PFS improvement due to local therapy in oligometastatic NSCLC
Evidence suggests the existence of a ,limited metastatic’ NSCLC phenotype. However, the type of optimal treatment and the role of aggressive local therapy in these patients remain controversial. Gomez et al. presented the first prospective, randomised trial to address this question. Patients had stage IV disease without RECIST progression and a maximum of three metastases after front-line systemic therapy (FLST). Malignant pleural effusion was an exclusion criterion. FLST was defined as ≥ 4 cycles of platinum-doublet chemotherapy, ≥ 3 months of erlotinib, afatinib, or gefitinib therapy in case of EGFR mutation, or ≥ 3 months of crizotinib therapy for those with EML4-ALK fusion. The patients were randomised to either local consolidative therapy (LCT; surgery ± radiation to primary and metastases followed by standard maintenance or surveillance according to the physician’s choice) or no LCT (standard maintenance or surveillance according to the physician’s choice). PFS was defined as the primary outcome. Twenty-four patients were evaluable in each group.
Patients treated with LCT fared significantly better than the no-LCT group. Median PFS was 11.9 vs. 3.9 months, respectively (p = 0.005). At the same time, toxicity did not differ substantially. There were differences in patterns of failure that trended towards significance (p = 0.09) (Figure). Patients in the no-LCT arm experienced a comparatively higher proportion of locoregional-only and known (vs. new-site) failures, whereas those in the LCT arm showed comparatively higher percentages of metastatic-only and new failures. Both locoregional and metastatic failures were more common in the no-LCT Arm (29 % vs. 8 %). The time to new-site failure significantly favoured LCT (11.9 vs. 5.7 months; p = 0.0497), which suggests reductions in the metastatic spread.
Figure: Differences in the patterns of failure by treatment arm (local consolidative therapy or no local consolidative therapy)
In the entire cohort, two other factors associated with PFS were identified: patients with two to three metastases after FLST had worse outcomes than those with only one lesion (p = 0.043), as did those without EGFR/ ALK alterations as compared to patients who were either EGFR-positive or ALK-positive (p = 0.035). Median OS was not reached in either arm. As the data are not yet mature, patients continue to be followed for this endpoint.
REFERENCES
- Gomez D et al., Local consolidative therapy (LCT) improves progression-free survival (PFS) in patients with oligometastatic non-small cell lung cancer (NSCLC) who do not progress after front line systemic therapy (FLST): results of a multiinstitutional phase II randomized study. J Clin Oncol 34, 2016 (suppl; abstr 9004)
More posts
PFS improvement due to local therapy in oligometastatic NSCLC
Evidence suggests the existence of a ,limited metastatic’ NSCLC phenotype. However, the type of optimal treatment and the role of aggressive local therapy in these patients remain controversial. Gomez et al. presented the first prospective, randomised trial to address this question. Patients had stage IV disease without RECIST progression and a maximum of three metastases after front-line systemic therapy (FLST).
Locally advanced NSCLC: oral vinorelbine shows better safety profile than etoposide
The randomised, multicentre, open-label, phase II RENO trial was conducted with the objective of establishing a standard chemotherapy regimen in the setting of chemo-radiotherapy of locally advanced NSCLC. A total of 134 patients with inoperable stage III NSCLC received either oral vinorelbine plus cisplatin or etoposide plus cisplatin.
ULTIMATE: chemotherapy plus bevacizumab beyond first line
As chemotherapy in the second-line or third-line settings of NSCLC shows limited efficacy, the phase III, randomised ULTIMATE trial tested the combination of chemotherapy and bevacizumab in patients with advanced NSCLC of non-squamous histology, who had progressed after one or two lines of treatment.
New approaches are raising hope for SCLC patients
Only minor progress has been made over the past 30 to 40 years in the treatment of small-cell lung cancer (SCLC), which accounts for 10 % to 15 % of lung cancer cases. SCLC is radiosensitive, but approximately 70 % of patients present with extended disease that cannot be included within one radiotherapy field. The majority of patients respond to first-line chemotherapy.
Mutational analysis: on the road to refined standards
The Lung Cancer Mutation Consortium (LCMC) is a multi-institutional consortium for the study of driver mutations of lung adenocarcinoma. The cooperating sites enable the identification of relatively large numbers of patients with uncommon and rare alterations, facilitate the analysis of their clinical characteristics, and lay the ground for targeted therapy trials.
“The importance of first-line and second-line targeted agents is obvious”
Which parameters should be taken into consideration regarding the choice of EGFR TKIs in a lung cancer patient with an activating EGFR mutation? When EGFR mutations are diagnosed in the first-line setting, we have the luxury of having three options today. However, it is important to discriminate between the different types.