Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients with Locally Advanced Pancreatic Cancer Controlled After Four Months of Gemcitabine With or Without Erlotinib

Lauren Lipscomb, Mercer University College of Pharmacy

 

According to the ESMO (European Society for Medical Oncology) Clinical Practice Guidelines, gemcitabine is the standard of care for locally advanced pancreatic cancer and borderline resectable pancreatic cancer. This guideline does not recommend erlotinib for pancreatic cancer treatment. It is thought that chemoradiation serves as a minor role in these patients. These guidelines also mention FOLFIRINOX (folinic acid (leucovorin)/5-FU/irinotecan/ oxaliplatin) as a possible alternative therapy for pancreatic cancer. [1]

A meta-analysis reports that objective response rate and disease control rate with gemcitabine and erlitinib compared to those of just gemcitabine are not significant. It was noted that the adverse event profile of gemcitabine and erlitonib was more severe than that of gemcitabine alone. [2]

Title: Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients with Locally Advanced Pancreatic Cancer Controlled After Four Months of Gemcitabine With or Without Erlotinib [3]
Design International, multicenter, open-label, unblended, phase three randomized trial; N= 442
Objective To assess whether chemoradiotherapy improves overall survival of patients with locally advanced pancreatic cancer controlled after four months of gemcitabine-based induction chemotherapy and to assess the effect of erlotinib on survival
Study Groups First randomization; N= 442: gemcitabine alone (n= 223); gemcitabine plus erlotinib (n= 219)

Second randomization after 4 months; N= 269: chemotherapy (n= 136); chemoradiotherapy (n=133)

Methods Patients with locally advanced pancreatic cancer were randomized in a 1:1 ratio. Randomization consisted of a 2-step randomization process. In the first step, patients were randomized to induction chemotherapy with gemcitabine (1000 mg/m2 delivered as a 30- minute intravenous infusion weekly for three weeks, followed by a one-week rest (one cycle), for four cycles) or gemcitabine plus erlotinib (once- daily orally at a dose of 100 mg) for four cycles. For the second step, patients whose cancer was controlled and who had a World Health Organization (WHO) performance status of two or less after completion of induction chemotherapy were randomized a second time to receive either chemotherapy or chemoradiotherapy for an additional two months. Maintenance therapy with 150 mg erlotinib was given to qualified patients.
Duration February 2008 and February 2013
Primary Outcome Measure The overall survival from the date of the first randomization
Baseline Characteristics Frist randomization; No (%) (N= 442) Second randomization; No (%) (N=269)
Gemcitabine (n=223) Gemcitabine – erlotinib (n= 219) Chemotherapy (n= 136) Chemoradiotherapy (n=133)
Median age; y 64 63 63 62
Male sex 117 (52.5) 111 (50.7) 76 (55.9) 58 (43.6
Grade of pancreatic cancer
Well differentiated 56 (25.1) 51 (23.3) 33 (24.3) 31 (23.3)
Moderately differentiated 37 (16.6) 38 (17.4) 23 (16.9) 22 (16.5)
Poorly differentiated 28 (18.1) 23 (10.5) 10 (7.3) 9 (6.8)
Unknown 112 (50.2) 107 (48.8) 70 (51.5) 71 (53.4)
Results Overall Survival; mo (month range) p-value
First randomization (N= 442)
Gemcitabine (n=223) 13.6 (12.3 – 15.3) 0.9
Gemcitabine – erlotinib (n= 219) 11.9 (10.4 – 13.5)
Second randomization (N= 269)
Chemotherapy (n= 136) 16.5 (14.5 – 18.5) 0.26
Chemoradiotherapy (n=133) 15.2 (13.9 – 17.3)
Adverse Events Common Adverse Events: Gemcitabine plus erlotinib:anemia (6.2%), febrile neutropenia (2.4%), diarrhea (6.6%), acneiform rash (3.3%)
Serious Adverse Events: 0%
Percentage that Discontinued due to Adverse Events: 0%
Study Author Conclusions In patients with locally advanced pancreatic cancer with disease controlled after 4 months of induction chemotherapy, there was no significant difference in overall survival with chemoradiotherapy compared with chemotherapy alone, and there was no significant difference in overall survival with gemcitabine compared with gemcitabine plus erlotinib used as maintenance therapy.

 

According to this study, patients with locally advanced pancreatic cancer who were treated with gemcitabine and erlotinib showed no significant difference in overall survival compared to treatment with gemcitabine alone. There was also no significant overall survival difference between the chemotherapy and chemoradiotherapy groups after adjuvant chemotherapy. This study was not blinded which can cause bias. Another possible study should be considered comparing FOLFIRINOX with gemcitabine in patients with pancreatic cancer that is locally advanced.

 

References

  1. M. Ducreux, A. Sa. Cuhna, C. Caramella, et al. Cancer of the pancreas: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Annals of Oncology 26 (Supplement 5): v56–v68, 2015 doi:10.1093/annonc/mdv295
  2. Yang ZY, Yuan JQ, Di MY, et al. Gemcitabine plus erlotinib for advanced pancreatic cancer: a systematic review with meta-analysis. PLoS ONE. 2013;8(3):e57528.
  3. Hammel P, Huguet F, Van laethem JL, 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(17):1844-53.
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