BACKGROUND: The prognosis of metastatic non-small cell lung cancer (NSCLC) has been improved by the use of immune checkpoint inhibitors (ICI). Unfortunately, in some cases, cancer cells will develop resistance mechanisms. In case of progression in a limited number of lesions (oligoprogression), focal treatment with radiotherapy is proposed while continuing the ICI therapy.
METHODS: A cohort of 37 patients with metastatic NSCLC treated with nivolumab (anti-PD-1) in second or subsequent line and who received focal radiotherapy for oligoprogression with continuation of nivolumab was compared with a control cohort of 87 patients no oligoprogressor treated par immunotherapy.
RESULTS: After a median follow-up of 37 months [18; 62], the median progression free survival (PFS) in the radiotherapy-treated cohort was 15.04 versus 5.04 months in the control cohort, with a statistically significant difference (P=0.048). The median PFS following focal radiotherapy in the oligoprogressor group was 7.5 months. In univariate analysis, the presence of lung metastasis was associated with increased PFS, in contrast to the presence of brain metastases, which were associated with decreased PFS in the radiotherapy group. The median overall survival was not reached in both groups, with no significant difference between the two cohorts.
CONCLUSIONS: The combination of focal radiotherapy in case of oligoprogression and continued treatment with nivolumab in the treatment of metastatic NSCLC in the second or subsequent line of treatment seems to be with an increase in PFS.

FOCUS ON RESISTANCE TO TYROSINE KINASE INHIBITORS IN RENAL CANCER: The last decade has seen significant advances in understanding the biology and genetics of kidney cancer, some of which have radically changed treatment standards, including the emergence of targeted therapies. TKIs have significantly improved outcome in patients with metastatic disease. Nevertheless, a subset of patients (approximately 25 %) does not show any clinical benefit from targeted therapies. In many cases, patients initially respond to therapy but resistance to targeted agents has been shown to develop after a median of 6-12 months of treatment. Two general models of tumor resistance to anti-angiogenic agents targeting the VEGF pathway have been proposed: an adaptive (evasive) resistance, which occurs after a prolonged application of a drug (providing a period of tumor control), or intrinsic one (preexisting) non-responsiveness despite the presence of an active agent, showing no therapeutic benefit. Intrinsic resistance is related to tumor redundancy of pro-angiogenic pathways. Acquired resistance is associated with activation of alternative pathways either by upregulation of the VEGF pathway or by recruitment of alternative angiogenic factors responsible for tumor revascularization. Because different combinations and sequences of TKI are tested in clinical trials and immunotherapy (alone or in combination) radically alters patient management in its metastatic disease, the current effort aims at identifying resistance processes, evaluating their importance and proposing rational therapeutic approaches in order to obtain an additional clinical benefit. Our article summarizes the different mechanisms of resistance described in the literature.