Trial Outcomes & Findings for Retrospective Chart Review Study of Patients With PIK3CA-Related Overgrowth Spectrum Who Have Received Alpelisib (NCT NCT04285723)

Participants were from Australia (1), France (50), Ireland (1), Spain (3) and United States (2)

Retrospective Chart Review Study of Patients With PIK3CA-Related Overgrowth Spectrum Who Have Received Alpelisib

Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions.

Percent change in the sum of measurable target lesion (1 to 3 lesions) volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date: (baseline) was defined as the date of alpelisib initiation End of study: patients were followed up to a maximum of 187 weeks.

Percent change in the sum of all measurable (target and non-target) lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation. End of study: patients were followed up to a maximum of 187 weeks As no measurable non-target lesions were identified, the results for changes in the sum of all measurable (target and non-target) lesion volume were identical to the results presented for measurable target lesion.

Percent change in the sum of all measurable non-target lesion volume, as assessed by a central review of imaging scans, as measured by the change between the index date (or up to 24 weeks prior) and key time-points following the index date. The index date (baseline) was defined as the date of alpelisib initiation.

Duration of response is defined as the time from first documented response, to the date of the first documented disease progression or death due to any cause. Response is defined by achieving at least 20% reduction from index date in the sum of measurable target lesion volume (1 to 3 lesions, via central review of imaging scans), provided that none of the individual target lesions have ≥ 20% increase from index date and in absence of progression of non-target lesions and without new lesions. Disease progression is defined as an increase of any individual target lesions of ≥ 20% in volume from previous assessment, progression of non-target PIK3CA Related Overgrowth Spectrum (PROS) lesions or appearance of a new PROS lesion.

Number of participants with concomitant PIK3CA Related Overgrowth Spectrum (PROS)-related non-drug treatments and other medical interventions by reason for discontinuation. A patient may have multiple information, but was counted only once in type of other supportive non-drug treatment if more than one type in this category has been reported.

Number of participants with at least one concomitant utilization of PIK3CA Related Overgrowth Spectrum (PROS)-related medication. End of study: patients were followed up to a maximum of 187 weeks. Results are provided for the full study population as planned and documented in the protocol and SAP, and not by age group.

Number of surgeries by reason of surgery. A patient may have multiple anatomical sites of surgery and types of surgery on the same day.

Improvement in PIK3CA Related Overgrowth Spectrum (PROS) signs and symptoms was defined based on Common Toxicity Criteria (CTC) grade reduction or resolution of the event from index date. CTC is a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy. The Common Terminology Criteria for Adverse Events (CTCAE) system is a product of the US National Cancer Institute (NCI). For this study, version 4.03 was used

Participants with a change in performance status score (ECOG, Karnofsky, Lansky) between the index date and week 24. Patients completed one questionnaire (ECOG, Karnofsky or Lansky) based on physicians choice. The Eastern Cooperative Oncology Group (ECOG) score runs from 0 to 5, with 0 denoting perfect health and 5 death. The Karnofsky Performance Score (KPS) and Lansky score run from 0 to 100, where 0 is death and 100 is perfect health. For the ECOG scale, "improvement" is defined as a decrease by at least 1 point and and "worsening" is defined as an increase by at least 1 point. For the Karnofsky and Lansky scale, "improvement" is defined as an increase by at least 20 points and worsening is defined as a decrease by at least 20 points. If neither of the criteria for improvement or worsening is met, then it is considered stable.

Change in functional status: Mobility severity assessment measured up to the judgment of the investigator. A patient may have multiple information

Change in functional status: School status during the study period (no attendance, part-time or full time). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" as well as , "Part-time" or "No attendance" to "Full-time"; Worsening is defined as a shift from reporting of "Part-time" to "No attendance", as well as from "Full-time" to "Part-time" or "No attendance". If neither of the criteria for improvement or worsening is met, then it is considered stable.

Change in functional status: Work status assessment during the study period (no attendance, part-time, full-time or unemployed). Improvement is defined as a shift from reporting of "No attendance" to "Part-time" or "Full time", from "Part-time" to "Full-time", as well as from "Unemployed" to "Part-time" or "Full-time" work. Worsening is defined as a shift from reporting of "Part-time" to "No attendance", "Full-time" to "Part-time" or "No attendance" as well as "Part-time" or "Full-time" to "Unemployed" status. Change in score is only applicable if both index date and post-index date information are available. If a patient has more than 1 score reported within the same time window, the worst is considered. If neither of the criteria for improvement or worsening is met, then it is considered stable.

Hospitalizations starting on or after the start of study treatment (index date) or starting prior to and continuing after the start of study treatment are summarized.

Worst post-index date hematology abnormalities based on Common Toxicity Criteria (CTC) grades during the study period. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized.

Worst post-index date biochemistry abnormalities based on Common Toxicity Criteria (CTC) grades. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated. Patients are counted only for the worst grade observed post-index date values. Laboratory assessments performed more than 30 days after last study treatment administration date are not summarized.

Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥95th percentile of the age and height group Low Systolic blood pressure: ≤5th percentile of the age and height group. High diastolic blood pressure: ≥95th percentile of the age and height group Low diastolic blood pressure: ≤5th percentile of the age and height group. High pulse rate (bpm): 2-3 years: \>128; 3-4 years: \>123; 4-6 years: \>117; 6-8 years: \>111; 8-12years: \>103; 12-15 years: \>96; ≥15 years: \>92 Low pulse rate (bpm): 2-3 years: \<92; 3-4 years: \<86; 4-6 years: \<81; 6-8 years: \<74; 8-12 years: \<67; 12-15 years: \<62; ≥15 years: \<58. High weight: increase from baseline of ≥2 Body mass index (BMI) for age percentile categories Low weight: decrease from baseline of ≥2 BMI-for-age percentile categories

Low/High: Indicating abnormal value/change from index date. High systolic blood pressure: ≥180 mmHg and increase ≥20 mmHg Low systolic blood pressure: ≤90 mmHg and decrease ≥20 mmHg. High diastolic blood pressure: ≥105 mmHg and increase ≥15 mmHg Low diastolic blood pressure: ≤50 mmHg and decrease ≥15 mmHg. High pulse rate: ≥120 bpm and increase ≥15 bpm Low pulse rate: ≤ 50 bpm and decrease ≥15 bpm. High weight: Increase ≥10% Low weight: Decrease ≥10%

Notable Electrocardiogram (ECG) values during the study period

Assessed in patients who were aged \<18 years at the time of alpelisib initiation. SDS (standard deviation scores) for height and BMI are obtained from the WHO Growth Charts, and SDS for height and weight velocity are obtained from Baumgartner et al. (1986). Height or weight velocity is a variable derived from the measurement of height or weight at different times and represents the increase in height or weight during a fixed period. SD- scores are used to describe how far a measurement is from the median (average). Weight-for-age reference data are not available beyond age 10.

A patient with multiple severity grades for an AE is only counted under the maximum grade. All grades includes any AEs with missing grade. Grade refers to the severity of the AE: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 Life-threatening consequences; urgent intervention indicated.