Respectfully disagree, we have also quite some examples of huge PFS improvement with OS detriment. Detriment, not even no effect, but pernicious effect. Examples: PI3K inhibitors in CLL/FL, venetoclax in MM. Can't guarantee you're benefiting patients just because PFS is extended (@Ivaj960612)

#Ipatasertib plus #rucaparib has a manageable safety profile but did not show synergistic or additive antitumor activity in previously treated patients with #mCRPC. @jorgedgallo3 @HowardGurney https://t.co/uS8fdu1XcX (@CCR_AACR)

The #FDA has granted fast track designation to the combination of paxalisib & radiation for patients with brain metastases originating from a primary tumor. #bcsm | @JYangMDPhD @uwradonc @fredhutch https://t.co/EQPVfbNvYe (@TargetedOnc)

Hoping breast cancer treatment with alpelisib will be quickly studied for possible synergy (synthetic lethality or ?) with PARPi early or at PIK3i resistance emergence due to new alterations in DNA repair genes evolving. Ovarian cancer racing ahead with this. Thanks. (@nursekristinrn)

Still no role for targeting PI3K pathway in mCRPC – @AzadOncology #antitumor #cancer #clinicalresearch #ipatasertib #oncology #oncodaily https://t.co/xOYDsLgQTQ (@oncodaily)

Gedatolisib + palbociclib & letrozole produced durable responses w/ comparable safety to that observed w/ palbociclib & letrozole alone in treatment-naïve patients withER-positive, HER2-negative advanced breast cancer @hoperugo @UCSFCancer #bcsm https://t.co/Hpc5ZFF5GJ (@OncLive)

Gedatolisib + palbociclib & letrozole produced durable responses w/ comparable safety to that observed w/ palbociclib & letrozole alone in treatment-naïve patients withER-positive, HER2-negative advanced breast cancer @hoperugo @UCSFCancer #bcsm https://t.co/D5Xk9qw1X0 (@OncLive)

Gedatolisib Triplet Shows Early Efficacy in Previously Untreated ER+/HER2– Breast Cancer @hoperugo @UCSFCancer #bcsm https://t.co/WeZVEnULVD (@OncLive)

Brilliant presentation by N Turner @royalmarsdenNHS on CDK4/6 inhibition for ER+ #breastcancer at #ASCO23 ▶️Abema is SOC in the adj setting ▶️Ribo or Abema are SOC in the palliative setting ▶️Post CDK alpelisib & capivasertib active also after short PFI on CDK #bcsm (@nicolobattisti)

Yes, we were scooped but incredible control of profound hypoglycemia in a patient with metastatic insulinoma on a D30 drip, glucagon drip, dex, starch. Now on single agent PIQRAY and has an ECOG of 0-1 off all other meds and with rising A1C. (@Labrat3)

That is a very interesting case report, alpelisib in non–islet-cell tumor hypoglycemia (NICTH). I wonder if anyone has tried this in refractory hypoglycemia in malignant insulinoma where regional therapy is not feasible. Anyone? Anyone? Bueller...? https://t.co/gIgkfRWzo2 (@OncoThor)

The abstract of one of our two #AACR23 #lymphoma posters. @IOR_Bellinzona @USI_en @EnteOspedaliero @CascioneLuciano @AnastasiosStat2 @ManelEsteller ERBB4 as resistance to BTK and PI3K inhibitors in lymphomas: https://t.co/amUYwAoaWn (@frbertoni)

Just in time for #AACR23 👉The emerging role of PI3K inhibitors for solid tumour treatment and beyond has been published in @BrJCancer @curijoey @PTarantinoMD @OncoAlert 👉The advent of allosteric mutant and isoform selective PIK3CA inhibitors, some of which are currently… https://t.co/MKDA91tYLa (@VivekSubbiah)

Giudetti et al • Emavusertib - IRAK4i • IRAK4 downstream of TLR • MZL lines: myd88 L265P conferred sensitivity to Emavusertib • improved sens to combos with PI3Ki / BTKi even when secondary resistance to these agents seen. #lymsm https://t.co/N7TzEupOkd (@graham74GC)

We previously showed that breast tumors with multi-PIK3CA mutations correlate with increased PI3Ki sensitivity. Our pan-tumor study provides new insights into the genetic heterogeneity and tissue specificities of multi-PIK3CA mutations, to guide PI3Ki strategies in the clinic. (@NeilVasan)

