No NSCLC Survival Benefit for High-Dose Radiation, Cetuximab

Increasing the radiation dose or adding cetuximab therapy fails to improve non-small-cell lung cancer patient overall survival after chemoradiotherapy

medwireNews: For patients with inoperable stage IIIA or IIIB non-small-cell lung cancer, 60 Gy radiotherapy in 2 Gy fractions with concurrent carboplatin and paclitaxel remains the best strategy, phase III trial results show.

The RTOG 0617 open-label study failed to show an overall benefit for increasing radiation dose to 74 Gy or for the addition of the Epidermal growth factor receptor (EGFR) inhibitor cetuximab, the authors report in The Lancet Oncology.

However, Jeffrey Bradley, from Washington University in St Louis, Missouri, USA, and team say that the median overall survival (OS) of 28.7 months for 217 patients given a 60 Gy dose, with 58% alive at 2 years, is “better than anticipated” and sets a “new benchmark” for this patient population.

This compares with significantly poorer OS of 20.3 months and 45% alive at 2 years for the 207 patients given 74 Gy, suggesting that high-dose treatment “might be potentially harmful”, they report.

With computed tomography or PET scans assessed for most patients, the researchers add: “Notably, this is the first RTOG phase 3 trial that incorporated diagnostic PET [positron emission tomography] for disease staging.“ Thus, stage migration might contribute to the reason the 60 Gy group did better than anticipated”, they hypothesise.

Median OS did not significantly differ for the 237 patients who were randomly assigned to receive cetuximab throughout consolidation therapy and the 228 who did not receive the EGFR inhibitor, at a median 25.0 and 24.0 months, respectively.

But immunohistochemical staining results available for half the population indicated that median OS was 42.0 months among patients with EGFR overexpression who received cetuximab versus 21.2 months if they did not, suggesting that it might benefit this subpopulation.

By contrast, median OS among patients with low EGFR expression was significantly poorer among cetuximab-treated patients than controls, at 19.5 versus 29.6 months, indicating cetuximab may be “detrimental” in this subgroup.

“These data should not change practice, but they are worthy of further exploration in subsequent trials”, say Jeffrey Bradley and team.

Writing in an accompanying comment, Corinne Faivre-Finn, from the University of Manchester in the UK, notes that treatment-related deaths are likely to be a “major” factor for the reduced survival in the high-dose group.

Thus, future studies should “enforce stricter heart and lung constraints and encourage the use of intensity-modulated radiotherapy for the treatment of large and complex volumes”, she says.

Alternative means of treatment intensification to improve local control and survival in NSCLC patients include “dose escalation with altered fractionation, individualised radiation dose escalation based on normal tissue dose constraints or functional imaging, stereotactic ablative radiotherapy boost, and the addition of targeted agents and immunotherapy to radiation”, she adds.

References

Bradley JD, Paulus R, Komaki R, et al. Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 2015; Online First 15 January. DOI: dx.doi.org/10.1016/S1470-2045(14)71207-0

Faivre-Finn C. Dose escalation in lung cancer: have we gone full circle? Lancet Oncol 2015; Online First 15 January. DOI: dx.doi.org/10.1016/S1470-2045(15)70001-X

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