Conference Coverage

This category covers the hematology oncology conferences hosted by Binaytara Foundation.

INAVO120 trial


By Dr. Arya Mariam Roy
of Roswell Park Comprehensive Cancer Center


Development of endocrine resistance remains a challenge in the management of HR-positive HER2-negative breast cancer (HR+ HER2- BC). Alterations in PI3K signaling are one of the major factors of endocrine resistance, with mutations in PIK3CA occurring in approximately 40% of HR+ HER2- BC cases (1) . The prevention of endocrine resistance is possible through combination triplet therapy, including endocrine therapy, CDK 4/6 inhibitors, and PIK3CA inhibitors. Inavolisib, a highly potent and selective PI3Kα inhibitor, facilitates specific degradation of mutated PI3Kα, demonstrating anti-tumor activity alone and in combination with endocrine therapy and Palbociclib in preclinical models (NCT03006172) (2) . The INAVO120 trial, a phase III study, investigated the efficacy and safety of the combination of inavolisib with palbociclib and fulvestrant in metastatic PIK3CA mutant HR+ HER2- BC (NCT04191499). Dr. Komal Jhaveri presented the trial at the San Antonio Breast Cancer Conference (Jhaveri et al. Phase III study of inavolisib or placebo in combination with palbociclib and fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer: INAVO120 primary analysis. SABCS 2023)


Patients with PIK3CA-mutated HR+ HER2- metastatic or advanced breast cancer experiencing progression during or within 12 months of completing adjuvant endocrine therapy were enrolled in the trial. Key eligibility criteria included fasting glucose < 126 mg/dL and HbA1c <6.0%. The trial randomized patients 1:1 to receive inavolisib + Palbociclib + fulvestrant (intervention arm) or placebo + Palbociclib + fulvestrant (control arm) (Total N= 325). Patients were followed up until progression or toxicity. The median progression-free survival (PFS) was significantly higher in the intervention arm compared to placebo (15 vs 7.3 months, HR = 0.43, 95% CI = 0.32 – 0.59, p<0.0001). The 18-month PFS was also higher in the inavolisib combination arm (46.2% vs 21.1%). PFS improvement was observed with the triplet therapy in both primary (11.4 vs 3.7 months, HR = 0.39, 95% CI = 0.24 – 0.61) and secondary (18.2 vs 9.7 months, HR = 0.55, 95% CI = 0.38 – 0.80) endocrine resistance. Overall survival (OS) data are not mature, but interim analysis shows an improved survival trend in the triplet arm (median OS: NR vs 31.1, HR = 0.64, 95% CI = 0.43 – 0.97, p= 0.0338). Median follow-up was 21.3 months. The objective response rate (ORR) was higher in the inavolisib combination arm (ORR = 58.4% vs 25%). Stomatitis (51.2% vs 26.5%), hyperglycemia (58.6% vs 8.6%), diarrhea (48.1% vs 16%), rash (25.3% vs 17.3%) were common in the inavolisib combination arm. Grade 3-4 hyperglycemia was observed in 5.6% of patients in the inavolisib arm, and 6.2% discontinued inavolisib treatment in the combination arm due to adverse events.


The combination of inavolisib with palbociclib and fulvestrant demonstrated a significant improvement in progression-free survival (PFS) with a manageable safety profile in patients with PIK3CA-mutant HR+ HER2-advanced breast cancer who experienced recurrence on or within 12 months of adjuvant endocrine therapy. This triplet combination may represent a new standard of care for this patient population. The enrolled study population primarily consisted of Asian patients, with minimal enrollment of African Americans, limiting the analysis of the drug combination in diverse racial and ethnic groups. The trial also had a higher percentage of patients who had received adjuvant tamoxifen, and this subgroup appeared to derive greater benefit from the triplet therapy. Although the drug was well-tolerated in the study population, it is worth noting that the population was carefully selected for a lower risk of hyperglycemia, which may not fully represent the real-world population. There is a need for increased inclusion of minorities, as well as pre-diabetic and type-II diabetic patients in future studies of this drug combinations.



1. Guerrero-Zotano A, Mayer IA, Arteaga CL. PI3K/AKT/mTOR: role in breast cancer
progression, drug resistance, and treatment. Cancer Metastasis Rev. 2016;35(4):515-24.
2. Fuso P, Muratore M, D'Angelo T, Paris I, Carbognin L, Tiberi G, et al. PI3K Inhibitors in
Advanced Breast Cancer: The Past, The Present, New Challenges and Future Perspectives.
Cancers (Basel). 2022;14(9).

