The OBR Blog

By Mary Ellen Schneider

This year’s annual meeting of the American Society of Hematology (ASH) featured new research on chimeric antigen receptor (CAR) T-cell therapy and bispecific T-cell engager (BiTE) molecules, along with trends toward treating cancer patients with immunotherapies earlier in the course of their disease.

The meeting, which was held virtually for the first time, also highlighted studies evaluating the extent and impact of racial and ethnic health disparities in hematology and oncology.

Health Disparities Highlighted

“As part of caring for patients and our citizens, ASH chose to have a significant light shine upon disparities in health care, or differences in outcomes between different groups of our patients,” Chancellor Donald, MD, an assistant professor of clinical medicine at Tulane University in New Orleans, told OBR.

Bringing attention to disparities in outcomes and access offers the potential for “immediate improvement in outcomes for those persons without a new diagnostic test, or without a new drug,” Dr. Donald said.

The ASH plenary session put the spotlight on poor treatment outcomes for Black patients younger than 60 years with acute myeloid leukemia (AML). In a study that looked both at Surveillance Epidemiology End Results (SEER) data and molecular features by race, researchers found that younger Black patients had a 27% higher likelihood of death than white patients. They also discovered that Black patients had a lower frequency of prognostically favorable NPM1 mutations (Abstract 6).

Another study that focused on health disparities identified a greater risk for cancer-associated thrombosis among Black patients, compared with their white counterparts. These disparities were especially prominent when the researchers looked only at pulmonary embolism (Abstract 203).

What is driving the disparities in cancer-associated thrombosis? The researchers acknowledged possible contributions from underlying biological traits. But they also pointed to the contribution of systemic racism, access to care, and the severity of underlying comorbidities.

“Since current risk prediction models for cancer-associated thrombosis do not include race and ethnicity as parameters, future studies should examine if incorporating these factors can improve predictive value,” said Alisa S. Wolberg, of the University of North Carolina at Chapel Hill and one of the ASH scientific program co-chairs. Dr. Wolberg highlighted the study as part her “Best of ASH” presentation.

Other health disparities research presented at this year’s ASH included a study exploring the impact of living in a socioeconomically disadvantaged neighborhood for Black and Hispanic people with AML. Researchers found that this “structural violence” led to worse survival for minority patients in the study (Abstract 217).

Latest Data in CAR T-Cell Therapy, BiTEs  

The ASH annual meeting also included a variety of studies on CAR T-cell therapy, from clinical trials to real-world data.

“What strikes me now is that in the CD19 CAR T-cell space, you’re getting much more robust real-world data,” Catherine Bollard, MD, director of the Center for Cancer and Immunology Research at Children’s National Hospital in Washington, D.C., and a professor of pediatrics and immunology at George Washington University, told OBR.

Among the noteworthy research, Dr. Bollard pointed to a real-world study that investigated the tumor-specific factors driving inherent or acquired resistance to CAR T cells in large B-cell lymphoma (Abstract 556). The study, led by researchers at Stanford University, identified CD58 status as an important biomarker for durable response to CAR T cells in large B-cell lymphoma.

This type of real-world data will be even more important as CAR T-cell therapy moves earlier in the treatment of disease, Dr. Bollard said.

“As we continue to expand the reach of new targeted therapies, it is imperative that we deeply study our patients to determine the mechanisms that underscore success, and perhaps even more importantly, failure,” said Leslie S. Kean, MD, PhD, of Boston Children’s Hospital and Dana-Farber Cancer Institute and one of the ASH scientific program co-chairs. She highlighted Abstract 556 as part of her “Best of ASH” presentation.

Dr. Kean also highlighted findings from the primary analysis of the phase 2, Zuma-5 trial, which evaluated axicabtagene ciloleucel (axi-cel) in patients with follicular and marginal zone lymphoma (Abstract 700), noting that one of themes of the ASH meeting was an expansion of cellular therapies beyond their initial indications.

