Abstract 309P
Background
ALP is the only α-selective PI3K inhibitor (i) and degrader approved for HR+, HER2–, PIK3CA-mut ABC. In SOLAR-1, ALP + FUL significantly prolonged PFS vs PBO + FUL in pts with HR+, HER2–, PIK3CA-mut ABC (HR 0.65, P=0.00065; median 11.0 vs 5.7 mo). Here, we describe post-progression ANP tx from SOLAR-1.
Methods
The SOLAR-1 study design was described previously (Andre et al, NEJM 2019). In this post-hoc, descriptive analysis of pts with HR+, HER2–, PIK3CA-mut ABC, 1st subsequent ANP tx were summarised into mutually exclusive groups: chemotherapy (CT)-based (CT ± other tx), hormonal therapy (HT)-based (HT ± other tx, except CT, CDK4/6i, or mTORi), and targeted therapy (TT; HT + CDK4/6i and HT + mTORi). Duration of 1st subsequent tx was summarised using the restricted mean survival time up to the maximum observed time in ALP or PBO, whichever comes first, post initiating 1st subsequent tx.
Results
The table shows 1st subsequent ANP tx as of the 23 April 2020 data cutoff. Rates and patterns of subsequent tx varied across regions. Median duration of CT-based, HT-based, and TT as 1st subsequent tx was 14.5 mo, 12.7 mo, and 11.4 mo in the ALP arm, and 14.4 mo, 11.6 mo, and 12.1 mo in the PBO arm, respectively. In the ALP arm, CT-based 1st subsequent tx was more frequent in pts with PFS ≤6 mo (56%, 30/54) than pts with PFS >6 mo (40%, 25/63). FUL and aromatase inhibitors (excluding FUL-containing regimens) were part of 1st subsequent tx in 21% (n=24) and 33% (n=39) of pts in the ALP arm, and 10% (n=14) and 38% (n=51) of pts in the PBO arm, respectively. Table: 309P
| All | Europe | N. America | Asia | Latin America | ||||||
| n (%)a | ALP (n=169) | PBO (n=172) | ALP (n=86) | PBO (n=87) | ALP (n=19) | PBO (n=24) | ALP (n=32) | PBO (n=38) | ALP (n=14) | PBO (n=17) |
| 1st subsequent therapyb | 117 (69) | 134 (78) | 54 (63) | 67 (77) | 14 (74) | 19 (79) | 24 (75) | 36 (95) | 10 (71) | 7 (41) |
| CT-based | 55 (47) | 74 (55) | 24 (44) | 44 (66) | 3 (21) | 8 (42) | 10 (42) | 15 (42) | 8 (80) | 6 (86) |
| HT-based | 31 (26) | 26 (19) | 15 (28) | 9 (13) | 5 (36) | 1 (5) | 9 (38) | 14 (39) | 1 (10) | 1 (14) |
| TT | 30c (26) | 31d (23) | 14 (26) | 11 (16) | 6 (43) | 10 (53) | 5 (21) | 7 (19) | 1 (10) | 0 |
aGiven small n’s, avoid comparisons.b1 and 3 pts in the ALP and PBO arms, respectively, received tx that could not be classified into these categories.cHT + CDK4/6i (n=15) and HT + mTORi (n=15).dHT + CDK4/6i (n=17) and HT + mTORi (n=14).
Conclusions
ALP + FUL does not seem to diminish the potential for benefit of subsequent ANP tx, including CT, HT, CDK4/6i, and mTORi. Together with the PFS benefit observed in SOLAR-1, this further supports the benefit of ALP + FUL in pts with HR+, HER2– PIK3CA-mut ABC.
Clinical trial identification
NCT02437318.
Editorial acknowledgement
We thank Amanda C. Vreeland, PhD, CMPP, of Healthcare Consultancy Group, LLC, for her medical writing assistance with this abstract, which was funded by Novartis Pharmaceuticals Corporation.
Legal entity responsible for the study
Novartis Pharmaceuticals Corporation.
Funding
Novartis Pharmaceuticals Corporation.
