Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

Kanda, Shintaro; Goto, Kumiko; Shiraishi, Hiroaki; Kubo, Emi; Tanaka, Ayako; Utsumi, Hirofumi; Sunami, Kuniko; Kitazono, Satoru; Mizugaki, Hidenori; Horinouchi, Hidehito; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Hozumi, Hironao; Tamura, Tomohide

doi:10.1093/annonc/mdw416

Cited by 88 publications

(70 citation statements)

References 18 publications

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“…The aim of combination strategies is to mediate antitumor efficacy or reduce side effects. New combinations of PD1/PD‐L1 antibodies with chemotherapy or other immune checkpoint inhibitors have been investigated as first‐line treatments . However, the most efficacious of these therapeutic strategies in lung cancer is not known.…”

Section: Discussionmentioning

confidence: 99%

The efficacy and safety of anti‐PD‐1/PD‐L1 antibodies combined with chemotherapy or CTLA4 antibody as a first‐line treatment for advanced lung cancer

Huang

Zheng

et al. 2018

Intl Journal of Cancer

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Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small-cell lung cancer (NSCLC). This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of NSCLC were 47.0% (95% CI: 34.2%-60.2%) and 80.9% (95% CI: 69.4%-88.7%), respectively. The combined ORR and DCR for CTLA4 antibody combined with chemotherapy for the treatment of small-cell lung cancer (SCLC) were 65.4% (61.1%-69.5%) and 87.6% (84.5%-90.2%), respectively. The combined six-month progression-free survival rates (PFSRs ) for NSCLC and SCLC were 50.2% (95% CI: 21.9%-78.4%) and 30.7% (21.2%-40.3%), respectively, and the OSRs were 56.4% (39.1%-73.7%) and 36.9% (33.3%-40.5%), respectively. In addition, the combined ORR and DCR for the checkpoint inhibitors plus CTLA4 antibody treatment group in NSCLC were 29.6% (95% CI: 11.4%-57.8%) and 48.7% (16.8%-81.7%), respectively. In subgroup analyses, a significant improvement in PFS was observed in NSCLC and SCLC, with a combined hazard ratio and 95% confidence interval of 0.841 (0.737-0.961) and 0.856 (0.756-0.968), respectively. In summary, synergistic activity and an acceptable safety profile were observed with checkpoint inhibitor plus chemotherapy combination treatment in lung cancer.

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Section: Discussionmentioning

confidence: 99%

The efficacy and safety of anti‐PD‐1/PD‐L1 antibodies combined with chemotherapy or CTLA4 antibody as a first‐line treatment for advanced lung cancer

Huang

Zheng

et al. 2018

Intl Journal of Cancer

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“…The case–control study revealed an odds ratio of 0.30 (95% confidence interval 0.18–0.50) for achieving a partial response to salvage chemotherapy . In phase I/II trials, concurrent administration of the PD‐1 inhibitor with first‐line chemotherapy showed a high response rate of > 50% . Chemotherapy has been suggested to synergize with PD‐1 inhibitors in some lung cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

et al. 2017

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Promising outcomes of salvage chemotherapy after nivolumab therapy have been reported; however, little is known about the detailed clinical and immunologic features in lung cancer patients in whom nivolumab is unsuccessful. We report two cases of nivolumab‐refractory lung cancer, in which chemotherapy resulted in rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens showed PD‐ligand 1 (PD‐L1)‐expressing cancer cells, accompanied by tumor‐infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive regulatory T cells and cells positive for TIM‐3 were also observed. Physicians should take caution in treating lung cancer patients after progression on nivolumab. Further studies with a large cohort are warranted to identify the patients that may benefit from salvage chemotherapy.

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“…Although irAEs were greater than those expected with nivolumab monotherapy, most toxicity was manageable [135]. A number of phase I studies are currently underway in NSCLC and other solid tumors including pediatric cancers, aimed at investigating the safety and tolerability of combining ICI with standard chemotherapies [135,136]. …”

Section: Future Directionsmentioning

confidence: 99%

Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies

Park

Cheung

2017

Cancer Treatment Reviews

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Immune checkpoint inhibitors (ICI) have shown great promise in a wide spectrum of adult solid and hematological malignancies, achieving objective tumor responses and prolonging survival. However, there is limited clinical success amongst pediatric patients. In this review, we summarize the current understanding of ICI and present an up-to-date overview of recent and ongoing clinical trials of ICI in pediatric malignancies. In addition, we will discuss immunologic and clinical difficulties in this young population, as well as future prospects for combination of ICI with other immune-based and conventional treatments.

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Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study

Cited by 88 publications

References 18 publications

The efficacy and safety of anti‐PD‐1/PD‐L1 antibodies combined with chemotherapy or CTLA4 antibody as a first‐line treatment for advanced lung cancer

The efficacy and safety of anti‐PD‐1/PD‐L1 antibodies combined with chemotherapy or CTLA4 antibody as a first‐line treatment for advanced lung cancer

Remarkable response of nivolumab‐refractory lung cancer to salvage chemotherapy

Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies

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