“The maturation of the field is evidenced by multiple commercial CARs now being investigated in these more indolent lymphoma patients,” Dr. Kean said.

Dr. Kean also pointed to an early study looking at the combination of the CAR T product lisocabtagene maraleucel (liso-cel) with the BTK inhibitor ibrutinib for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL). In the phase 1 TRANSCEND CLL 004 study, researchers found promising efficacy and a manageable safety profile with the combination (Abstract 544).

Other immunotherapy studies presented at ASH were focused on the use of these treatments earlier in the course of therapy.

Dr. Kean pointed to a phase 3 trial in children with high-risk first relapse B-cell precursor acute lymphoblastic leukemia (ALL) that assessed the BiTE molecule blinatumomab, compared with high-risk consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. Blinatumomab monotherapy achieved significantly better event-free survival, causing the trial’s data monitoring committee to recommend early termination of enrollment due to benefit (Abstract 268).

Another study focused on treatment with a BiTE molecule earlier in the course of therapy was a phase 2 study that examined the use of a hyper-CVAD chemotherapy regimen with sequential blinatumomab in adults with newly diagnosed Philadelphia chromosome-negative B-cell ALL (Abstract 464). The researchers found that the combination was effective in front-line treatment, with a high complete response rate and high percentage of patients achieving measurable residual disease negativity.

Potential New Treatments in Multiple Myeloma

Dr. Kean also highlighted two clinical studies of antibody-based and CAR T-cell therapies for the treatment of multiple myeloma.

The phase 1b/2 CARTITUDE-1 study looked at ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-directed CAR T-cell therapy, in the treatment of relapsed/refractory multiple myeloma (Abstract 177). Researchers reported an encouraging progression-free survival profile of at least a year. The safety and efficacy data indicate that larger studies of this agent are warranted, Dr. Kean said.

Along with CAR T-cell advances, Dr. Kean pointed to a new antibody-based therapy with potential in relapsed/refractory multiple myeloma. A phase 1, first-in-human study, evaluated talquetamab, a first-in-class bispecific antibody that binds to the G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) and CD3 (Abstract 290). Researchers reported a manageable safety profile for the antibody treatment.

“This study suggests that there continue to be ‘new kids on the block’ for these otherwise difficult-to-treat patients,” Dr. Kean said.

December 11, 2020 - 08:12 pm Posted in Breast Posted in SABCS Conference Coverage comments0 Comments

by Chase Doyle

Day 4 of the 2020 San Antonio Breast Cancer Symposium (SABCS) virtual meeting featured advances in early treatment monitoring, a surprising setback for HDAC inhibition in endocrine-resistant disease, and better selection of patients for neoadjuvant chemotherapy in high-risk early breast cancer (EBC).

Circulating Tumor Cells Predict Overall Survival in Metastatic Breast Cancer

A simple blood test may be enough to predict survival in metastatic breast cancer less than one month after initiating treatment.

Results of a large, pooled analysis confirm that at a median of 29 days after treatment initiation, follow-up circulating tumor cell (CTC) assessments strongly predicted overall survival (OS) in patients with metastatic breast cancer (Abstract GS4-08).

Patients with evidence of CTC response had a significantly increased OS of 32.2 months compared with 17.9 months in patients without a treatment response (hazard ratio [HR] = 0.49).

Furthermore, early treatment monitoring of CTCs, which are shed from the primary tumor into the bloodstream, was predictive of survival in all tumor subtypes.

“With the increasing number of treatment options available to patients with metastatic breast cancer, being able to predict and monitor treatment responses rapidly will be critical to aiding treatment decisions,” said lead study author, Wolfgang Janni, Professor and Director of the Women’s Clinic at Ulm University Hospital, in Germany. “These data indicate that CTC dynamics can predict the trajectory of the disease a little more than four weeks after initiating treatment.”

