May 31, 2020 - 08:05 pm Posted in ASCO and ASH Posted in ASCO Conference Coverage Posted in Breast Posted in Lymphoma (includes NHL, HL, CNS Lymphoma) Posted in Melanoma (includes BCC) Posted in Multiple Myeloma 0 Comments
Sunday’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting featured late-breaking data from a phase 3 trial evaluating early local therapy in metastatic breast cancer and the results of the phase 3 ENDURANCE trial.
Other important studies from the meeting were the ALPHA trial, which is evaluating an off-the-shelf chimeric antigen receptor (CAR) T-cell therapy, and the C-144-01 trial, which is evaluating an autologous tumor infiltrating lymphocyte (TIL) therapy.
Early local therapy offers no survival benefit in patients with de novo metastatic breast cancer and an intact primary tumor, according to the results of a phase 3 trial by the ECOG-ACRIN Research Group (Abstract LBA2).
The trial included 256 patients who received optimal systemic therapy before being randomly assigned to either continue optimal systemic therapy (n=131) or receive optimal systemic therapy with locoregional therapy (n=125).
The 3-year overall survival (OS) rate was not different for the locoregional therapy arm compared with the optimal systemic therapy alone arm (68.4% vs 67.9%; P=0.63) and neither was the risk of death (HR=1.09; 90% CI, 0.80 – 1.49).
Although the locoregional therapy arm had a reduced risk of locoregional recurrences/progression compared with the optimal systemic therapy alone arm (HR=0.37; 95% CI, 0.19 – 0.73), no improvements were seen for health-related quality of life (HRQOL). At one timepoint (18 months), HRQOL was significantly worse for the locoregional therapy arm (P=0.001).
“For de novo stage metastatic breast cancer, existing data supports that locoregional therapy does not improve survival and should not be routinely applied in this population,” said study discussant Julia White, MD, professor of radiation oncology at The Ohio State University.
The replacement of carfilzomib for bortezomib in a regimen of bortezomib, lenalidomide, and dexamethasone (VRd) did not improve outcomes for patients with newly diagnosed multiple myeloma, results showed in the second interim analysis of the phase 3 ENDURANCE trial (Abstract LBA3).
Patients who received carfilzomib, lenalidomide, and dexamethasone (KRd; n=545) had a similar progression-free survival (PFS; HR=1.04; 95% CI, 0.8 – 1.3; P=0.74) and OS (HR=0.98; 95% CI, 0.71 – 1.36; P=0.92) to those who received VRd (n=542). A higher proportion of particularly good partial responses was seen with KRd compared with VRd (55.5% vs 49.9%).
KRd had a significantly higher rate of cardiac, pulmonary, and renal treatment-related adverse events (16.1% vs 4.8%; P<0.001), while VRd had a significantly higher rate of peripheral neuropathy (53.4% vs 24.4%; P<0.001). No difference in frequency of secondary primary cancers was seen.
Study discussant Jesus Berdeja, MD, director of myeloma research at Sarah Cannon Research Institute, pointed out that KRd costs nearly $16,000 more per cycle than VRd, which totals to a nearly $100,000-difference for 12 cycles.
“In newly diagnosed multiple myeloma without high-risk features, VRd and KRd appear to be equivalent options for frontline treatment,” Dr Berdeja said. “Comorbidities and toxicity profiles should guide the choice between the two regimens in any individual patient.”
An off-the-self allogeneic CAR T-cell therapy known as ALLO-501 appeared safe and showed clinical activity in a small group of patients with relapsed or refractory large B-cell or follicular lymphoma, according to data from the single-arm phase 1 ALPHA trial (Abstract 8002).
“Allogeneic CAR T-cell therapy may provide the benefits of autologous CAR T-cell therapy, while also addressing its challenges,” said study presenter Sattva Neelapu, MD, MD Anderson Cancer Center. “It has the potential to treat all eligible patients, the convenience of repeat dosing, and simplifies the logistics of manufacturing.”
Patients received CD19-targeted ALLO-501 at one of three dose levels and, during lymphodepleting chemotherapy, an investigational monoclonal antibody called ALLO-647, which targets CD52. Patients were heavily pretreated (median of 4 prior therapies), and 4 patients previously received autologous CAR T-cell therapy.
About one-third of patients (7 of 22) had cytokine release syndrome, which included only one grade 3 event and no grade 4. Half of patients developed infection, most of which was grade 1 (23%) or 2 (18%). There were no reports of graft-versus-host disease.
At a median follow-up of 3.8 months, 12 of 19 patients (63%) available for efficacy analysis achieved a response, which included 7 complete responses (37%). Nine patients who achieved a response continue to have a response.
Dr. Neelapu said these results suggest that the safety and the short-term efficacy, in terms of the response rates, for this product is “comparable” to autologous CAR-T products that are currently in clinic. “Further follow-up is necessary to determine the durability of those responses.”
Autologous TIL therapy lifileucel appeared safe and to have clinical activity in patients with unresectable metastatic melanoma, according to the results of cohort 2 from the phase 2 C-144-01 trial (Abstract 10006).
Lifileucel is an autologous adoptive cell transfer therapy that involves surgically resecting a patient’s tumor and sending it to the manufacturing facility. Tumor infiltrating lymphocytes (TILs) are then obtained from the tumor, expanded, shipped back to clinical sites, and infused into the patient. Patients in cohort 2 (n=66) received lifileucel that was cryopreserved before shipment. Patients also received up to 6 doses of interleukin-2 after infusion to promote expansion of the TILs.
Most patients (97.0%) had grade 3 or 4 treatment-emergent adverse events, with thrombocytopenia (81.8%), anemia (56.1%), febrile neutropenia (54.5%), and neutropenia (39.4%) being the most common. The number of adverse events decreased over time.
