The role of PDT with PHOTOFRIN® (porfimer sodium) for injection¹

PHOTOFRIN® is indicated for the reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial NSCLC.

Potential patient types include those with an obstructing lesion in an area that is accessible to bronchoscopy.

Clinically significant benefits demonstrated

Two randomized, multicenter Phase III trials comparing the safety and efficacy of PHOTOFRIN® to Nd:YAG laser therapy were conducted to assess:

• Objective tumor response
• Improvement in atelectasis in patients with atelectasis at baseline

Objective tumor response^1,†

CR+PR where CR = complete response (absence of bronchoscopically visible tumor) and PR = partial response (increase of >=50% in the smallest luminal diameter; or any appearance of a lumen for completely obstructing tumors).

 

Note: Data based on 2 randomized multicenter Phase III studies that compared the safety and efficacy of PHOTOFRIN® PDT versus Nd:YAG laser therapy for reduction of obstruction and palliation of symptomatic patients with partially or completely obstructing endobronchial non-small-cell lung cancer. A course of PDT therapy consisted of one injection of PHOTOFRIN® (2 mg/kg administered as a slow intravenous injection over 3 to 5 minutes) followed by up to 2 non-thermal applications of 630 nm laser light. Light doses of 200 J/cm of diffuser length were used. Primary measures of efficacy were objective tumor response and improvement in atelectasis in patients with atelectasis at baseline. Assessments were made at Week 1 and at monthly intervals after treatment. This graph shows the results from all randomized patients in the two studies combined (PDT group: N=102; Nd:YAG group: N=109). Objective tumor response rates were: 59% for PDT and 58% for Nd:YAG at Week 1; 60% for PDT and 41% for Nd:YAG at Month 1 or later.

^†Statistical comparisons were precluded by the amount of missing data at Month 1 or later. For tumor response, PDT 28% missing; Nd:YAG 38% missing. Objective tumor response included both complete response (CR) and partial response (PR). CR is defined as the absence of a bronchoscopically visible tumor. PR is defined as an increase of ≥50% in the smallest luminal diameter, or for completely obstructing tumors, any appearance of a lumen.¹

Atelectasis improvement in patients with atelectasis at baseline^1,†

Clinically significant symptom improvement in patients with dyspnea^1,†,¶

Patients with moderate to severe symptoms at baseline.

^¶Graded on a 6-point severity rating scale. Clinically significant symptom improvement was defined as a change of ≥2 grades from baseline.¹

Clinically significant symptom improvement in patients with cough^1,†,§

^§Graded on a 5-point severity rating scale. Clinically significant symptom improvement was defined as a change of =/> 2 grades from baseline.

Clinically significant symptom improvement in patients with hemoptysis^1,†,§

^§Graded on a 5-point severity rating scale. Clinically significant symptom improvement was defined as a change of ≥2 grades from baseline.

Clinically significant symptom improvement in patients with any symptom^1,†

^§Clinically significant symptom improvement was defined as a change of ≥2 grades from baseline.

Note: Data based on two randomized multicenter Phase III studies that compared the safety and efficacy of PHOTOFRIN® PDT versus Nd:YAG laser therapy for reduction of obstruction and palliation of symptomatic patients with partially or completely obstructing endobronchial non-small-cell lung cancer. A course of PDT therapy consisted of one injection of PHOTOFRIN® (2 mg/kg administered as a slow intravenous injection over 3 to 5 minutes) followed by up to 2 non-thermal applications of 630 nm laser light. Light doses of 200 J/cm of diffuser length were used. Primary measures of efficacy were objective tumor response and improvement in atelectasis in patients with atelectasis at baseline. Assessments were made at Week 1 and at monthly intervals after treatment.

^†Statistical comparisons were precluded by the amount of missing data at Month 1 or later.

Adverse Reactions Reported in >=5% of Patients with Obstructing Endobronchial Cancer

Note: Source PHOTOFRIN® (porfimer sodium for injection) [package insert]

• Clinically significant symptom improvement^1,†The incidences of bronchitis and dyspnoea were higher with PDT than with Nd:YAG. Most cases of bronchitis occurred within 1 week of treatment and all but 1 were mild or moderate in intensity. Treatment-related worsening of dyspnoea is generally transient and self-limiting¹
• Life-threatening respiratory insufficiency likely due to therapy occurred in 3% of PDT-treated patients and 2% of Nd:YAG-treated patients¹

There was a trend toward a higher rate of fatal massive hemoptysis (FMH) occurring on the PDT arm (10%) versus the Nd:YAG arm (5%), however, the rate of FMH occurring within 30 days of treatment was the same for PDT and Nd:YAG (4% total events, 3% treatment-associated events).