For this study, the researchers analyzed global pooled datasets from peer-reviewed and published studies of 4,079 patients with metastatic breast cancer who had undergone baseline and follow-up CTC measurements using the CellSearch test.

According to Dr. Janni, “This provides an advantage over conventional imaging methods and can help physicians determine very early on whether a treatment should be continued,” said Dr. Janni. “It is also very reassuring that CTC dynamics predicted outcomes for all breast cancer subtypes.”

As precision medicine approaches continue to evolve, CTC dynamics combined with circulating tumor DNA may also be used to guide initial treatment decisions, concluded Dr. Janni.

Entinostat Disappoints in Endocrine-Resistant Breast Cancer

Despite recent treatment advances, resistance to endocrine therapy remains a significant clinical problem in breast cancer. Results of a randomized Phase 3 trial suggest that histone deacetylase (HDAC) inhibition is unlikely to be the solution (Abstract GS4-02).

Data from the E2112 study, which randomized 608 patients with hormone-receptor positive (HR+), HER2-negative advanced breast cancer to endocrine therapy plus entinostat, an HDAC inhibitor, versus endocrine therapy alone, showed no improvement in survival with the combination of exemestane and entinostat versus control.

“We were very disappointed in these results after so many years of work, but we’ve realized again the importance of confirmation of promising data,” said lead study author, Roisin M. Connolly, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

The findings showed no significant difference in progression-free survival (PFS) with the addition of entinostat to endocrine therapy, and the overall response rate was low in both study arms (4.6% in the entinostat arm and 4.3% in the placebo arm).

With a median OS of 23.4 months in the intervention arm and 21.7 months in the placebo arm, no significant difference in OS was observed.

Subgroup analysis for both progression-free survival (PFS) and OS showed similar results in all subgroups, including prior CDK inhibitor exposure, said Dr. Connolly, who noted that these results differ from those of the multicenter ACE trial where a modest PFS advantage was observed with the addition of an HDAC inhibitor, chidamide or tucidinostat, to exemestane to a Chinese patient population.

“Although robust preclinical and clinical data supported the development of E2112, our results highlight the importance of Phase 3 confirmation of promising Phase 2 data,” said Dr. Connolly. “The short median PFS of approximately 3 months and low overall response rate observed with an endocrine-therapy backbone suggest that improved decision-making tools are required to help determine who may need chemotherapy versus alternative strategies in this setting.”

When asked to speculate on the future of HDAC inhibitors, Dr. Connolly noted several ongoing investigations of HDAC inhibitors in various combinations. After the results of this study, however, HDAC inhibitors “clearly do not have a role in this patient population,” she observed.

“HDAC inhibitors have been combined with chemotherapies and other targeted therapies over the years but have unfortunately not broken into the solid tumor space,” concluded Dr. Connolly. “Ongoing work will be required to see where they may fit in the future.”

Neoadjuvant Nab-Paclitaxel Improves pCR vs Dose-Dense Paclitaxel

Data from a large Phase 3 trial could help select patients for neoadjuvant chemotherapy in high-risk HR+, HER2-negative breast cancer.

Results from the neoadjuvant part of the ADAPT HR+/HER2– trial showed that patients randomized to nab-paclitaxel had improved rates of pathological complete response (pCR) compared with those receiving standard paclitaxel (Abstract GS4-03).

“Use of neoadjuvant nab-paclitaxel appears to be highly effective and well tolerated and was associated with a significantly higher pCR,” said lead study author, Sherko Kuemmel, MD, Director of the Breast Centre of the Essen-Mitte Clinics, in Germany. “We will have to wait for the final analysis of this huge trial to see if there’s a benefit in disease-free survival and overall survival, but these results are very promising.”

Dr. Kuemmel noted that dose-dense chemotherapy is currently the standard of care in high-risk EBC. In some trials of HR+, HER2-negative EBC, however, neoadjuvant nab-paclitaxel has been shown to superior to solvent-based paclitaxel with respect to pCR and survival.