Disclosure
F. André: Financial Interests, Institutional, Funding, Speaker and Advisory fees: Roche; Financial Interests, Institutional, Funding, Speaker and Advisory fees: AstraZeneca; Financial Interests, Institutional, Funding, Speaker and Advisory fees: Daiichi Sankyo; Financial Interests, Institutional, Funding, Speaker and Advisory fees: Pfizer; Financial Interests, Institutional, Funding, Speaker and Advisory fees: Novartis; Financial Interests, Institutional, Funding, Speaker and Advisory fees: Eli Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Other, Travel fees: AstraZeneca; Financial Interests, Institutional, Other, Travel fees: GlaxoSmithKline; Financial Interests, Institutional, Other, Travel fees: Novartis; Financial Interests, Institutional, Other, Travel fees: Roche. H.S. Rugo: Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Novartis; Financial Interests, Institutional, Funding: Eli Lilly; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: OBI; Financial Interests, Institutional, Funding: Odonate; Financial Interests, Institutional, Funding: Daiichi Sankyo; Financial Interests, Institutional, Funding: Eisai; Financial Interests, Institutional, Funding: Seattle Genetics; Financial Interests, Institutional, Funding: MacroGenics; Financial Interests, Institutional, Funding: Sermonix; Financial Interests, Institutional, Funding: Immunomedics; Financial Interests, Personal, Other, Travel Support: Daiichi Sankyo; Financial Interests, Personal, Other, Travel Support: Mylan; Financial Interests, Personal, Other, Travel Support: Pfizer; Financial Interests, Personal, Other, Travel Support: Merck; Financial Interests, Personal, Other, Travel Support: AstraZeneca; Financial Interests, Personal, Other, Travel Support: Novartis; Financial Interests, Personal, Other, Travel Support: MacroGenics; Financial Interests, Personal, Other, Honoraria: Puma; Financial Interests, Personal, Other, Honoraria: Mylan; Financial Interests, Personal, Advisory Role, Consulting: Samsung. D. Juric: Financial Interests, Personal and Institutional, Other, Grants and personal fees: Novartis; Financial Interests, Personal and Institutional, Other, Grants and personal fees: Genentech; Financial Interests, Personal and Institutional, Other, Grants and personal fees: Eisai; Financial Interests, Personal and Institutional, Other, Grants and personal fees: EMD Serono; Financial Interests, Personal and Institutional, Other, Grants and personal fees: Syros; Financial Interests, Personal and Institutional, Other, Grants and personal fees: Petra Pharma; Financial Interests, Personal, Other, Personal fees: Ipsen; Financial Interests, Personal, Other, Personal fees: Vibliome; Financial Interests, Personal, Other, Personal fees: Relay Therapeutics; Financial Interests, Personal, Other, Personal fees: MapKure; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Celgene; Financial Interests, Institutional, Research Grant: Placon Therapeutics; Financial Interests, Institutional, Research Grant: InventisBio; Financial Interests, Institutional, Research Grant: Infinity Pharmaceuticals. G. Rubovsky: Financial Interests, Personal, Advisory Role, Consulting: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Advisory Board, participation in a data safety monitoring board or advisory board: Novartis; Financial Interests, Personal, Advisory Board, participation in a data safety monitoring board or advisory board: Roche. T. Yamashita: Financial Interests, Institutional, Funding: Chugai; Financial Interests, Institutional, Funding: Taiho; Financial Interests, Institutional, Funding: Nippon Kayaku; Financial Interests, Institutional, Funding: Kyowa Kirin; Financial Interests, Personal, Other, Lecture Fees: Chugai; Financial Interests, Personal, Other, Lecture Fees: Eisai; Financial Interests, Personal, Other, Lecture Fees: Novartis; Financial Interests, Personal, Other, Lecture Fees: Taiho; Financial Interests, Personal, Other, Lecture Fees: Nippon Kayaku; Financial Interests, Personal, Other, Lecture Fees: AstraZeneca; Financial Interests, Personal, Other, Lecture Fees: Kyowa Kirin; Financial Interests, Personal, Other, Lecture Fees: Pfizer Japan; Financial Interests, Personal, Other, Lecture Fees: Eli Lilly; Financial Interests, Personal, Other, Lecture Fees: Daiichi Sankyo. S.M. Stemmer: Financial Interests, Institutional, Other, Fee: Novartis; Financial Interests, Institutional, Research Grant: Teva; Financial Interests, Institutional, Research Grant: Clovis Oncology; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Can-Fite BioPharma; Financial Interests, Institutional, Research Grant: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: GEICAM; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Halozyme; Financial Interests, Institutional, Research Grant: BiolineRx; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Silenseed; Financial Interests, Institutional, Research Grant: Tiziana Life Sciences; Financial Interests, Institutional, Research Grant: CTG Pharma; Financial Interests, Institutional, Research Grant: Syncore; Financial Interests, Institutional, Research Grant: Moderna Therapeutics; Financial Interests, Institutional, Research Grant: Exelixis; Financial Interests, Institutional, Research Grant: Rafael Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Canfite; Financial Interests, Personal, Stocks/Shares: Tyrnovo; Financial Interests, Personal, Stocks/Shares: CTG Pharma; Financial Interests, Personal, Stocks/Shares: VYPE; Financial Interests, Personal, Stocks/Shares: DocBoxMD; Financial Interests, Personal, Royalties, patents, royalties, and other intellectual property in combo patent, check point inhibitors: CTG Pharma; Financial Interests, Personal, Royalties, patents, royalties, and other intellectual property in combo patent, check point inhibitors: VYPE. Y. Lu: Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Advisory Role, consulting fees: Novartis; Financial Interests, Personal, Advisory Role, consulting fees: MSD; Financial Interests, Personal, Advisory Role, consulting fees: Pfizer; Financial Interests, Personal, Advisory Role, consulting fees: Eli Lilly; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other, Travel/meeting fees: Roche; Financial Interests, Personal, Other, Travel/meeting fees: Pfizer; Financial Interests, Personal, Other, Travel/meeting fees: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other, supply of drug for clinical trial: Pfizer. M.K. Miller, I. Lorenzo: Financial Interests, Personal, Full or part-time Employment: Novartis; Financial Interests, Personal, Stocks/Shares: Novartis. H. Hu: Financial Interests, Personal, Full or part-time Employment: Novartis. E.M. Ciruelos: Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Other, Travel/ Accommodation/Expenses: Pfizer; Financial Interests, Personal, Other, Travel/ Accommodation/Expenses: Roche.