🎥 @hoperugo of @UCSFCancer talks on BYLieve Study Cohort A: alpelisib + ET in PIK3CA-mutant, HR+, HER2-, advanced breast cancer Watch: 👉https://t.co/Y1SYVz4giP👈 @SABCSSanAntonio #SABCS22 #BCSM #BreastCancer (@VJOncology)

Large retrospective study on histology-based PFS/OS of #ILC vs #IDC HR+ MBC tx w/ CDK4/6i, mTORi, or PI3Ki + ET.. @MDAndersonNews. “These results are reassuring for patient with lobular and mixed histologies,” @JAMouabbi #bcsm #Lobular #BreastCancer (@JaniceTNBCmets)

🔥📰 Our @MDAndersonNews 📝 just published in @Nature_NPJ looking at histology-based (#ILC vs IDC) outcomes (PFS, OS) in HR+ metastatic #breast_cancer treated with CDK4/6is, mTORi or PI3Ki + ET #bcsm #EndCancer https://t.co/ezJZ7yZu8G (@JAMouabbi)

In CALGB 40601 PIK3CA mutations were predictive and prognostic, driven by luminal subtype esp LumB - work by Paola Zagami. In same poster discussion, intriguing early data of adding PI3Ki MEN1611 to anti HER2 Rx by Martine Piccart. @UNCBreastSPORE #SABCS22 @ALLIANCE_org (@DrLisaCarey)

The effect by Zilovertamab is double: 1. introduce the MMAE molecule into the lymphomatous cell. 2. inhibit the PI3K/AKT/mTOR pathway via ROR1. (@hematologo)

10/17 #TumorBoardTuesday #BreastCancer 📆When is the ideal time to test for PIK3CA mutation❓ 🧪Test in HR+ MBC at diagnosis or after CDK4/6i progression 🔸BYLieve cohort A: 👉🏽 alpelisib benefit after CDK4/6i+AI (median PFS 7.3 mo) 📚@hoperugo https://t.co/AyZcHmCDGz (@JasmineSukumar)

ARID1A-deficient bladder cancers are sensitive to combination therapies with the EZH2 inhibitor and inhibitors of PI3K. https://t.co/cImqZpoRtO @JedUro1, @darshan_sc, @UABPathology, @UABUrology, @ONealCancerUAB, @UABHeersink, @DrNetto, @sonpavde, @BCAN_Research, @Now_UALCAN (@Varambally_S)

JCI Insight - ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors https://t.co/iNAybzqCPr (@weldeiry)

ARID1A-Deficient Bladder Cancer Is Dependent on PI3K Signaling and Sensitive to EZH2 and PI3K Inhibitors | comment: Isabella Stelter https://t.co/Im6CLMz1zk via @practiceupdate. @JedUro1, @DrNetto, @BladderCancerUS, @UABHeersink,@sonpavde, @ONealCancerUAB, @UABPathology,#Cancer (@Varambally_S)

Our study "ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors". Appeared in JCI Insight. https://t.co/pFnXfR4aub @JedUro1, @sonpavde, @DrNetto, @UABHeersink, @ONealCancerUAB, @UABPathology, @UABUrology, @darshan_sc, #Cancer (@Now_UALCAN)

Thrilled to share our study "ARID1A-deficient bladder cancer is dependent on PI3K signaling and sensitive to EZH2 and PI3K inhibitors". From JCI Insight. https://t.co/d3kLEryKKi @sonpavde, @DrNetto, @UABHeersink, @ONealCancerUAB, @UABPathology,@BladderCancerUS, @UABUrology (@Varambally_S)

NICE approves two treatment options for advanced breast cancer https://t.co/MraoHvwr6i Alpelisib first targeted treatment for patients with PIK3CA mutation found in 30-40% of oestrogen receptor positive HER2 negative breast cancers @DrIanWeissman @SusanChubb1 @SirGeoffPalmer (@Nigelj08223326)

As our Melanoma and Skin Section Editor @jasonlukemd presents at #ASCO22, revisit his paper on a first-in-human trial of the PI3Kβ-selective inhibitor SAR260301 in patients with advanced solid tumors https://t.co/iOzwBoZXge @OncoAlert (@JournalCancer)