Updates from clinical trials from two HR+ breast cancers with neoadjuvant immune checkpoint inhibition


By Dr. Shipra Gandhi
of Roswell Park Comprehensive Cancer Center


Data from two phase III trials showed that adding immune checkpoint inhibition in the neoadjuvant setting in HR positive breast cancer was associated with increases in pCR rates. This was presented at ESMO congress 2023. Updated biomarker subgroup analyses were presented at San Antonio Breast Cancer Symposium 2023.


CheckMate 7FL (CM 7FL; NCT04109066) is a prospective, phase 3, randomized, multicenter, double-blind trial investigating nivolumab in combination with neoadjuvant chemotherapy and adjuvant endocrine therapy in patients with high-risk, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) primary breast cancer (BC). pCR (ypT0/Tis ypN0) rates with neoadjuvant nivolumab plus chemotherapy were significantly improved compared with control (24.5% versus 13.8%; odds ratio [OR] 2.05; 95% CI 1.29–3.27; p=0.0021).


KEYNOTE-756 (NCT03725059) is a global phase 3 study of neoadjuvant pembrolizumab or placebo + chemotherapy followed by adjuvant pembrolizumab or placebo + endocrine therapy in patients with early-stage high-risk ER + /HER2 –  breast cancer. KEYNOTE-756 showed a significantly increased rate of pCR with pembrolizumab plus chemotherapy versus placebo plus chemotherapy (24.3% versus 15.6%; treatment difference 8.5%, 95% confidence interval [CI] 4.2–12.8; p=0.00005).


Updated analysis from SABCS 23 showed that most of the benefit from neoadjuvant checkpoint inhibition was limited to tumors with aggressive biology, like, node positive disease, higher PD-L1 and lower ER expression.


Checkmate 7FL: Benefit of adding nivolumab to neoadjuvant chemotherapy for ER+ BC is mostly evident in patients with PDL1-high tumors, TILS> 5% and ER <=50%.


KEYNOTE-756: Larger pembrolizumab benefit in node+, higher PD-L1 and lower ER <10%.


Is this data practice-changing at this time? NO


Some questions remaining:
1. We need to await event free survival data before putting these results into practice.
2. Are there certain subgroups that derive maximum benefit from neoadjuvant checkpoint inhibition?
3. Should we send PD-L1 upfront in these patients?
4. Given increased hepatotoxicity with combining checkpoint inhibitors with CDK4/6 inhibitors, how will this fit into current treatment paradigm in the adjuvant setting?


Some comments from experts from Twitter:


Naoto T Ueno, MD, PhD: “KEYNOTE-756 confirms once again the benefit drives from less than ER 10%. I suggest that we call less than ER 10% as TNBC.”


George W Sledge, MD: “With both neoadjuvant Nivo and Pembro in ER pos BC pCR rates increase strongly as PD-L1 increases. Two questions: should we use PD-L1 as a predictive biomarker, and should we use either of these drugs in the absence of solid EFS improvements?”


Qamar Khan, MD: “EFS data absolutely needed! Also, ER 1-10 belong in TNBC trials not here. 1-10 % group is making results look better than they are.”


Dr. Sarah Sammons: “Low PR and presence of any TILs also helps us identify patients that may benefit.”


Jason A. Mouabbi, MD: “IMO until we have the EFS data, the KN-756 will not change our practice”


Jason A. Mouabbi, MD: “CheckMate 7FL: Addition of IO improved pCR in G3 PgR negative even if ER > 10% PgR negative tumors have been shown to have a poorer prognosis compared to PgR positive with some studies showing that its prognosis is similar to that of TNBC IMO: G3 ER+ PgR- should be treated like TNBC with chemoimmunotherapy.”


1. Cardoso F, O’Shaughnessy J et al. Phase 3 study of neoadjuvant pembrolizumab or placebo plus chemotherapy, followed by adjuvant pembrolizumab or placebo plus endocrine therapy for early-stage high-risk ER+/HER2− breast cancer: KEYNOTE-756. SABCS 2023
2. Loi S et al. Biomarker Results in High-risk Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Primary Breast Cancer Following Neoadjuvant Chemotherapy ± Nivolumab: an Exploratory Analysis of CheckMate 7FL. SABCS 2023.

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