Improved outcomes with pembrolizumab treatment in two cases of double cancer including non-small-cell lung cancer

Hida, Norihito; Satoh, Hiroaki; Yamagishi, Toshio; Hiroshima, Yoshinori; Yoshii, Shinichi; Saito, Takefumi; Hizawa, Nobuyuki

doi:10.1097/cad.0000000000000677

Cited by 6 publications

(11 citation statements)

References 15 publications

(13 reference statements)

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“…This treatment resulted in lung cancer shrinkage, and allowed colon cancer excision, confirming histological effects (16). Immune checkpoint therapy in two other patients has been reported by Yamada et al (17). According to this report, these patients had double primary cancers, which were treated with pembrolizumab.…”

Section: Discussionsupporting

confidence: 65%

“…In one of these patients, shrinkage of lung cancer was obtained, but no therapeutic effect was observed in comorbid bladder cancer. In the other case, no reduction in lung cancer was obtained, but a treatment effect on gastric cancer was achieved (17). For synchronous locally advanced or metastatic cancers of lung and nasopharynx, however, there is no established standard therapy.…”

Section: Discussionmentioning

confidence: 96%

“…There have only been few reports on immune checkpoint inhibitors being administered to double primary cancers including lung cancer (16,17). One patient had synchronous in vivo 34: 389-392 (2020) 390 squamous cell lung cancer and colon cancer, which were treated with pembrolizumab (16).…”

Section: Discussionmentioning

confidence: 99%

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Combined Atezolizumab and Chemotherapy for a Patient With Double Primary Cancers

Okauchi

Sasatani

Ohara

et al. 2019

In Vivo

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Background: Immune checkpoint inhibitors are indicated for non-small cell lung cancer (NSCLC) and head and neck cancer, and combined treatment of immune checkpoint inhibitor and chemotherapy has recently been carried out in patients with NSCLC. However, there is no established standard therapy for synchronous locally advanced or metastatic cancers of lung and nasopharynx. Case Report: We report a case of a metastatic lung adenocarcinoma and locally advanced epipharyngeal carcinoma successfully treated with chemotherapy and immune checkpoint inhibitor, paclitaxel, carboplatin, bevacizumab and atezolizumab. The tumor proportion score of programmed death ligand 1 was 5-10% and 70-80% for metastatic lung adenocarcinoma and locally advanced epipharyngeal carcinoma, respectively. Shrinkage of both carcinomas was confirmed, and the treatment effect was judged to be a partial response. Conclusion: This was the first patient who was treated with this combination treatment. Our clinical experience suggests that this treatment could be one of the options for patients with these advanced cancers and an overall good clinical condition.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 96%

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Combined Atezolizumab and Chemotherapy for a Patient With Double Primary Cancers

Okauchi

Sasatani

Ohara

et al. 2019

In Vivo

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“…B16-F10 tumors mice were administrated by oral gavage with PCC0208025 at 30 mg/kg or 60 mg/kg, twice daily. On days 7,9,11,14,16,18 and 20, tumor volumes were detemined. (DOCX) S5 Table. Effects of PCC0208025 on tumor weight in B16-F10 tumor isograft model.…”

Section: S3 Table the Statitic Results And P Values For Effects Of Pmentioning

confidence: 99%

“…In the tumor microenvironment, the activated PD-1/B7-H1 (programmed cell death 1/ PD-L1) signaling pathway makes T lymphocytes functionally inactivated [2,5], which decreases the anti-tumor activity of T cells. So far, the PD-1 antibodies (pembrolizumab and PLOS ONE PLOS ONE | https://doi.org/10.1371/journal.pone.0228339 March 26, 2020 1 / 15 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 nivolumab), have been approved for the treatment of the advanced melanoma [2,6,7]. In addition, the PD-1 receptor ligand (PD-L1) antibodies (BMS-936559 and atezolizumab) have been studied for treating melanoma in preclinical mouse models and clinical trials [2,8].…”

