LUNAR: Full Moon or Eclipse? An exploration into tumor treating fields in lung cancer

TL;DR

A study on Tumor Treating Fields (TTFs) in lung cancer raises questions about its real-world effectiveness due to flawed trial design and unclear benefits.

Contribution

The paper critically evaluates the LUNAR trial's methodology and questions the validity of TTFs' reported survival benefits in lung cancer.

Findings

The LUNAR trial showed a 3.3-month survival gain with TTFs, but this may be inflated due to trial design flaws.

Unplanned sample size reduction and lack of a sham-control may have biased the results.

Many patients in the trial did not receive standard-of-care treatments like immunotherapy.

Abstract

•Tumor Treating Fields (TTFs) showed a survival gain in metastatic lung cancer.•In the study, patient selection and the control arm did not mirror current practice.•The subgroup who more closely approach the standard-of-care had no benefit.•Unplanned sample size modification raises statistical concerns.•Without a sham-control, TTFs were likely paired with additional supportive care.

Tumor Treating Fields (TTFs) showed a survival gain in metastatic lung cancer.

In the study, patient selection and the control arm did not mirror current practice.

The subgroup who more closely approach the standard-of-care had no benefit.

Unplanned sample size modification raises statistical concerns.

Without a sham-control, TTFs were likely paired with additional supportive care.

The LUNAR trial investigated the addition of Tumor Treating Fields (TTFs) to “standard therapy” in patients with metastatic lung cancer after at least one line of platinum-based chemotherapy. The “standard therapy” was either an anti-PD(L)1 therapy (immunotherapy) or docetaxel. The addition of TTFs provided a 3.3 months median survival gain. We raised concerns about LUNAR results internal and external validity.

First, patient selection and the control arm do not mirror current practice. Two-thirds of patients did not receive prior immunotherapy, which is standard in first-line treatment. Also, the “choice” of the “standard therapy” was restricted by drug availability, resulting in 41 % of patients not receiving immunotherapy during the trial – those allocated to receive docetaxel – had no prior exposure to immunotherapy. Some patients may have harbored actionable mutations, and did not receive targeted therapy.

Second, we raised statistical questions. The sample size was shrunk after an unplanned analysis, with unshared and unclear justifications. The decision may have been influenced by a chance deviation in data favoring the intervention. Also, as significantly more patients were censored after withdrawals in the TTFs group, informative censoring could have amplified the survival gain.

Third and last, without a sham-control design (the equivalent of placebo for devices), it's hard to isolate the impact of TTFs from the extra-attention associated with its administration (continuous 24/7 support, frequent home-based interactions).

Overall, LUNAR do not apply to clinical settings where immunotherapy and molecular testing is offered, and many factors may have artificially boosted the reported survival gain. A sham-controlled trial is needed to answer whether TTFs are beneficial.

The images used in the graphical abstract are both from Tomruen, under CC BY-SA 4.0 :Image, graphical abstract

https://en.wikipedia.org/wiki/Full_moon#/media/File:Supermoon_Nov-14-2016-minneapolis.jpg, no changes were made.

https://en.wikipedia.org/wiki/Lunar_eclipse#/media/File:Lunar_eclipse_oct_8_2014_Minneapolis_4_46am.png, the image was cropped.

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