Clinical activity, safety and predictive biomarkers results from a phase Ia atezolizumab (atezo) trial in extensive-stage small cell lung cancer (ES-SCLC)

Sequist, Lecia V.; Chiang, AK; Gilbert, Jennifer L.; Gordon, M.; Conkling, Paul; Thompson, Dola S.; Marcoux, Judith; Antonia, S.; Liu, B.; Shames, David S.; López-Chávez, Ariel; O’Hear, Carol; Fassò, Marcella; Gettinger, Scott

doi:10.1093/annonc/mdw389.03

Cited by 34 publications

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“…Recently, checkpoint blockade immunotherapy received promising attention in the treatment for ED-SCLC. Although phase II [32] and III [33] trial showed no significant differences between the control and ipilimumab (anti-CTLA4) groups, PD-L1 antibody (nivolumab, pembrolizumab, atezolizumab) showed its safety and clinical efficacy [34][35][36][37]. Furthermore, recent clinical studies demonstrated that combined treatment with pembrolizumab and chemotherapy showed significantly benefit in advanced NSCLC [38,39], advanced or metastatic platinumrefractory urothelial cancer [40], and advanced gastric or gastroesophageal junction adenocarcinoma [41].…”

Section: Discussionmentioning

confidence: 99%

A randomized phase 2 trial of apatinib vs observation as maintenance treatment following firstline induction chemotherapy in extensive stage small cell lung cancer

et al. 2019

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Background The 5-year survival rate for extensive-disease small-cell lung carcinoma (ED-SCLC) is only 1%. Recently, apatinib exerted promising effects on cancer patients after failure of first-line chemotherapy. Methods This study enrolled 24 ED-SCLC patients to study the efficacy and toxicity of apatinib in combination with chemotherapy and maintenance therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib was given 250 mg/day during the chemotherapy interval, and as maintenance therapy after 4-6 cycles until the patient progressed, died, or was intolerant to drug toxicity. The study further evaluated the cytotoxicity, cell-cycle arrest and apoptotic induction of apatinib in A549 and H446 cells. Results There was no difference in short-term efficacy between combined and chemotherapy groups. Long-term efficacy showed that the median PFS was 7.8 months and 4.9 months in combination and chemotherapy groups, respectively [p = 0.002, HR(95%CI): 0.18(0.06-0.60)]. The median OS was 12.1 months and 8.2 months in combination and chemotherapy groups, respectively [p = 0.023, HR(95%CI): 0.38 (0.16-0.90)]. Multivariate Cox regression analysis showed that apatinib combined with chemotherapy was an independent prognostic factor for OS and PFS. The ECOG score was an independent prognostic factor affecting OS. In vitro analysis showed that apatinib inhibited cell proliferation and caused cell-cycle arrest and apoptosis. Conclusion Apatinib combination/maintenance therapy showed promising efficacy and safety to extend OS/PFS in ED-SCLC and will be a potent therapeutic option in future practice. Although the scale of this study is small, further research on large sample sizes is needed.

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Section: Discussionmentioning

confidence: 99%

A randomized phase 2 trial of apatinib vs observation as maintenance treatment following firstline induction chemotherapy in extensive stage small cell lung cancer

et al. 2019

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“…Patients with SCC and NSCLC showed similar survival benefits. The PCD4989g study 54 was a Phase I study that investigated atezolizumab treatment for diverse solid tumors containing SCLC. This study included 17 SCLC patients with brain metastasis, 65% of whom had received third-line or above treatment.…”