For the neoadjuvant part of this study, a total of 864 high-risk patients were randomized between 8x weekly nab-paclitaxel and a dose-dense regimen of paclitaxel. Results of the primary endpoint showed a pCR of 20.8% in the nab-paclitaxel arm compared with 12.9% in patients receiving paclitaxel (P=.002).

ADAPT is also the first large prospective study confirming recurrence score (RS) >25 as a predictive factor for pCR in patients treated with neoadjuvant chemotherapy, said Dr. Kuemmel, who noted that RS >25 and tumor size (<cT2) were shown to be independent predictive factors for pCR.

Ki67 as an additional dynamic marker further separates the high-risk group and identifies patients who may not benefit from intensive chemotherapy,  reported Dr. Kuemmel.

Optimal therapy for these patients is being investigated in the ongoing ADAPTcYcle trial, which is evaluating a standard endocrine approach together with CDK4/6 inhibition versus chemotherapy in patients who are not candidates for chemotherapy alone in the adjuvant treatment setting.

When asked whether the improvement in pCR would translate into disease-free or OS benefit, Dr. Kuemmel noted results from the recent GeparSept trial.

“The difference in pCR in this subgroup of endocrine-positive disease translated to improved overall survival, so we will have to wait a few months to see just how many patients benefit with nab-paclitaxel instead of paclitaxel,” he concluded.

December 10, 2020 - 09:12 pm Posted in Breast Posted in SABCS Conference Coverage comments0 Comments

by Chase Doyle

Day 3 of the 2020 San Antonio Breast Cancer Symposium (SABCS) virtual meeting featured advances in how to optimally use adjuvant chemotherapy for early-stage breast cancer (EBC), a setback in the metastatic setting of triple-negative breast cancer (TNBC), and mixed news for survivors looking to conceive post-treatment.

No Adjuvant Chemo Needed for Postmenopausal Women with EBC and Low Recurrence Score

Many women with the most common form of breast cancer can safely avoid chemotherapy and still achieve similar outcomes with endocrine therapy alone, according to an interim analysis of the SWOG S1007 RxPONDER trial (Abstract GS3-00).

Findings from the study, which evaluated the role of chemotherapy in more than 5,000 women with hormone receptor (HR)-positive, HER2-negative breast cancer with 1 to 3 positive nodes and a recurrence score (RS) ≤25, suggest that postmenopausal women can forgo adjuvant chemotherapy without compromising invasive disease-free survival (iDFS).

“This will save tens of thousands of women the time, expense and potentially harmful side effects that can be associated with chemotherapy infusions,” said lead study author Kevin Kalinsky, MD, director of the Glenn Family Breast Center at Winship Cancer Institute of Emory University, Atlanta.

At 54% of the anticipated iDFS events in the overall population, the analysis showed that postmenopausal women with an RS score ≤25 did not benefit from adjuvant chemotherapy in any subgroup.

Conversely, investigators observed a five-year iDFS improvement with the addition of chemotherapy followed by endocrine therapy in all premenopausal subsets. Although the follow-up is still limited, investigators also identified a 5-year survival benefit of 1.3% favoring chemotherapy followed by endocrine therapy versus endocrine therapy alone in premenopausal women with positive nodes and an RS score ≤25.

Although the results of the study are clear, the explanation for the findings may be less so, according to Kent Osborne, MD, Dudley and Tina Sharp Chair for Cancer Research, Baylor College of Medicine, in Houston.

“The results clearly show no benefit to adding chemotherapy to standard endocrine therapy in post-menopausal patients, despite having positive nodes,” said Dr. Osborne. “This emphasizes that node positivity, while an important prognostic marker, is not a predictive marker of chemotherapy sensitivity. In premenopausal patients, a different result was obtained.”

