The BEACON Study (Breast Cancer Outcomes With NKTR-102)

Duration of OS was defined as the time from the date of randomisation to the date of death due to any cause. Subjects were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. OS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. Subjects who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Subjects who did not have any follow-up since the date of randomization were censored at the date of randomization.

Time frame: 36 Months

The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms.

Time frame: Up to 38 months.

Population: 429 (ITT Population) 423 (ITT Population)

CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (≥ 182 days).

Time frame: Up to 38 months.

DOR was defined as the time from first documented CR or PR until the earliest evidence of disease progression or death from any cause. Subjects who were alive without documented disease progression per RECIST version 1.1 were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease.

Time frame: Up to 38 months.

Population: The population analyzed for this outcome measure solely comprised of patients who achieved CR or PR per RECIST.

Proportion of subjects who had a reduction in dose.

Time frame: Up to 38 months.

PFS was defined as the time from the date of randomization to the earliest date of disease progression (assessed by the investigator according to RECIST version 1.1) or death due to any cause. PFS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. For subjects whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For subjects who received new anti-cancer therapy, the PFS time was censored at the start of the new anti-cancer therapy.

Time frame: Up to 38 months.

ORR was defined as the proportion of subjects with a complete response (CR) or a partial response (PR), assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 The analyses were performed for subjects in the efficacy evaluable population who had measurable disease as determined by the investigator at baseline.

Time frame: Up to 38 months.

Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean t½ values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. The t½ of all analytes was primarily driven by NKTR-102. Thus, the NKTR-102 t½ of 37 days also applies to all NKTR-102 metabolites.

Time frame: Up to 38 months.

Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean Cmax values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.

Time frame: Up to 38 months.

Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population pharmacokinetic (PK) model-derived mean AUC values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution.

Time frame: Up to 38 months.

The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhea, constipation, insomnia and dyspnea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (from 1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms.

Time frame: From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.

Population: 429 (ITT Population) 423 (ITT Population)

The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items to assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms.

Time frame: Baseline

Population: 429 (ITT Population) 423 (ITT Population)

The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhoea, constipation, insomnia and dyspnoea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms.

Time frame: Up to 39 months

Population: 429 (ITT Population) 423 (ITT Population)