Catherine Ménard

Development of a compound in the oncology therapeutic area is constantly evolving, and costs are rising dramatically, making every step count. Three essential assets should be acquired before an oncology trial is launched.

 A potent compound originates from rigorous pre-clinical models, so these models should take several factors into account, including the selection of the patient populations, the mode of administration of the drug as well as the formulation. The use of pharmacodynamic markers (PD markers), which may lead to the development of a companion diagnostic tool, are also developed during this important first step.

 The validation of the appropriate pre-clinical models is the first prerequisite in the development process. Those models will provide some efficacy and safety data and will generate interest in the new compound. This is followed by a series of toxicological studies as defined by ICH guidelines for pre-clinical studies that will define the toxicological profile of the drug to establish the initial dosage in humans. Having a strong model at the beginning of the process will lead to more successful translational studies, meaning more relevant and robust pre-clinical data, which has a direct impact on the potential commercialization of that compound.

 Academic/biotech researchers are creative minds that must fit within stringent regulatory and commercial boundaries. This can sometimes be a challenge when faced with the competitive realities of compound development, where profit potential and opportunities for licensing deals may trump scientific interest. For small drug companies especially, the early stages of development are the most challenging from a financial standpoint as well as in terms of innovation. To avoid costly missteps along the way, it can be prudent to rely on the guidance of those who have been through the process before.

 A robust scientific  model alone will not guarantee success. The science  behind the product must show more than a  strong hypothesis in addition to reliable results. It  also needs to be innovative and, more importantly,  resistant over time.

Developers will see a much greater return if  they invest time and money in adapting their technology  to fit a long-term development plan. Scientists  must see beyond the limits of good fundamental  science and open themselves up to  the clinical necessities and daily realities of both  medical oncologists and their patients for a longterm,visionary drug development plan.

In the short run, a development plan should include  the feasibility throughout all phases of clinicaltrials (from Phase I through III). Long-term development plans present the biggest challenge for developersbecause they not only need to define the product placementin today’s market but for as long as 10 years down the road.

This involves not just the product, but also the standard ofcare and comparator compounds to be used throughout theclinical development process to accurately assess the drug’sefficacy. Developers are increasingly likely to invest in comparativestudies to ensure they are launching accurate, state-of-the-art products. This will require help from marketing toforesee what the comparator drugs are likely to be over thenext 5-to-10 years. This long-term projection is also applicableto patent life, which also presents competition from genericequivalents that are impossible to avoid.

The National Cancer Institute is currently conducting multicenter  trials to test a new method of monitoring patient adverse  events through the Patient-Reported Outcomes version of the  Common Terminology Criteria for Adverse Event (PRO-CTCAE).  The PRO-CTCAE provides a web-based platform to collect patient  reports of symptoms they are experiencing while undergoingtreatment, for the purpose of enhancing adverse event reporting.

 PRO-CTCAE is based on findings that suggest the reporting  of adverse events directly from the patients is significantly correlated  with measures of functional performance and health  status, as opposed to adverse events reported by clinical staff.

  This secure, web-based platform for patients, investigators, and  clinicians is also thought to be more accurate and reliable than  patient self-report questionnaires and allows adverse events to  be directly reported by cancer patients taking part in clinical trials,  instead of having them interpreted and modified by clinical  staff to fit the CTCAE.

  A visionary development plan that is open to more sophisticated  patient-tailored tools and that shares long-term clinical  goals with every stakeholder touched by the disease, i.e. developers,  investors, medical and para-medical teams, patients  and their relatives, will contribute greatly to the optimization of  treatments against cancer.

 Bringing together a strong  leadership team that can pull in complementary experts and  strategic partners to help get it all done on time and within budget  is recommended.

   These partnerships will bring different expertise to the multifaceted   challenges faced during the drug development process.   These can include, among other things: refining the technology;   overseeing the regulatory requirements and ensuring   quality assurance; managing pharmacovigilance; facilitating   operations during clinical trials and accelerating the overall   trial process; developing or advising on software; elaborating   and launching the business and commercialization process;   developing patents and providing legal advice; and promoting   collaboration with Key Opinion Leaders in the industry.

   The medical oncology community is key to helping drug   developers uncover real-world needs of patients and are,   therefore, essential throughout the drug development   process. But, strong and trustworthy alliances with medical   oncologists is not always a given for biotechnology   companies. However, a CRO that specializes in oncology   may deliver an added advantage as it already maintains   strong relationships with oncologists, which will facilitate   the collaboration between sponsors and potential investigators   or other clinical oncology experts. CROs may   also offer specific services in various activities from early   to late stage product development. The expertise of both   the medical oncologist and the CRO will combine to help   transpose preclinical models into the reality of the clinical   world and in doing so will optimize translational studies.

   A CRO may also work closely with the developer’s scientific   team in early stage phases to reevaluate the objectives of   the trial and the protocol design according to the industry’s   requirement, and taking into account trials that are currently   active. They will also help select the most qualified research   team to facilitate patient enrollment and improve the quality   and integrity of the data.

   Beyond the scope of clinical trials, there are a variety of   other qualified experts that can help create strategic alliances   with larger groups or pharmaceutical companies. It   is important to note that the choice of the right partner,   no matter what stage of drug development, can limit risk   and improve the chances of compound success. With the   right team and partners in place, early termination of a   trial for reasons other than patient safety does not necessarily   imply the end of the product. Strategic partnerships   and strong leadership can often turn around a situation   that was once considered a failure.

 There is no silver bullet to curing cancer, just as there is no  magic recipe for the success of a clinical trial. Every step  along the drug development journey brings specific results  that will contribute to the big picture and add to the advancement  of clinical research. Knowledge, rigor, leadership, good  judgment, open-mindedness, patient-centricity, and of course  strategic alliances are all critical components in achievingsmall victories towards enhancing patient outcomes.

 is a Lead Clinical Research Associate at Scimega Research Inc. She can be reached by e-mail at 

* is Director of Business Development at Scimega Research Inc. He can be reached by e-mail at 

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  *To whom all correspondence should be addressed.

http://appliedresearch.cancer.gov/tools/pro-ctcae.html


  2. Basch et al. Electronic toxicity monitoring and patient-reported
  outcomes. Cancer J. 2011; 17(4).

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