Dr. Osborne explained the majority of premenopausal patients in this study received tamoxifen as endocrine therapy. The standard approach today, however, would be ovarian suppression plus either tamoxifen or an aromatase inhibitor, which would have been superior to tamoxifen alone in this subgroup.

“Since adjuvant chemotherapy causes ovarian suppression in many premenopausal patients, the patients in this study actually received ovarian suppression plus tamoxifen, while tamoxifen alone was the endocrine therapy for the no-chemotherapy arm,” he concluded. “We may never know whether the difference in outcome in this subset is due to the endocrine effects of chemotherapy.”

Ipatasertib Shows No PFS Benefit in Advanced TNBC

Findings of a Phase 3 study could cast doubt on the future of AKT and PI3K inhibition in triple-negative breast cancer (TNBC).

The addition of AKT inhibitor ipatasertib to paclitaxel in patients who harbored PIK3CA, AKT1, or PTEN alterations did not significantly improve progression-free survival (PFS) in the first-line setting of advanced TNBC, according to primary results from IPATunity130 Cohort A (Abstract GS3-04).

With a median follow-up of 8.3 months, data from the double-blind, placebo-controlled, randomized Phase 3 trial showed a PFS of 6.1 months in patients receiving paclitaxel alone versus 7.4 months with ipatasertib. However, the stratified PFS hazard ratio of 1 was not statistically significant, said Rebecca Dent, MD, associated professor at the National Cancer Center Singapore, in Singapore.

Confirmed overall response showed a slight improvement from 35% with paclitaxel compared to 39% with the addition of ipatasertib, and similar rates of clinical benefit.

Safety was consistent with previously reported results for this combination, which showed higher rates of diarrhea in the ipatasertib combination arm.

Dr. Dent highlighted the surprising differences in results between this Phase 3 study and the randomized Phase 2 LOTUS trial of ipatasertib, which showed “impressive improvement in overall survival and a modest improvement in PFS.”

“The question on everybody’s mind is, ‘Why after such amazing data from both randomized Phase 2 trials with AKT inhibition in advanced TNBC have we gotten these [negative] results?’” said Dr. Dent. “I think it’s important to recognize that TNBC is very heterogeneous. It’s really just an overarching term to describe a breast cancer that has several different pathways that are upregulated.”

As for the future of AKT or PI3K inhibitors in TNBC, Dr. Dent noted that translational work exploring potential biomarkers of benefit from ipatasertib is ongoing as researchers continue to learn about this disease.

“I don’t think the story is over yet,” said Dr. Dent. “I think it’s only just beginning.”

Meta-Analysis Finds Significantly Reduced Odds of Pregnancy after Breast Cancer  

New research highlights the significant impact of breast cancer and its treatment on subsequent chance of pregnancy.

Results of the systematic review and meta-analysis of 39 studies that identified women who had been pregnant after a breast cancer diagnosis and included data on 114,573 breast cancer patients showed a 60% lower chance of getting pregnant post-treatment in breast cancer survivors compared with the general population (Abstract GS3-09). In fact, only survivors of cervical cancer had lower odds of subsequent pregnancy.

“While results of this meta-analysis provide reassuring evidence on the feasibility and safety of conceiving in women with prior history of breast cancer, the reduced chances of future conception among breast cancer survivors should raise awareness about the importance of offering complete oncofertility counseling,” said Lead study author, Eva Blondeaux, MD, a medical fellow in oncology at IRCCS Policlinico San Martino Hospital.

Dr. Blondeaux and colleagues also identified higher risk of delivery and fetal complications, particularly in women exposed to prior chemotherapy. Compared with women in the general population, breast cancer survivors had 50% higher risk of having a baby with low birth weight, 16% higher risk of having a baby that was small for gestational age, a 45% higher risk of preterm labor, and a 14% higher risk of having a caesarean section.

Importantly, however, the researchers found no significant increased risk of congenital abnormalities or other delivery complications. Although there is a need for closer monitoring of these pregnancies, said Dr. Blondeaux, the lack of negative effects on survival indicate that many women can successfully go through pregnancy after breast cancer.

