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Exceptional pemetrexed sensitivity can predict therapeutic benefit from subsequent chemotherapy in metastatic non-squamous non-small cell lung cancer

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

Based on an exceptionally durable response to pemetrexed observed in some patients with metastatic NSCLC, the predictive value of pemetrexed sensitivity to outcomes of subsequent systemic treatment was investigated.

Methods

We retrospectively reviewed the patients with metastatic non-squamous NSCLC treated with pemetrexed monotherapy as their first- or second-line chemotherapy between November 2006 and February 2015. Good (top 5% longest) and poor responders (bottom 12% shortest) were defined according to the duration of pemetrexed maintenance. The first and second post-pemetrexed (PP) systemic treatments were defined as PP1 and PP2 therapies, respectively, to define their progression-free survivals (PFS) as PFS1 and PFS2.

Results

In a total of 100 patients, 86% of patients received pemetrexed as their second-line chemotherapy, and 34% were classified as good responders. Good and poor responder groups showed 20.5 months and 0.7 months of the median duration of responses, respectively. PP1 and PP2 therapies were done in 74% and 41.9% of patients after failure to pemetrexed. To our surprise, disease control rate (DCR) was significantly higher in the good responder group than poor responder group (69.6% vs 37.3%, p = 0.010) in patients treated with PP1 therapy, and median PFS1 was also significantly longer (5.2 vs 2.2 months, p < 0.01) regardless of the type of subsequent systemic treatment. Meanwhile, pemetrexed sensitivity did not affect DCR or PFS of patients who received PP2 therapies.

Conclusions

Patients who achieved durable response to pemetrexed might obtain greater therapeutic benefits from subsequent systemic treatment in metastatic non-squamous NSCLC without targets, which could potentiate more effective post-pemetrexed treatment strategy.

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Authors and Affiliations

  1. Department of Hemato-Oncology, College of Medicine, Konkuk University Medical Center, University of Konkuk, Seoul, Korea

    Ji Hyun Park

  2. Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea

    Ji Hyun Park, Shinkyo Yoon, Chang-Min Choi & Jae Cheol Lee

  3. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea

    Byoung Soo Kwon, So Jung Park, Wonjun Ji & Chang-Min Choi

  4. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea

    Byoung Soo Kwon

  5. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea

    So Jung Park

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  1. Ji Hyun Park
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Correspondence to Jae Cheol Lee.

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It was conducted in full accordance with the Guidelines for Good Clinical Practice and the 1964 Declaration of Helsinki.

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The study protocol was reviewed and approved by the Institutional Review Board (IRB Approval Number: 2018-0661) of Asan Medical Center, and informed consents were obtained from all individual participants included in the study.

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Park, J.H., Kwon, B.S., Park, S.J. et al. Exceptional pemetrexed sensitivity can predict therapeutic benefit from subsequent chemotherapy in metastatic non-squamous non-small cell lung cancer. J Cancer Res Clin Oncol 145, 1897–1905 (2019). https://doi.org/10.1007/s00432-019-02941-z

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