Section: Sclcmentioning

confidence: 99%

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Wang

Xie

et al. 2020

OTT

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The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes in the blood-brain barrier in the tumor microenvironment suggests that immunocytes are fully capable of entering and exiting the CNS. Emerging clinical data suggest that inhibitors of programmed death receptor-1/programmed death ligand 1 (PD-1/PD-L1) can stimulate surrounding T cells and thus have antitumor effects in the CNS. For example, PD-1 antibody (pembrolizumab) monotherapy has displayed a 20-30% encephalic response rate in patients with brain metastases from malignant melanoma or non-small cell lung cancer. Combined application of nivolumab and ipilimumab anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 showed an encephalic response rate of 55% in patients with brain metastases of melanoma. Further evidence is required to verify these response rates and identify the mechanisms of curative effects and drug tolerance. While regional treatments such as whole-brain radiosurgery, stereotactic radiosurgery, and brain surgery remain the mainstream, PD-1/PD-L1 inhibitors display potential decreased neurotoxic effects. To date, five drugs have been approved for use in patients with encephalic metastases of lung carcinoma: the anti-PD-1 drugs, pembrolizumab and nivolumab, and the anti-PD-L1 agents, atezolizumab, durvalumab, and avelumab. In recent years, clinical trials of inhibitors in combination with other drugs to treat brain metastasis have also emerged. This review summarizes the biological principles of PD-1/PD-L1 immunotherapy for brain metastasis of lung cancer, as well as ongoing clinical trials to explore unmet needs.

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“…The notion that paraneoplastic syndromes are often accompanied by T-cell mediated antitumor immunity 3, together with the recent evidence that SCLC has one of the highest rate of mutation burden (4), have further enhanced the hope for an efficacious application of checkpoint inhibitors in SCLC treatment. Both PD-1 inhibitors nivolumab (5,6) and pembrolizumab (7) as well as the anti-PD-L1 atezolizumab (8) control. Similarly the CheckMate 451 study did not show any survival benefit with nivolumab plus ipilimumab versus placebo as maintenance therapy in patients with extensive-stage SCLC who completed first-line platinumchemotherapy.…”

Section: 3 Months;mentioning

confidence: 99%

“…The predictive role of tumor PD-L1 expression has not been evaluated in the IMPower133 trial, since data emerging from phase I studies (5,7) clearly demonstrated that PD-L1 has generally low expression on tumor cells and did not correlate to immunotherapy efficacy. Conversely, the expression of PD-L1 in the stroma seems to be higher and significantly associated with survival outcomes of pre-treated patients included in the KEYNOTE-028 and 158 trials (7,8), and its predictive value is currently investigated in the first-line KEYNOTE-604 study comparing Pembrolizumab plus platinum-chemotherapy vs. chemotherapy alone in extensive-stage, naive SCLC patients. Even if crucial, the biomarker-driven treatment strategy will inevitably meet several criticisms, considering the limited, low quality, and often cytological samples that are almost always used to obtain SCLC diagnosis, likely imposing a radical change of tissue collection practice.…”

Section: 3 Months;mentioning

confidence: 99%

Immunotherapy in first line for extensive-stage small-cell lung cancer: another piece is going to fill the puzzle?

Passiglia

Novello

2018

Ann. Transl. Med

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Clinical activity, safety and predictive biomarkers results from a phase Ia atezolizumab (atezo) trial in extensive-stage small cell lung cancer (ES-SCLC)

Cited by 34 publications

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A randomized phase 2 trial of apatinib vs observation as maintenance treatment following firstline induction chemotherapy in extensive stage small cell lung cancer

A randomized phase 2 trial of apatinib vs observation as maintenance treatment following firstline induction chemotherapy in extensive stage small cell lung cancer

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Immunotherapy in first line for extensive-stage small-cell lung cancer: another piece is going to fill the puzzle?

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Clinical activity, safety and predictive biomarkers results from a phase Ia atezolizumab (atezo) trial in extensive-stage small cell lung cancer (ES-SCLC)

Cited by 34 publications

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A randomized phase 2 trial of apatinib vs observation as maintenance treatment following first­line induction chemotherapy in extensive­ stage small cell lung cancer

A randomized phase 2 trial of apatinib vs observation as maintenance treatment following first­line induction chemotherapy in extensive­ stage small cell lung cancer

<p>Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer</p>

Immunotherapy in first line for extensive-stage small-cell lung cancer: another piece is going to fill the puzzle?

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A randomized phase 2 trial of apatinib vs observation as maintenance treatment following firstline induction chemotherapy in extensive stage small cell lung cancer

A randomized phase 2 trial of apatinib vs observation as maintenance treatment following firstline induction chemotherapy in extensive stage small cell lung cancer