Section: Introductionmentioning

confidence: 99%

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice

et al. 2020

PLoS ONE

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The increased PD-L1 expression induces poorer prognosis in melanoma. The small molecule inhibitors of PD-1/PD-L1 pathways have been an encouraging drug development strategy because of good affinity and oral bioavailability without immunogenicity and immunotoxicities of PD-1/PD-L1 antibodies. In this study, we studied the effects of PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, on PD-1/PD-L1 binding and the cytokines secretion in human CD3 + cells in vitro. We also investigated the antitumor and immunomodulatory activity of PCC0208025 and the pharmacokinetics properties in B16-F10 melanoma-bearing mice. The results showed that PCC0208025 inhibited the PD-1/PD-L1 proteins binding, and rescued PD-L1-mediated inhibition of IFN-γ production in human CD3 + T cells in vitro. Furthermore, in B16-F10 melanoma-bearing mice, PCC0208025 presented the antitumor effects, enhanced IFN-γ levels in plasma, increased the frequency of CD3 + CD8 + T and CD8 + IFN-γ + T and the ratios of CD8 + /Treg, and deceased the CD4 + CD25 + CD127 low/− (Treg) number in tumor. Pharmacokinetics study found that PCC0208025 was absorbed and distributed into the tumors with much higher concentrations than those of the blockade against PD-1/PD-L1 binding. Our work suggests that PCC0208025 exhibited anti-tumor effects through inhibiting Treg expansion and increasing cytotoxic activity of tumor-infiltrating CD8 + T cells by the blockade of PD-1/PD-L1 binding, which may provide the pharmacological basis to develop small molecule inhibitors of PD-1/PD-L1 binding for PCC0208025 as a lead compound.

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Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer

Hao,

Zhang,

Cui

et al. 2024

Cancer Medicine

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BackgroundAlthough the incidence of double primary cancers (DPCs) involving lung cancer is rising, they have not been studied sufficiently. This study retrospectively analyzed the clinicopathological and prognostic characteristics of DPC patients with lung cancer and developed a survival nomogram to predict the individual OS rates.MethodsWe included 103 DPC patients with lung cancer from Shengjing Hospital between 2016 and 2021. Based on the 6‐month cancer occurrence interval, the cases were categorized as synchronous DPCs (sDPCs) or metachronous DPCs (mDPCs). Furthermore, the mDPCs were subdivided based on whether the lung cancer occurred first (LCF cohort) or the other cancer occurred first (OCF cohort).ResultsAmong the patients, 35 (33.98%) and 68 (66.02%) had sDPCs and mDPCs, respectively. In the mDPCs cohort, 18 (26.47%) belonged to the LCF cohort and 50 (73.53%) to the OCF cohort. The most frequent primary cancer sites were the breast (27.18%), colorectum (22.33%), and urinary system (18.45%). Independent risk factors for progression‐free survival were Stage IV lung cancer (p = 0.008) and failure to undergo radical lung cancer surgery (p = 0.028). The risk factors for OS included squamous carcinoma (p = 0.048), Stage IV lung cancer (p = 0.001), single cancer resection plus drug therapy (p < 0.001), drug therapy alone (p = 0.002), failure to undergo radical lung cancer surgery (p = 0.014), and chemotherapy (p = 0.042). The median OS was 37 months, with 3‐ and 5‐year rates of 50.9% and 35.9%, respectively.ConclusionDPCs involving lung cancer account for 1.11% of cases. The breast, colorectum, and urinary system were the most common extra‐pulmonary sites, and mDPCs were more frequent than sDPCs. Radical lung cancer surgery significantly affects prognosis, and drug therapy alone may be preferable when only one tumor is operable. The developed nomogram can accurately predict individual 3‐year and 5‐year OS rates.

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Improved outcomes with pembrolizumab treatment in two cases of double cancer including non-small-cell lung cancer

Cited by 6 publications

References 15 publications

Combined Atezolizumab and Chemotherapy for a Patient With Double Primary Cancers

Combined Atezolizumab and Chemotherapy for a Patient With Double Primary Cancers

PCC0208025 (BMS202), a small molecule inhibitor of PD-L1, produces an antitumor effect in B16-F10 melanoma-bearing mice

Clinicopathological features, prognostic factor analysis, and survival nomogram of patients with double primary cancers involving lung cancer

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