Patients who have received radiation therapy have a higher incidence of FMH after treatment with PDT and after other forms of local therapy than patients who have not received radiation therapy, but analyses suggest that this increased risk may be due to associated prognostic factors such as having a centrally located tumor

• The incidence of FMH in patients previously treated with radiotherapy was 21% (6/29) in the PDT group and 10% (3/29) in the Nd:YAG group
• In patients with no prior radiotherapy, the overall incidence of FMH was less than 1%

Important Safety Information and Indication

Contraindications

• PHOTOFRIN® is contraindicated in patients with porphyria
• Photodynamic Therapy (PDT) is contraindicated in patients with an existing tracheoesophageal or bronchoesophageal fistula
• PDT is contraindicated in patients with tumors eroding into a major blood vessel
• PDT is not suitable for emergency treatment of patients with severe acute respiratory distress caused by an obstructing endobronchial lesion because 40 to 50 hours are required between injection with PHOTOFRIN® and laser light treatment
• PDT is not suitable for patients with esophageal or gastric varices, or patients with esophageal ulcers >1 cm in diameter

Warnings and Precautions

• Tracheoesophageal or bronchoesophageal fistula can occur if esophageal tumor is eroding into trachea or bronchial tree
• Gastrointestinal perforation can occur
• High risk of bleeding in patients with esophageal varices
• High risk for fatal massive hemoptysis with endobronchial tumors that are: large, centrally located; cavitating; extensive, extrinsic to the bronchus
• After treatment of high-grade dysplasia (HGD) in Barrett’s esophagus (BE), monitor endoscopic biopsy every three months, until four consecutive negative evaluations for HGD have been recorded
• Photosensitivity can be expected; ocular sensitivity is possible
• Allow 2-4 weeks between PDT and subsequent radiotherapy
• Substernal chest pain may occur after treatment
• Treatment induced inflammation can cause airway obstruction. Administer with caution to patients with tumors in locations where treatment-induced inflammation can obstruct the main airway
• Esophageal stenosis occurs frequently after treatment of HGD in BE
• Patients with hepatic or renal impairment may need longer precautionary measures for photosensitivity
• Thromboembolic events can occur following photodynamic therapy with PHOTOFRIN®
• Embryo-Fetal Toxicity: May cause embryo-fetal toxicity. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

Adverse Reactions

Most common adverse reactions reported during clinical trials (>10% of patients) are:

• Esophageal Cancer: Anemia, pleural effusion, pyrexia, constipation, nausea, chest pain, pain, abdominal pain, dyspnoea, photosensitivity reaction, pneumonia, vomiting, insomnia, back pain, pharyngitis
• Obstructing Endobronchial Cancer: Dyspnoea, photosensitivity reaction, hemoptysis, pyrexia, cough, pneumonia
• Superficial Endobronchial Tumors: Exudate, photosensitivity reaction, bronchial obstruction, edema, bronchostenosis
• High-Grade Dysplasia in Barrett’s Esophagus: Photosensitivity reaction, esophageal stenosis, vomiting, chest pain, nausea, pyrexia, constipation, dysphagia, abdominal pain, pleural effusion, dehydration

These are not all the possible side effects of PHOTOFRIN®. For more information call your healthcare provider. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088 or call Pinnacle Biologics, Inc. at 1-866-248-2039.

PHOTOFRIN® is indicated for:

Esophageal Cancer

• Palliation of patients with completely obstructing esophageal cancer, or of patients with partially obstructing esophageal cancer who, in the opinion of their physician, cannot be satisfactorily treated with Nd:YAG laser therapy

Endobronchial Cancer

• Treatment of microinvasive endobronchial non-small-cell lung cancer (NSCLC) in patients for whom surgery and radiotherapy are not indicated
• Reduction of obstruction and palliation of symptoms in patients with completely or partially obstructing endobronchial NSCLC

High-Grade Dysplasia in Barrett’s Esophagus

• Ablation of high-grade dysplasia in Barrett’s esophagus patients who do not undergo esophagectomy

Please see accompanying full Prescribing Information for Photofrin®

References: 1. PHOTOFRIN® (porfimer sodium for injection) [package insert]. Bannockburn, IL: Pinnacle Biologics.