Anti PD-L1 Agent Shows Durable Response in Lung Cancer
Virginia Powers, Ph.D.
Clinical benefit and durable response was seen when durvalumab was used in the second-line and beyond for patients who were heavily pretreated with locally advanced or metastatic non-small cell lung cancer (NSCLC), according to findings from the 17th World Lung Cancer Conference in Vienna.
While PD-L1 expression levels are not considered to be a reliable biomarker for response to immunotherapeutic agents, response to durvalumab in the phase 2 ATLANTIC trial did increase with higher PD-L1 expression.
The objective response rate (ORR) with durvalumab increased in line with PD-LI expression: In PD-L1 low or negative patients with PD-L1 expression on less than 25 percent of tumor cells, the ORR was 7.5 percent, and ORR was 16.4 percent in patients with PD-L1 expression over 25 percent. But the highest ORR of 30.9 percent was observed in patients with tumoral PD-L1 expression on at least 90 percent of tumor cells.
One-year overall survival (OS) rates were 48 percent in patients with PD-L1 at least 25 percent and 51 percent in patients with PD-L1 90 percent or more.
This response appeared to be durable, with a median duration of response (DoR) that was not reached (NR): ORR in the respective groups was 12.3 months, NR, and NR, where 18 of 21 responders remained progression-free at data cut-off.
“Results from this trial with durvalumab in a heavily pre-treated population, many of whom have had three or more prior treatment regimens, are encouraging and consistent with efficacy observed with other immunotherapy medicines in metastatic, relapsed NSCLC,” commented Marina Garassino M.D., of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan.
Garassino presented data from two of the three cohorts of patients participating in the single-arm, phase 2, global ATLANTIC trial of durvalumab: Patients in cohort 2 were divided into PD-L1 low expressers, with less than 25 percent PD-L1 expression on tumor cells, and PD-L1 high expressers with 25 percent or more tumoral PD-L1 expression, and patients in cohort 3 were PD-L1 high expressers with 90 percent or more on tumour cells. Cohort 2 had 265 patients and Cohort 3 contained 68 patients who were treated with durvalumab at 10 mg/kg intravenous every two weeks.
The ATLANTIC study initially enrolled all-comers and then restricted enrollment to patients with PD-L1 high tumors determined by membrane staining. The trial was conducted in patients with locally advanced or metastatic stage 3B–4 NSCLC and EGFR/ALK wild-type tumors. All patients were heavily pretreated. Sixty percent of patients in cohort 2 and 40 percent of patients in cohort 3 received three or more lines of treatment prior to durvalumab.
The primary endpoint was ORR by RECIST v1.1, and secondary endpoints included disease control rate (DCR), DoR, progression-free survival (PFS), OS, and safety.
Responses were consistent and similar in patients with squamous and non-squamous histology, according to Garassino.
In cohort 2, patients with low and high expression demonstrated DCR of 20.4 percent and 28.8 percent, respectively, and patients in cohort 3 with the highest expression showed DCR of 38.2 percent.
The median PFS was 1.9 months, 3.3 months and 2.4 months in cohort 2 low- and high-expressing patients, and in cohort 3, respectively. OS in the respective groups was 9.3 months, 20.9 months, and NR.
Durvalumab showed a manageable safety and tolerability profile; most adverse events (AEs) were low grade and resolved with treatment delay and/or immunosuppressive interventions. Grade 3 or higher treatment-related AEs occurred in 8.3 percent and 17.6 percent of cohort 2 and cohort 3 patients, respectively.
“There were few discontinuations due to treatment-related adverse events,” she commented. Treatment-related AEs leading to discontinuation occurred in 2.7 percent of patients.
“These results are consistent with other anti-PD-1/PD-L1 therapies in metastatic, relapsed NSCLC and support the ongoing development program of durvalumab,” commented Garassino. Durvalumab is currently undergoing testing in NSCLC with and without the CTLA-4 monoclonal antibody, tremelimumab, in the phase 3 MYSTIC; NEPTUNE; ARCTIC; and PACIFIC trials.