Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non

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Phase III Study Comparing Cisplatin Plus
Gemcitabine With Cisplatin Plus Pemetrexed in
Chemotherapy-Naive Patients With Advanced-Stage
NonSmall-Cell Lung Cancer

• AuthorsGiorgio Vittorio Scagliotti, Purvish
  Parikh, Joachim von Pawel, Bonne Biesma, Johan
  Vansteenkiste, Christian Manegold, Piotr
  Serwatowski, Ulrich Gatzemeier, Raghunadharao
  Digumarti, Mauro Zukin, Jin S. Lee, Anders
  Mellemgaard, Keunchil Park, Shehkar Patil, Janusz
  Rolski, Tuncay Goksel, Filippo de Marinis,
  Lorinda Simms, Katherine P. Sugarman, David
  Gandara
• Date posted

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Treatment A Cisplatin 75 mg/m2 Day 1
Gemcitabine 1250 mg/m2 Day 1 8 B12 folic
acid
R
Treatment B Cisplatin 75 mg/m2 Day 1
Pemetrexed 500 mg/m2 Day 1 B12 folic acid
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RESULTS
Cis/Pem Cis/Gem P-value
Response Rate () 31 28 NS
OS (median, mos) 10.3 10.3 NS
OS Adeno (median, mos) 12.6 10.9 .03
OS Squame (median, mos) 9.4 10.8 .05
Toxicity (Grade3/4) Less heme,Feb neutro, alopecia Less nausea/ vomiting
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STUDY COMMENTARY

• This was designed as a non-inferiority trial.
• Have to ask why 1750 patient trial needed to show
  that platinum based doublets are not inferior.
• Significant differential effect based on
  histology seen in second line trials of
  pemetrexed and docetaxel
• Never smokers have significantly better survival
  regardless of treatment. Needs to be considered
  in design of clinical trials.
• Cis/Pem has significantly less hematologic
  toxicity but significantly more emesis.

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• There should be no further trials comparing
  platinum based doublets in unselected populations
  of advanced NSCL cancer patients.
• Here appears to be a real differential treatment
  effect based on histology for some chemotherapy
  agents. This will need to be considered when
  designing the next generation clinical trials.
• Despite the reduced hematological toxicity
  associated with cis/pem and the non-inferiority,
  the significantly higher cost of this regimen
  will likely preclude its routine use as standard
  first line chemotherapy.