Chemoradiation Fails To Boost Pancreatic Cancer OS After Induction Response

Switching to chemoradiotherapy after induction chemotherapy does not improve overall survival in locally advanced pancreatic cancer

medwireNews: Radiotherapy plus capecitabine does not extend the overall survival (OS) of patients with locally advanced pancreatic cancer who have already achieved disease control for 4 months with induction gemcitabine alone or alongside erlotinib , suggests research published in JAMA.

“The results of the LAP07 trial are persuasive that contemporary chemoradiation does not add a survival advantage to chemotherapy alone”, writes Deborah Schrag, from the Dana Farber Cancer Institute in Boston, Massachusetts, USA, in a comment accompanying the research.

While acknowledging that the trial “contributes important new information to help guide treatment decisions for patients with locally advanced pancreas cancer”, she emphasizes the need for molecular markers to predict response to treatment and allow focused approaches.

“In the meantime, chemoradiation need not constitute an essential component of the therapeutic backbone”, Deborah Schrag concludes.

The phase III, open-label LAP07 trial included 223 patients who were initially randomly assigned to receive gemcitabine 1000 mg/m2 per week and 219 patients given gemcitabine plus erlotinib 100 mg/day.

Patients who achieved stable disease or an objective response after 4 months were then re-randomised, with 136 given 2 months of the same gemcitabine regimen (alone or with a higher maintenance dose of erlotinib) and 133 receiving 54 Gy of radiation plus capecitabine.

Interim analysis, after a median of 36.7 months, did not show a significant difference in median OS from date of first randomisation between the patients given chemotherapy at second randomisation and those assigned to receive chemoradiation, at 16.5 versus 15.2 months.

Nor was there any significant difference in median OS from first randomisation between patients given gemcitabine only and those also given erlotinib, at 13.6 versus 11.9 months.

Pascal Hammel, from Hôpital Beaujon in Clichy, France, and co-authors note, however, that continuing with gemcitabine was associated with a higher rate of locoregional progression than the chemoradiotherapy regimen (46 vs 32%) but a lower rate of metastatic progression (44 vs 60%).

Patients assigned to receive erlotinib in the first randomisation had a higher rate of grade 3 or 4 anaemia, febrile neutropenia, diarrhoea and acneiform rash than those given gemcitabine alone.

The two treatment groups after the second randomisation had comparable toxicity except a higher rate of grade 3 or 4 nausea with chemoradiotherapy than gemcitabine.

“Although LAP07 confirmed the safety of radiation therapy with concurrent capecitabine, a further intensification of the chemoradiotherapy regimen seems to be needed”, write the investigators, adding that intensity-modulated radiation therapy or stereotactic treatment may allow a tissue-sparing approach.

References

Hammel P, Huguet F, van Laethem J-L, et al. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib. The LAP07 randomized clinical trial. JAMA 2016; 315: 1844–1853. doi:10.1001/jama.2016.4324

Schrag D. Optimizing treatment for locally advanced pancreas cancer. Progress but no precision. JAMA 2016; 315: 1837–1838. doi:10.1001/jama.2016.4284 .

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