Article and Video CATEGORIES

Cancer Journey

Search By

Dr. Jack West is a medical oncologist and thoracic oncology specialist who is the Founder and previously served as President & CEO, currently a member of the Board of Directors of the Global Resource for Advancing Cancer Education (GRACE)

 

PF299804 vs. Tarceva: Added Benefit Over a Current Standard?

Please Note: New Treatments Have Emerged Since this Original Post
Author
Howard (Jack) West, MD

In my last post, I described the novel oral agent PF299804 (PF299), an irreversible "pan-HER" inhibitor not only of the epidermal growth factor receptor but of other members of the human epithelial growth factor receptor (HER) family. We covered some small studies in patients previously treated with chemotherapy and an EGFR inhibitor, with these studies demonstrating that this new agent clearly has activity, shrinking a minority of tumors, with many other patients demonstrating prolonged stable disease even after several lines of prior therapy. This suggests that this agent can provide some additional benefit beyond that conferred by a reversible EGFR inhibitor that we already have available, namely Tarceva (erlotinib) or Iressa (gefitinib). But another way to ask about how much PF299 offers over a currently available standard oral EGFR inhibitor is to compare them directly in patients who have never received prior therapy against EGFR. That study has been done and was presented at ASCO 2010.

Michael Boyer, out of Sydney, Australia led a randomized phase II trial that was conducted at a handful of centers around the world. The study enrolled 188 patients with advanced NSCLC and tissue available for molecular marker studies, who had previously received one or two prior lines of chemotherapy but hadn't received EGFR inhibitor therapy. Patients were randomized to receive either daily Tarceva at the standard 150 mg daily dose, or PF299 at 45 mg by mouth daily. The primary endpoint was progression-free survival (PFS), and the investigators also looked at tumor response rate, side effects, and several other measures. They planned subset analyses of PFS results based on clinical and molecular variables as well. It's worth noting that while the two arms were well balanced for many variables, it just happened to work out that the PF299 arm had a higher proportion of patients with an EGFR mutation (20% vs. 12%). On the other hand, more patients on the PF299 arm had a marginal performance status of 2 (19% vs. 3%), which would be expected to disfavor the PF299 arm. The trial demonstrated a significantly higher response rate with PF299 vs. Tarceva (17% vs. 4%, p = 0.009) as well as a significantly improved PFS in recipients of PF299 in the overall trial population (p - 0.019). pfs-pf299-vs-erlotinib-entire-population (click on image to enlarge) What was especially interesting was that there didn't seem to be any isolated subgroup that received a much greater benefit with PF299 vs. Tarceva, or vice versa. Instead, just about all subgroups had similar degree of modestly superior PFS in the recipients of PF299. In the figure below, the blue boxes situated to the left of the vertical line on the right side represent improvement with PF299 over erlotinib (and the more to the left, the stronger the benefit). There are no blue boxes that fall to the right of the bar to signify better results with Tarceva. pfs-pf299-vs-erlotinib-forest-plot-subgroups In these plots, the width of the various boxes is proportional to the size of the group, and the horizontal lines extending from it represent the degree of variability in the results. So we see that whether patients have an EGFR mutation or wild type, KRAS mutation or wild type, adenocarcinoma or non-adenocarcinoma, men or women, never-smoker or ever-smoker, and Asian or another race, the trend favored PF299 to a similar degree of about 30-40%. The only subset that didn't show that trend was comprised of patients 65 or older, which was a small group, and in whom the results were remarkably similar between PF299 and Tarceva. This study also provided an opportunity to directly compare PF299 in terms of side effects to an agent we've become very familiar with. These results showed that side effects may well be a concern and potential limitation for PF299, at least at the dose studied. "Dermatitis acneiform", as opposed to "rash", was more common with PF299 (though I think it may be splitting hairs to try to understand how they categorized dermatitis acneiform compared to rash). Also, nailbed infections, mouth sores, and diarrhea were all more common and tended to be more severe with PF299 vs. Tarceva. Since there are certainly patients for whom side effects of Tarceva can be a real challenge, it sounds to me like PF299 may be more difficult for many patients to navigate, even if side effects were most often in the mild to moderate range. The authors concluded that this work is promising enough to warrant a larger, randomized phase III trial with the same design, and I certainly agree. Other studies with PF299, both in EGFR inhibitor-treated and naive patients are likely to be pursued in the next few years, and I certainly would be eager to have my patients participate. It may well prove to be an agent that not only can provide additional benefit to the minority of patients who have an initial response to an EGFR inhibitor and then become resistant, but also appears likely to provide a meaningfully greater efficacy than Tarceva in a much broader population of patients, in various clinically and molecularly defined subgroups. It will be important for future trials and overall clinical experience to better define that advantage and explore the potentially increased toxicity challenges that may be a real limitation for some patients.

Next Previous link

Previous PostNext Post

Related Content

Image
Bladder Cancer Video Library 2024
Video
Dr. Petros Grivas discusses intravesical treatment for patients with nonmuscle invasive, or early-stage, bladder cancer, the importance of participating in clinical trials for bladder cancer, combination therapy options for patients with metastatic or incurable bladder cancer, and the importance of family history of cancer and discussing that history with your doctor.
Image
Case Based Panel
Video
The panel discusses treatment options for a patient diagnosed with EGFR Exon 19 Deletion NSCLC and examines data from the Laura Trial, a patient with a smoking history and diagnosis of small cell lung cancer, and how the Adriatic Study factors into decisions, and a patient with NSCLC adenocarcinoma, and a EGFR Exon 21 L858R Alteration, and how data from the Flaura 2 Trial can impact treatment decisions.
Image
Terapias Dirigidas de Cancer de Pulmón 2024
Video
La Dra. Estelamari Rodríguez presenta información básica sobre el NSCLC EGFR+ y analiza la importancia de las pruebas de biomarcadores en el cáncer de pulmón y ofrece una descripción general de las opciones de tratamiento para la enfermedad EGFR+.  Para ver la playlist completa, de click aquí.        

Forum Discussions

Hello Linda, my name is Alexandra Beneke, I'm the Outreach Manager for GRACE. Your willingness to share your experiences and knowledge with the cancer community is truly inspiring. Your dedication to...

Hi Bluebird,  Welcome to GRACE.  I'm sorry you're going through this scare and hope it's just inflammation or from an infection you didn't know you had. 

 

A CT would be...

Radiation + Brain Operation has just been discarded due to high risk. They will double Tagrisso dosis and then wait to see if it works, then try traditional Chemo. I would...

Hi and welcome to GRACE.  I'm sorry to know you are entering a new stage.  I'm not about to comment just now but wanted to let you know I see your...

Edit to say, we can't give advice but we can comment with views and facts.  :)

 

My first thought is to ask if she has been seen at a large...

Hi Barbro, Welcome to GRACE. I'm sorry you're worrying about this. We aren't able to give feedback on scan reports. Interpreting scan reports in this setting is not only unethical but...

Recent Comments

JOIN THE CONVERSATION
Tagrix FDA Approval
By mariachristian on
Hi Judy! It is so good to…
By JanineT GRACE … on
Tagrix vs Tagrisso
By Dipakchavan on
Hello Linda, my name is…
By AlexandraGBeneke on