Rapid Response to the Combination of Lenvatinib and Pembrolizumab in Patients with Advanced Carcinomas (Lung Adenocarcinoma and Malignant Pleural Mesothelioma)

Our plain-English summary of Rapid Response to the Combination of Lenvatinib and Pembrolizumab in Patients with Advanced Carcinomas (Lung Adenocarcinoma and Malignant Pleural Mesothelioma), by W. Shalata, M. Iraqi, B. Bhattacharya, et al (Cancers, 2021).

The study

• Authors: W. Shalata, M. Iraqi, B. Bhattacharya, V. Fuchs, L.C. Roisman, A.Y. Cohen, I. Massalha, A. Yakobson, M. Prasad, M. Elkabets, A. Porgador, N. Peled
• Journal: Cancers
• Published: 2021;13(14)
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The new era of cancer treatments has made immune checkpoint inhibitors (ICIs) and emerging multikinase inhibitors (TKIs) the standards of care, thus drastically improving patient prognoses. Pembrolizumab is an anti-programmed cell death-1 antibody drug, and lenvatinib is a TKI with preferential antiangiogenic activity. We present, to our knowledge, the first reported series of cases consisting of patients with metastatic non-small cell lung cancer and malignant pleural mesothelioma who were treated with several types of chemotherapy combinations and ICIs followed by disease progression. They were subsequently treated with combined immunotherapy and TKI treatment, resulting in a near complete response within a very short time. Clinical responses were supported by in vitro testing of each patient's lymphocytic response to pembrolizumab after pre-exposure of target cancer cells to lenvatinib.

In plain English

This case series from Israel described five patients with advanced cancer: four with lung adenocarcinoma and one woman with malignant epithelioid pleural mesothelioma. The authors stated that all had worsened on standard treatments, though one patient's account described stable disease before the combination began. They received pembrolizumab, an immunotherapy drug, with lenvatinib, a tyrosine kinase inhibitor, off-label. The article did not report whether any patient had been exposed to asbestos. It noted that the mesothelioma patient's father had been diagnosed with mesothelioma. The authors reported a significant response in all five. In the mesothelioma patient, who also received gemcitabine, scans after two months showed a significant decrease in disease; the authors reported nine months' progression-free survival. One lung cancer patient had stable disease for 10 months and then died after a sudden deterioration. Laboratory tests on patients' immune cells and on the mesothelioma patient's tumor tissue gave results the authors saw as supporting the combination. The authors concluded the combination may provide a beneficial option. They noted the small number of patients and that lenvatinib alone was not tested.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case series of five patients, with laboratory (in vitro) tests and tumor tissue grown in mice (patient-derived xenograft) studied outside the body
• Who was studied: Five patients: four with lung adenocarcinoma and one with malignant epithelioid pleural mesothelioma (a 50-year-old woman). The authors stated that all had progressed on standard therapies and were not eligible for clinical trials, although the case account for patient 3 reports stable disease before the combination began. They were treated off-label under approval of the Institutional Review Board of Soroka medical center, Israel. Diagnoses dated from 2016 to 2020; ages were 50 to 68; all had a smoking history.
• Exposure: The article did not report any patient's asbestos exposure history or analyze asbestos exposure. It mentions asbestos only in the introduction, as the background reason mesothelioma is expected to rise. The exposure studied was drug treatment: pembrolizumab (200 mg every 21 days) with daily oral lenvatinib (14 or 20 mg), plus gemcitabine in the mesothelioma patient. The mesothelioma patient's father had been diagnosed with mesothelioma at age 70; no exposure information is given for either of them.
• Main results:
  • The authors reported that all five patients had a significant response to the combination.
  • Mesothelioma patient (patient 4): after two months of pembrolizumab, lenvatinib and gemcitabine, a PET-CT in August 2020 showed a significant decrease in disease. Lenvatinib was stopped in December 2020 after local progression, and the authors gave a progression-free survival of nine months.
  • Lung cancer patient 1: about 40 days after starting the combination, CT showed the left lower lung nodule had completely disappeared. As of June 2021 there was no evidence of disease on scans.
  • Lung cancer patient 3: before the combination, scans after three and after five cycles of earlier treatment showed stable disease. Three weeks after the combination began, PET-CT showed reduced uptake in the right lung, with new uptake in two left ribs (suspected fracture).
  • Lung cancer patient 5: the combination stabilized the disease for 10 months, after which the patient suffered a sudden deterioration leading to death.
  • Adverse events listed for all five patients were diarrhea, fatigue, hypothyroidism, high blood pressure and weight loss. The highest grade shown was 2.
  • Laboratory tests on immune (CD8+ T) cells from patients 1, 2, 4 and 5: cells from patients 4 and 5 released significantly more interferon-gamma with lenvatinib plus pembrolizumab than with pembrolizumab alone (p less than 0.0001). Cells from patients 1 and 2 reached full release with pembrolizumab alone.
  • Tumor tissue from the mesothelioma patient grown in mice and tested outside the body: pre-treatment with lenvatinib followed by T cells and pembrolizumab gave significantly lower tumor-cell proliferation than untreated tissue, and reduced PD-L1 expression.
• The authors' conclusion: The authors concluded that lenvatinib with pembrolizumab may provide a beneficial treatment option for patients with non-small cell lung cancer and malignant pleural mesothelioma, as previously suggested by recent clinical trials.
• Limitations the authors state:
  • The study included a small number of patients.
  • Lenvatinib alone was not tested, so the responses may have come from lenvatinib rather than from the combination.

Topics

Medical terms in this study, explained in our Lexicon: Pembrolizumab (Keytruda), Carcinoma, Lung Adenocarcinoma, Pleural Mesothelioma, checkpoint inhibitors, Non-Small Cell Lung Cancer, Chemotherapy, Disease Progression.

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