“Returning to a normal life after cancer should be considered a crucial ambition in cancer care in the 21st century,” said Dr. Blondeaux. “This study shows the need for deeper consideration of patients’ pregnancy desire as a crucial component of their survivorship care plan and wish to return to a normal life.”

December 09, 2020 - 09:12 pm Posted in Breast Posted in SABCS Conference Coverage comments0 Comments

by Chase Doyle

Cyclin-dependent kinase (CDK) inhibitors have improved survival of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer, but which subsets of patients benefit most from these agents, and when to administer them, remain unanswered questions.

Day 2 of the 2020 San Antonio Breast Cancer Symposium (SABCS) virtual meeting featured important updates to the landmark CDK inhibitor trials in both the early-stage and metastatic settings of HR-positive (HR+) breast cancer as well as follow-up analysis of the antibody-drug conjugate, trastuzumab deruxtecan (T-DXd), which continues to demonstrate unprecedented durations of response against HER2-positive disease.

Abemaciclib Could Change Practice in Early Breast Cancer

Updated results of the monarchE study provided encouraging results to oncologists who have already begun to prescribe adjuvant abemaciclib for patients with very high-risk early breast cancer (EBC).

MonarchE is a global, randomized, Phase 3 trial that is evaluating the combination of the CDK4/6 inhibitor abemaciclib and standard endocrine therapy (ET) among 5,637 randomly assigned patients with HR+, HER2−, node-positive EBC at high risk of early recurrence.

Priya Rastogi, MD, associate professor at the University of Pittsburgh School of Medicine and medical director of the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, presented extended follow-up data, which continued to show a reduction in the risk of developing invasive disease-free survival (iDFS) and distant relapse-free survival (DRFS) in combination with standard endocrine therapy (Abstract GS1-01). Abemaciclib in combination with endocrine therapy is the first CDK4/6 inhibitor to demonstrate efficacy and tolerability for patients with HR+, HER2-negative, node-positive, high-risk early breast cancer.

With 395 events and an additional 3.6 months of median follow-up (now at approximately 19 months), the combination of abemaciclib and endocrine therapy also resulted in statistically significant improvement in iDFS in patients whose tumors are a high Ki-67 level, an indicator of cell proliferation.

Safety was consistent with the second interim analysis and the known safety profile of abemaciclib, said Dr. Rastogi, who noted that most discontinuations due to adverse events occurred within the first five months of study treatment and that patients who required a dose hold or discontinuation were able to remain on study treatment.

During Tuesday’s press conference, C. Kent Osborne, MD, of Baylor College of Medicine, in Houston, called the results “very encouraging,” especially in the subgroup of tumors with high proliferation.

Nevertheless, Dr. Osborne urged caution in the interpretation, given the relatively short follow-up and the fact that ER-positive disease often recurs years later.  Dr. Osborne also noted that this class of inhibitors is largely cytostatic rather than cytocidal, and “it remains to be seen whether the iDFS curves will come together when the drug is stopped,” he said.

“With these caveats in mind, this is still an extremely important trial that could be practice-changing in this very high-risk patient population if the results continue to be positive and show improved overall survival with longer follow-up,” Dr. Osborne concluded.

The study is ongoing until the final assessment of overall survival.

Ribocliclib: Biomarker Analysis Shows Benefit Across Main Intrinsic Subtypes of Metastatic Breast Cancer

Findings presented at the SABCS could also lead to better understanding of which patients benefit from CDK4/6 inhibition. Biomarker analysis of the Phase 3 MONALEESA trials has confirmed the independent prognostic value of intrinsic subtypes in patients with HR+, HER2-negative metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitor (abstract GS1-04).

“This study clearly shows that HER2-enriched, luminal A, and luminal B subtypes exhibited a consistent PFS benefit with ribociclib treatment, while patients with the basal-like subtype did not,” said lead study author, Aleix Prat, MD, PhD, Associate Professor at the University of Barcelona, in Spain.

