Updated survival outcomes of NEJ005/TCOG0902: a randomised phase II study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations

Abstract

BackgroundThe North-East Japan Study Group (NEJ) 005/Tokyo Cooperative Oncology Group (TCOG) 0902 study has reported that first-line concurrent and sequential alternating combination therapies of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant non-small cell lung cancer. However, overall survival (OS) data were insufficient in the primary report because of the lack of death events.Patients and methodsProgression-free survival (PFS) and OS were re-evaluated at the final data cut-off point (March 2017) for the entire population (n=80).ResultsAt the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the concurrent regimen and 15.3 months for the sequential alternating regimen (P=0.13). Median OS was 41.9 and 30.7 months, respectively (P=0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; P=0.34). Patients with Del19 tumours displayed relatively better OS (median: 45.3 vs 33.3 months, respectively) than those with L858R (31.4 vs 28.9 months, respectively). No severe adverse events, including interstitial lung disease, occurred in the period since the primary report.ConclusionsThis updated analysis confirms that PFS is improved with first-line combination therapy compared with gefitinib monotherapy and that the concurrent regimen, in particular, offers an OS benefit of 42 months in the EGFR-mutated setting. Our ongoing NEJ009 study will clarify whether this combination strategy can be incorporated into routine clinical practice.Trial registration numberUMIN C000002789, Post-results.

Combination of icotinib and chemotherapy as first-line treatment for advanced lung adenocarcinoma in patients with sensitive EGFR mutations: A randomized controlled study

“…In the present study, the OS of the combination group was 36.0 months, which was shorter than that in the NEJ005 study (41.9 months) [10]. This difference might be related to the different maintenance treatment regimens applied.…”

“…In the present prospective, randomized, controlled trial, we found that PFS in the combination group was significantly longer than that in the icotinib group, and moreover, the ORR and DCR in the combination group were significantly higher than those in the icotinib group. The NEJ005 study compared a concurrent regimen and a sequential alternating regimen for the combination of gefitinib and chemotherapy [10,11]. Our in vitro studies suggested that the sequential administration of pemetrexed followed by icotinib exerted a synergistic effect on EGFR-mutant human lung adenocarcinoma cell lines [16], and that the volume and weight of tumor xenografts in the sequential pemetrexed followed by icotinib group were significantly smaller than sequential icotinib followed by pemetrexed group [14].…”

“…The strategy was also supported by FASTACT-2 and several other clinical researches [21][22][23]. However, the NEJ005 study showed improved OS for the concurrent schedule of gefitinib and chemotherapy [10,11]. Clinical studies might be affected by a variety of factors, which resulted in the inconsistent results with in vitro studies.…”

“…For example, Han et al found that gefitinib given together with chemotherapy resulted in a longer PFS than either chemotherapy or gefitinib alone [9]. Moreover, in patients with advanced lung adenocarcinoma and sensitive EGFR mutations, the NEJ005 study found that both PFS and OS were extended by concurrent combined treatment with gefitinib and chemotherapy [10,11] compared with the PFS and OS achieved with TKI monotherapy [12].…”

PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison

“…72.4%, HR 0.6; 95% CI: 0.41–0.89, p = 0.005), whether single agent Pembrolizumab is enough for PD‐L1 high expressed patients or whether extra chemotherapy would have additional benefit remains a popular topic. We might refer to the result of NEJ009, which was the first phase III clinical trial that evaluated the combination of EGFR‐TKI and chemotherapy compared to TKI alone for EGFR mutated patients as first‐line therapy . The results highlighted the combination strategy as an optimal; it would prolong not only the PFS time (20.9 m vs .…”