MA14.07 Phase I Expansion Cohort of Ramucirumab Plus Pembrolizumab in Advanced Treatment-Naïve Non-Small Cell Lung Cancer (JVDF)

Combination of Immunotherapy and Antiangiogenic Therapy in Cancer—a Rational Approach

“…It is also possible that these patients are simply at higher risk for cardiac events owing to tobacco exposure, for example, in the treatment-naive NSCLC cohort, in which 92% of the patients were former or current users of tobacco. 17 This high rate of tobacco exposure was also observed in the pretreated NSCLC cohort (96%), whereas a lower proportion was observed in the urothelial carcinoma and gastric/gastroesophageal junction cohorts (51% and 71%, respectively) in which no cardiac events were observed. 18 Furthermore, there was a slightly higher proportion of serious TRAEs of arterial thromboembolic events from the IMpower150 study in the chemotherapy arm containing both atezolizumab and bevacizumab.…”

“…The median treatment duration of ramucirumab was almost half as long as pembrolizumab (4.5 mo [interquartile range (IQR): 2.1-11.8] and 8.4 mo [IQR: 3.1-21.1], respectively). 17 In the pretreated NSCLC cohort with this combination, 15% of the patients also discontinued owing to TRAEs; however, the difference in median treatment duration between ramucirumab and pembrolizumab was not as striking (7.0 mo [IQR: 3.0-16.8] and 8.3 mo [IQR: 3.3-23.7], respectively). 18 There was a relatively high rate (15%) of arterial thromboembolic/cardiac events in this treatment-naive cohort despite the lower exposure to ramucirumab, which has previously been linked to decreased toxicity.…”

“…16 However, trials combining antiangiogenic therapy with immunotherapy in lung cancer are in early phases. In this issue, Herbst et al 17 report on cohort E of the phase 1 expansion JVDF study of combination of ramucirumab (anti-VEGFR2 monoclonal antibody) and pembrolizumab (PD-1 ICI) in PD-L1-positive (1%), treatment-naive advanced NSCLC. Patients received ramucirumab at 10 mg/kg and pembrolizumab at 200 mg intravenously every 21 days for up to 35 cycles.…”

“…19 This included two patients with grade 3/4 acute myocardial infarction, one grade 5 congestive heart failure, and additional events of a transient ischemic attack and greater than or equal to grade 3 pericardial effusion in one patient. 17 These cardiac events are of interest because the trial was not designed to attribute adverse events to individual study drugs and the time of onset of these events from start of study treatment is not described. It is well-established that antiangiogenic agents do have rare arterial thromboembolic risks such as myocardial infarction and stroke.…”

<p>Advanced Squamous Cell Carcinoma of the Lung: Current Treatment Approaches and the Role of Afatinib</p>

“…77 No differences in median OS were seen between the treatment arms in the overall PD-L1-positive population (14.8 versus 15.0 months), or in PD-L1negative patients (median 14.0 versus 12.5 months). 77 Early-phase studies are also exploring various combinations of approved and investigational agents, including pembrolizumab plus ramucirumab, 78 and novel agents such as anlotinib 79 and camrelizumab. 80 It has been suggested that radiotherapy in addition to chemotherapy plus immune checkpoint inhibitors, the current first-line standard of care for patients with advanced NSCLC, may further improve outcomes, but this strategy is yet to be tested in clinical trials.…”