Topotecan Hydrochloride (Page 5 of 6)

14.2 Small Cell Lung Cancer (SCLC)

The efficacy of topotecan hydrochloride for injection was evaluated in 426 patients with recurrent or progressive small cell lung cancer (SCLC) in a randomized, comparative trial and in 3 single-arm trials.

Randomized Comparative Trial

In a randomized, comparative trial, 211 patients were randomized 1:1 to receive topotecan hydrochloride for injection (1.5 mg/m² once daily intravenously for 5 days starting on Day 1 of a 21-day cycle) or CAV (cyclophosphamide 1,000 mg/m² , doxorubicin 45 mg/m² , vincristine 2 mg administered sequentially on Day 1 of a 21-day cycle). All patients were considered sensitive to first-line chemotherapy (responders who then subsequently progressed greater than or equal to 60 days after completion of first-line therapy). A total of 77% of patients treated with topotecan hydrochloride for injection and 79% of patients treated with CAV received platinum/etoposide with or without other agents as first-line chemotherapy. The efficacy outcome measures were overall response rate, response duration, time to progression or OS.

The results of the trial did not show statistically significant improvements in response rate, response duration, time to progression, or OS as shown in Table 5.

Table 5. Efficacy Results in Patients With Small Cell Lung Cancer Sensitive to First-Line Chemotherapy in Study 090

P arameter	Topotecan Hydrochloride for Injection ( n = 107)	CAV b ( n = 104)
Overall response rate (95% CI)	24% (16%, 32%)	18% (11%, 26%)
Complete response rate	0%	1%
Partial response rate	24%	17%
Re sponse duration a ( m onths) Median (95% CI)	3.3 (3, 4.1)	3.5 (3, 5.3)
Time to progression (months)	3.1 (2.6, 4.1) 2.8 (2.5, 3.2)
Median (95% CI)
Hazard ratio (95% CI)	0.92 (0.69, 1.22)
Overall survival (months)	5.8 (4.7, 6.8) 5.7 (5, 7)
Median (95% CI)
Hazard ratio (95% CI)	1.04 (0.78, 1.39)

Abbreviations: CI, confidence interval.

^a The calculation for duration of response was based on the interval between first response and time to progression.

^b CAV = cyclophosphamide, doxorubicin and vincristine.

The median time to response was similar in both arms: topotecan hydrochloride, 6 weeks (2.4 weeks to 3.6 months) versus CAV, 6 weeks (5.1 weeks to 4.2 months).

Changes on a disease-related symptom scale are presented in Table 6. It should be noted that not all patients had all symptoms, nor did all patients respond to all questions. Each symptom was rated on a 4-category scale with an improvement defined as a change in 1 category from baseline sustained over 2 courses. Limitations in interpretation of the rating scale and responses preclude formal statistical analysis.

Table 6. Symptom Improvement^a in Patients With Small Cell Lung Cancer in Study 090

Symptom	Topotecan Hydrochloride for Injection (n = 107)		CAV ( n = 104)
	n b	( % )	n b	( % )
Shortness of breath	68	28	61	7
Interference with daily activity	67	27	63	11
Fatigue	70	23	65	9
Hoarseness	40	33	38	13
Cough	69	25	61	15
Insomnia	57	33	53	19
Anorexia	56	32	57	16
Chest pain	44	25	41	17
Hemoptysis	15	27	12	33

^a Defined as improvement sustained over at least 2 courses compared with baseline.

^b Number of patients with baseline and at least 1 post-baseline assessment.

Single-Arm Trials

Topotecan hydrochloride for injection was also studied in three open-label, non-comparative trials (Studies 014, 092 and 053) in a total of 319 patients with recurrent or progressive SCLC after treatment with first-line chemotherapy. In all three trials, patients were stratified as either sensitive (responders who then subsequently progressed greater than or equal to 90 days after completion of first-line therapy) or refractory (no response to first-line chemotherapy or who responded to first-line therapy and then progressed within 90 days of completing first-line therapy). Response rates ranged from 11% to 31% for sensitive patients and 2% to 7% for refractory patients. Median time to progression and median survival were similar in all three trials and the comparative trial.