SOLAR-1 alpelisib update takeaway: 📍Targeting activating PIK3CA mutations WORKS. 📍We need to test & treat! #ASCO22 #bcsm (@DrSGraff)

Alpelisib is the only small-molecule PI3Kα inhibitor approved by the FDA for the treatment of patients with metastatic breast cancer with mutated PIK3CA2. However, medication is often associated with a lack of durable responses and substantial on-target but off-tumor toxicities. (@PerceptronMD)

The name looked familiar! @GRASPtweets will review @JAMouabbi’s #ASCO22 poster “Survival outcomes in metastatic HR+/HER2 IDC compared to ILC & mixed ductal/lobular treated w endocrine therapy in combo with CDK4/6, mTOR, or PI3K inhibitors. GRASP registration opens soon! #BCSM (@christeeny513)

WATCH: Experts give takeaways from a discussion on best practices treating HR+/HER2- metastatic breast cancer with CDK4/6 inhibitors and PI3K therapies based on data presented at #ESMO21 @Neil_Iyengar @BCJoyceO @drsarahsam @DukeCancer @sloan_kettering https://t.co/oahGzWRWK8 (@OncLive)

The open-label, multicentric phase 2 SAFIR02_BREAST and SAFIR-PI3K trials enrolled patients with HER2-negative metastatic breast cancer who were eligible for first- or second-line chemotherapy. @FAndreMD @GustaveRoussy @SABCSSanAntonio #SABCS21 #bcsm https://t.co/JtdxIcskyP (@OncLive)

Targeting KRAS mutant lung cancer: light at the end of the tunnel. Interesting, another @BarbaDelCid collaboration inhibiting cRAF #RAF1 shows early strong signal in #KRAS G12V #NSCLC (RAMP202), @udai_banerji (FRAME) with 57% RR. #cRAF #MEK #SOS #SHP2 #FAK #Pi3K #mTOR https://t.co/PIYgsqVW9r (@CrozrX)

#SABCS2021 MSKCC HER2, cont. Outcome analysis in met HER2+ using PFS endpoint shows worse outcome for PIK3CA pathway mutations, as well as MAPK pathway alterations. These may be acquired. Lab validation performed. MAPK and PI3K are independent of each other. ADCs still work. (@GeorgeSledge51)

#SABCS2021 MSK HER2: My take is that this nice work suggests preference for ADCs over kinase inhibitors in setting of MAPK and PI3K pathway alterations. (@GeorgeSledge51)

#SABCS2021 genomic analysis of 733 HER2 positive tumors from MSKCC. PIK3CA mutations confer resistance in prior work. PI3K alterations common, as were MAPK alterations, in NF1 and HER2. MAPK alterations more common in mets. (@GeorgeSledge51)

#SABCS2021 Tamoxifen and uterine cancer: Tam uterine cancers have fewer PIK3CA mutations. Tamoxifen can activate PI3K cross-talk which can be blocked by alpelisib in the uterus, so that tam-induced uterine CA does not need PIK3CA. Interesting biology. (@GeorgeSledge51)

It’s super important in breast cancer. PARPs for BRCA1/2,alpelisib for PIK3CA, evidence of resistance to aromatase inhibitors and or SERDs with ESR1 mutations. I’ve also done lots of off label targeting that has dramatically prolonged lives. (@Dr_RShatsky)

7) Poster: Alpelisib + endocrine therapy (ET) in patients with HR+, HER2–, PIK3CA‑mutated advanced breast cancer (ABC) previously treated with cyclin‑dependent kinase 4/6 inhibitor (CDK4/6i): Biomarker analyses from the Phase II BYLieve study @hoperugo (@prat_aleix)

6) Poster: Effect of Duration of Prior Cyclin-Dependent Kinase 4/6 Inhibitor (CDK4/6i) Therapy (≤6 mo or >6 mo) on Alpelisib Benefit in Patients HR+ HER2–, PIK3CA-Mutated Advanced Breast Cancer (ABC) From BYLieve @hoperugo @evaciruelos (@prat_aleix)

Innovative therapy for #penilecancer-challenging rare tumor with molecular heterogeneity (HER, PI3K, Notch, DNA-repair, cell-cycle alterations), generally low TMB-VEGF+PD1i promising-HPV targeting T-cells being evaluated @JadChahoud @MoffittNews @GTumors https://t.co/IDMrUmIK0R (@sonpavde)