. 4,5Unfortunately, no major advances have been made in this group of patients for many years.The use of a higher dose of radiation does not improve survival and is associated with inferior outcomes.Additionally, no role for targeted therapy with CRT has been proven.Antonia et al 6 recently reported the results of the phase III PACIFIC trial, which evaluated the role of durvalumab (a selective monoclonal antibody against programmed death-ligand 1 [PD-L1]) as consolidation therapy in patients with stage III, locally advanced, unresectable NSCLC that had not progressed after concurrent CRT therapy.The study used a fixed time frame for randomization, and immunotherapy was started without significant delay.A total of 709 patients were randomly assigned in a 2:1 fashion to receive either durvalumab (n=473) or placebo (n=236) every 2 weeks for up to 12 months.The study revealed significant improvement in progression-free survival (PFS) with durvalumab: 16.8 months (95% CI, 13.0-18.1)versus 5.6 months (95% CI, 4.6-7.8) in the placebo arm.The benefit was seen irrespective of sex, smoking status, PD-L1 expression, and tumor histology type.Additionally, the development of new lesions was lower in the durvalumab arm (20.4% vs 32.1%).The brain is a common metastatic site for NSCLC, and has been historically associated with decreased survival and poor quality of life.The rate of new brain lesions in the PACIFIC trial was almost halved with durvalumab (5.5% vs 11.0%).Although the overall survival (OS) data are yet to mature, a PFS benefit of almost a year and a significant decrease in the occurrence of new lesions, including brain lesions, provide reasons to consider durvalumab as a new standard of care.Various platinum-based chemotherapy regimens can be used for concurrent CRT, including cisplatin/etoposide, carboplatin/paclitaxel, cisplatin/vinblastine, and, for nonsquamous pathology, carboplatin or cisplatin with pemetrexed. 7The carboplatin/ paclitaxel regimen is given weekly with radiation therapy, at carboplatin dosed to an area under the curve (AUC) of 2 and paclitaxel dosed at 45 to 50 mg/m 2 , followed by 2 additional cycles of full-dose chemotherapy (carboplatin, AUC=6 and paclitaxel, 200 mg/m 2 ). 8Should treating oncologists therefore omit these 2 additional full-dose chemotherapy cycles when using this regimen?The authors of the PACIFIC trial do not comment on this issue.Also, can these data be extrapolated to the subset of pa-