BETHESDA, MdThe Food and Drug Administrations Oncologic Drugs Advisory Committee (ODAC) has recommended approval of QLT Photo-Therapeutics Photofrin (porfimer sodium) for use as photodynamic therapy (PDT) of T1 stage endobronchial carcinoma in patients with non-small-cell lung cancer (NSCLC) for whom surgery and radiotherapy are not indicated.
The committee gave its favorable vote after first refusing to recommend approval of Photofrin for a broader group of patientsall those with partially or completely obstructed endobronchial non-small-cell lung cancer.
For the more restrictive usage, which did win the ODACs backing, QLT PhotoTherapeutics had sought Photofrins use in microinvasive NSCLC. Julia G. Levy, PhD, ScD, the companys president and chief executive officer, later explained that microinvasive meant tumors of shallow depth. We think it is a better description of what we can treat, she said.
Committee members, however, expressed concern that microinvasive was too imprecise and not a term commonly used by oncologists treating lung cancer. They voted, instead, to recommend the drugs use in T1 tumors, which by definition are no larger than 3 cm. Nonetheless, the ODAC panel recommended that, in the prescribing information, the FDA consider limiting the size of the NSCLC tumors that could be treated with Photofrin to somewhat less than 3 cm.
Should the drug be approved as recommended, Dr. Levy said, the treatment would be applicable for use in perhaps 15,000 patients in the United States each year.
The FDA approved Photofrin in 1995 for palliative use in esophageal cancer. The drug is approved in Canada for esophageal and bladder cancer; for lung and esophageal cancer in France and Holland; for early stage lung cancer in Germany; and for several cancers in Japan, including lung, gastric, and early stage cervical cancer.
Photofrin is unique in its mechanism of action in that it requires light to activate its anticancer activity. It is given intravenously and taken up selectively by tumor cells. After a period of time, when the drug has had time to largely clear from normal tissue, a specific dose of a specific wavelength of light is shined on the tumor area. In lung cancer, the light is generated by a laser and delivered via a fiberoptic strand. The light and drug interact to create a highly reactive form of oxygen that kills the cancer cells.
To support Photofrins approval for use in superficial NSCLC in patients who cannot undergo surgery and radiation, QLT PhotoTherapeutics submitted data from a total of 102 patients treated in three investigator-initiated trials that were not sponsored by the company.
The trial participants were 90% male, with a median age of 64. Of the 102 patients, both surgery and radiation were contraindicated in 24, who were designated the indication group.
In presenting data from the three trials on behalf of QLT PhotoTherapeutics, Eric Edell, MD, associate professor of medicine at the Mayo Medical School, said that 79% of the overall total and 92% of the indication group had a complete response. One death occurred within 30 days of treatment.
Thirty-five of the patients had a recurrence of their cancer. Median time to recurrence was 2.8 years in the overall group and 2.7 years in the indication group. Median survival was quite similar in the two groups as well3.5 years in the group of 102 patients and 3.4 years in the indication group of 24. Median disease-specific survival was 5.7 years in the overall group and could not be calculated for the indication group.
Severe events occurred in 6% of patients, mostly from photosensitivity caused by the drug, and 5% suffered life-threatening events, mostly pulmonary.
FDA reviewer Grant Williams, MD, noted that in one of the three investigator studies, 94% of the 32 patients experienced some form of adverse event. I have some suspicion the adverse event rate was higher in the other studies than reported, he told the ODAC panel.
While expressing concern about the potential for life-threatening lung complications observed in the three Photofrin trials, particularly hemoptysis and respiratory insufficiency, ODAC committee members also noted that NSCLC patients contraindicated for surgery or radiation have no other treatment available to them. The panel voted 9 to 0, with one abstention, to recommend the drugs approval for T1 tumors in such patients.
This is the first time that photodynamic therapy has been recommend for approval for a curative intent in the United States, said Mohammed Azab, MD, the companys vice president for clinical research and medical affairs.
Dr. Levy said that the company will continue working with the FDA in order to win approval for Photofrin for the reduction and palliation of symptoms in patients with completely or partially obstructing endobronchial non-small-cell lung cancer.