Adjuvant Gefitinib May Extend DFS in NSCLC With EGFR-Activating Mutations

Adjuvant Gefitinib May Extend DFS in NSCLC With EGFR-Activating Mutations

Dr. Yi-Long Wu presents Abstract 8500.
The EGFR tyrosine-kinase inhibitor (TKI) gefitinib appears to offer a disease-free survival (DFS) benefit over vinorelbine/cisplatin as adjuvant therapy in patients with non–small cell lung cancer (NSCLC) with EGFR-activating mutations, according to results of the randomized, phase III ADJUVANT trial (CTONG 1104) presented by Yi-Long Wu, MD, of the Guangdong General Hospital, in China, on June 5 (Abstract 8500).

The trial enrolled 222 patients with stage II to IIIA (N1-N2) completely resected NSCLC with EGFR-activating mutations and randomly assigned them to receive adjuvant therapy with gefitinib (111 patients) or vinorelbine/cisplatin (111 patients).

Efficacy Outcomes

In an intention-to-treat analysis, median DFS was significantly longer in the gefitinib arm than the chemotherapy arm, at 28.7 months and 18.0 months, respectively (hazard ratio for recurrence 0.60, 95% CI [0.42, 0.87]; p = 0.005). The 3-year DFS rates were 34% and 27%, respectively. Outcomes were similar among all subgroups reported, including sex, smoking status, type of EGFR mutation, lymph node status (N1 vs. N2), and histology.

Dr. Suresh Senan discusses Abstract 8500.
Overall survival (OS) data are not yet available, and multiple experts said that this will be a crucial endpoint. “The [DFS] curves begin to come together a bit after 3 years, so it will be very important to hear what happens later in terms of survival,” 2017–2018 ASCO President Bruce E. Johnson, MD, FASCO, of the Dana-Farber Cancer Institute, said during a Press Briefing.

Another point discussed at the session was the high rate of treatment refusals in the chemotherapy arm—23 patients (21%) compared with five patients (5%) in the gefitinib arm. These chemotherapy refusals were included in the intention-to-treat analysis, a point that one attendee noted could have affected the results. A per-protocol analysis was not reported.

Safety Outcomes

Gefitinib was also better tolerated than chemotherapy, with less neutropenia, anemia, leukopenia, myelosuppression, nausea, vomiting, and anorexia. Although gefitinib was associated with more rash, liver enzyme elevations, and diarrhea, few of these adverse events were severe. Grade 3 or higher adverse events were reported in 12% of patients receiving gefitinib and 48% of those receiving chemotherapy. Gefitinib was also associated with significant improvements in health-related quality of life compared with chemotherapy.

]Dr. Wu concluded that adjuvant gefitinib can delay the recurrence of intermediate-stage lung cancer after surgery and “could be the preferred approach in patients with resected N1/N2 EGFR-mutant NSCLC.”

In his discussion of the abstract, Suresh Senan, MRCP, FRCR, PhD, of the VU University Medical Center, in the Netherlands, noted that adjuvant chemotherapy is the standard of care in intermediate-stage lung cancer, but it is associated with only a modest survival benefit. Moreover, no biomarkers have been identified to select patients more likely to benefit from adjuvant chemotherapy.

Given the demonstrated activity of EGFR TKIs in the treatment of EGFR mutation–positive metastatic NSCLC, there has been great interest in the potential role of EGFR TKIs in the adjuvant setting. In previous trials, including BR19 and RADIANT, EGFR TKIs appeared to provide limited benefit as adjuvant treatment in patients with resected NSCLC. However, Dr. Senan pointed out that the RADIANT trial did show a significant benefit with erlotinib over placebo in a subset of patients with EGFR mutations.

In comparison to these prior trials, which Dr. Senan explained assigned patients to receive an EGFR TKI or placebo after adjuvant chemotherapy, the current ADJUVANT trial was a head-to-head trial directly comparing a TKI with chemotherapy in the adjuvant setting. He added that more details would be helpful for interpreting the results, including the use of FDG-PET, N2 subtypes, and treatment failure patterns. Also important to consider, he said, are patient preferences and differences in cost, which are substantial with an estimated cost of $447 for chemotherapy and $184,879 for gefitinib.  

–Melinda Tanzola, PhD

Note from Dr. John Sweetenham, ASCO Daily News Editor in Chief: This study shows an improvement in 3-year DFS from 27% to 34% for adjuvant gefitinib compared with the current standard of care chemotherapy, but at an additional cost per patient of more than $184,000. The absence of a per-protocol analysis means that the real improvement in DFS may be higher than seen in this study, but since the DFS curves are converging and there are no OS data yet available, it is questionable whether this represents improved value for the adjuvant therapy of intermediate-stage NSCLC.