Importantly, said Dr. Prat, the HER2-enriched subtype, which represents 13% of all breast cancer patients and had a very poor prognosis in the placebo arm, exhibited the greatest relative reduction in risk of progression or death with ribociclin plus endocrine therapy.

Although this is an exploratory and retrospective analysis, further validation studies will be required to firmly establish the clinical utility of intrinsic subtyping in this particular context, according to Dr. Prat.

Trilaciclib Plus Gemcitabine/Carboplatin Improves Overall Survival in Metastatic Triple-Negative Breast Cancer

Another CDK inhibitor associated with improved survival, trilaciclib is a first-in-class myelosuppression agent.

A previously reported primary analysis of a Phase 2 study of patients with metastatic triple-negative breast cancer showed, somewhat surprisingly, that administering trilaciclib prior to gemcitabine plus carboplatin significantly increased overall survival compared with gemcitabine plus carboplatin alone.

During the SABCS virtual symposium, Joyce A. O’Shaughnessy, MD, chair of Breast Cancer Research and chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center of Texas Oncology, reported final anti-tumor efficacy results for the whole study population (n=102) as well as for subgroups, according to CDK4/6 dependence and immune subtyping (Abstract PD1-06).

“Patients receiving trilaciclib prior to gemcitabine and carboplatin had higher response rates, longer PFS, and significantly improved overall survival, compared with those receiving gemcitabine and carboplatin alone,” said Dr. O’Shaughnessy, “The addition of trilaciclib significantly increased overall survival from 12.6 months to 19.8 months, with a hazard ratio of 0.37.”

Subgroup analyses also showed that anti-tumor efficacy outcomes were similar in patients with tumors categorized as CDK4/6-dependent, confirming that trilaciclib did not antagonize the anti-tumor effects of gemcitabine and carboplatin in the CDK4/6-dependent population. Furthermore, adding trilaciclib prior to gemcitabine and carboplatin appears to preserve and enhance immune system function, said Dr. O’Shaughnessy.

“These data support further investigation of the association between enhanced anti-tumor immunity and improved survival in patients with triple-negative breast cancer receiving trilaciclib prior to chemotherapy,” she concluded.

Trastuzumab Deruxtecan: Unprecedented Duration of Response in HER2-Positive Metastatic Breast Cancer

Updated results from DESTINY-Breast01, a Phase 2 study of trastuzumab deruxtecan (T-DXd) in 184 patients with HER2-positive metastatic breast cancer who had received at least two lines of anti-HER2 based therapies, continues to demonstrate clinically meaningful and durable efficacy (Abstract PD3-06).

Lead study author, Shanu Modi, MD, of Memorial Sloan Kettering Cancer Center, New York, called the updated median duration of response of 20.8 months “striking and unprecedented.”

With 20.5 months median duration of follow-up, the median PFS has also increased to 19.4 months, and the estimated percent of patients alive at 12 and 18 months is 85% and 74%, respectively. The preliminary median overall survival of 24.6 months is estimated at 35% maturity, so additional follow-up is required, said Dr. Modi.

Although the overall safety profile of T-DXd continues to demonstrate general tolerability with few treatment discontinuations, the antibody-drug conjugate is associated with the risk of lung toxicity called interstitial lung disease (ILD). Three new cases of T-DXd-related ILD were reported, including one death.

Most of the ILD events occurred during the first 12 months of treatment, suggesting that the risk is not related to a cumulative dose of T-DXd, said Dr. Modi. Continued attention to pulmonary symptoms and monitoring is warranted.

“The consistent benefit/risk profile provides confidence in treatment efficacy, which will be further evaluated in the ongoing, randomized controlled Phase 3 DESTINY-Breast02 trial of T-DXd versus investigators choice of treatment,” concluded Dr. Modi.

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