Efficacy of next treatment received after nivolumab progression in patients with advanced nonsmall cell lung cancer

Abstract

Nivolumab for the treatment of advanced nonsmall cell lung cancer (NSCLC) evaluated in phase III trials showed 50% progression at first evaluation, but better overall survival (OS), suggesting regained efficacy of treatments given thereafter. We aimed to evaluate the efficacy of nivolumab and of next treatment received after nivolumab progression in patients with advanced NSCLC.Our multicentre retrospective study included all patients receiving nivolumab between January and December 2015. The primary end-point was progression-free survival (PFS) of treatment given after nivolumab.The 303 patients had the following characteristics: median age 63 years, 69% males, 92% smokers, 67% performance status 0–1 and 61% adenocarcinoma. Nivolumab was given as second-line treatment in 40% of patients. With 13.7 months of median follow-up, nivolumab PFS and OS were 2.6 and 11.3 months, respectively. At the cut-off analysis 18% were controlled under nivolumab, 14% were deceased and 5% were lost to follow-up under nivolumab. Among the 191 (63%) patients eligible for post-nivolumab (PN) treatment, 115 (38%) received further treatment and were characterised by better performance status (p=0.028) and by receiving more injections of nivolumab (p=0.001). Global PN-OS and PN-PFS were 5.2 and 2.8 months, respectively. Drugs most frequently used after nivolumab were gemcitabine (23%), docetaxel (22%) and erlotinib (16%), with median PFS of 2.8, 2.7 and 2.0 months, respectively.Nivolumab produced similar efficacy as in phase III trials, although patients received nivolumab later and had worse performance status. 38% received treatment after nivolumab progression with efficacy comparable to historical second-line trials.

Management and outcomes of non–small cell lung cancer patients with rapid progression under second‐or‐more‐line immune checkpoint inhibitors: ERORECI study (GFPC 2016‐04)

“…The authors of most studies compared progressor's clinical and biological characteristics to those of responders. Our findings are consistent with those of other studies . Shiroyama et al found ECOG PS and inflammation to be factors associated with RP, whereas, according to Costantini et al's very recent publications, RP was significantly associated with ECOG PS, bone metastases or short duration of pre‐ICI treatment.…”

“…The RP definition varies according to authors. Some base it on the tumor‐doubling time, whereas others rely on death occurring within the 3 months following ICI onset or ≥3 nivolumab infusions . Constantini et al considered patients to have refractory NSCLCs when their disease progressed after one or two nivolumab injections.…”

“…Shiroyama et al retained a threshold of 2 months . Depending on the definition applied, NSCLC RP frequencies ranged from 9% to 20% . The characteristics of those patients also varied but the majority of them had multisite metastatic disease.…”

“…The RP definition of varies according to the authors, but the majority of studies retained 2‐ or 4‐months following ICI onset . Little is known about these patients' characteristics and those of their tumors, therapeutic options post‐ICI and their outcomes …”

Treatment options beyond immunotherapy in patients with wild-type lung adenocarcinoma: a Delphi consensus

“…Several studies have suggested that treatment with immunotherapy does not condition the efficacy of subsequent chemotherapy. On the contrary, these studies seem to suggest an increase in the efficacy of chemotherapy [40][41][42][43][44], particularly when combined with anti-angiogenic agents [45][46][47], when administered after treatment with immunotherapy. Synergistic activity in both preclinical [48,49] and clinical models [21,22,25,26] support a hypothesis of a possible chemosensitization after prior exposure to immunotherapy.…”