Overall, 24 (36.4%) patients achieved a response, which included 2 complete and 22 partial responses. The disease control rate was 80.3%. At a median follow-up of 18.7 months, the median duration of response had not yet been reached (range, 2.2 – 26.9+ months). Responses were seen across subgroups, which include age, PD-L1 status, and BRAF mutation status.
“Notable, observed responses tended to deepen over time,” said study presenter Amod Sarnaik, MD, Moffitt Cancer Center. “These data therefore demonstrate potential efficacy and durability of response in a patient population with severely limited treatment options.”
By Christina Bennett, MS
The live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting kicked off this morning with highlights sessions that captured some of the most important studies.
The gastrointestinal cancer session featured four studies, one of which was a phase 2/3 trial that compared donafenib to sorafenib in liver cancer. HER2CLIMB and MINDACT were both discussed during the breast cancer session. Although not discussed this morning, the results of PHERGAIN dropped at this meeting and offer a de-escalation strategy for patients with early breast cancer.
Patients with unresectable or metastatic hepatocellular carcinoma who received donafenib in the first-line setting lived a median of nearly two months longer than patients who received standard of care sorafenib (12.1 months vs 10.3 months), results showed in the open-label, randomized phase 2/3 trial (Abstract 4506).
Patients in the donafenib arm (n=334) also had a 17% reduced risk of death compared with the sorafenib arm (n=334; HR=0.831; 95% CI, 0.699 – 0.988; P=0.0363). However, no difference was seen between the donafenib arm and sorafenib arm for progression-free survival (PFS; 3.7 vs 3.6 months; P=0.2824), objective response rate (4.6% vs 2.7%; P=0.2448), and disease control rate (30.8% vs 28.7%; P=0.5532).
Donafenib appeared to have a better safety profile, with a significantly lower rate of drug-related adverse events that led to treatment interruption compared with sorafenib (25.2% vs 36.1%; P=0.0025). The donafenib arm also had a significantly lower rate of drug-related adverse events of grade 3 or higher (37.5% vs 49.7%; P=0.0018).
Marcus Noel, MD, associate professor of medicine, Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, cautioned that this study was conducted in China and is not an international study.
“Not sure if this is going to be able to extrapolate across the globe, but certainly donafenib has a place in first-line therapy, further pushing sorafenib to the side,” he said.
Tucatinib in combination with trastuzumab and capecitabine extended overall survival (OS) and delayed disease progression in the central nervous system (CNS) for patients with HER2-positive metastatic breast cancer and brain metastases, results showed from an exploratory efficacy analysis of the phase 2 HER2CLIMB trial (Abstract 1005).
Trial participants were randomly assigned to receive tucatinib in combination with trastuzumab and capecitabine (n=410) or placebo in combination with trastuzumab and capecitabine (n=202). The exploratory analysis included only patients with brain metastases at baseline, of which 291 of 612 (48%) randomized to treatment had.
Patients with brain metastases in the tucatinib arm had a 68% reduced risk of disease progression in the CNS compared with the placebo arm (HR=0.32; 95% CI, 0.22 – 0.48; P<0.0001) and a nearly 6-month gain in median CNS PFS (9.9 vs 4.2 months).
Patients in the tucatinib arm also had a 42% reduced risk of death compared with the placebo arm (HR=0.58; 95% CI, 0.40 – 0.85; P=0.005), and an approximately 6-months gain in overall survival (OS; 18.1 vs 12.0 months). The intracranial response rate more than doubled with tucatinib compared with placebo (47% vs 20%; P=0.03).
“HER2CLIMB serves as a wonderful story for the liberalization of clinical trial entry criteria and inclusion of patients that we need in clinical trials and who need novel therapeutics as well,” said Erika Hamilton, MD, Sarah Cannon.
A long-term analysis of the phase 3 MINDACT trial confirmed that the 70-gene signature MammaPrint assay can identify which breast cancer patients with a high clinical-pathological risk do not need adjuvant chemotherapy (Abstract 506).
Among the intention to treat population with a median follow-up of 8.7 years, patients with high clinical risk but low genomic risk who received adjuvant chemotherapy (n=749) had a small gain in distant metastasis-free survival (DMFS) compared with patients who did not receive chemotherapy (n=748; 92.0%; 95% CI, 89.6 – 93.8% vs 89.4%; 95% CI, 86.8 – 91.5).
A subgroup analysis among hormone-receptor positive and HER2-negative patients revealed no difference in DMFS between treatment groups for patients over the age of 50, yet a 5% difference for patients 50 years or younger, favoring treatment with chemotherapy (93.6%; 95% CI, 89.3% – 96.3% vs 88.6%; 95% CI, 83.5 – 92.3%).
“MINDACT showed us that patients with clinical high, genomic low disease continue to do well without chemotherapy at 8 years of follow-up,” said Angela de Michele, MD, University of Pennsylvania. She cautioned that the DMFS gain seen with chemotherapy for premenopausal patients “may be due to a lack of ovarian function suppressant in the non-chemotherapy arm.”
A PET/CT scan with fluorodeoxyglucose (FDG) tracer helped identify which patients with HER2-positive early breast cancer were most likely to benefit from trastuzumab and pertuzumab with endocrine therapy, according to the results of the PHERGAIN trial (Abstract 503).
Patients with HER2-positive disease were randomized to receive either trastuzumab and pertuzumab with chemotherapy (n=71) or trastuzumab and pertuzumab with endocrine therapy (n=285).
A PET/CT scan was used to guide treatment for patients in the chemotherapy-free arm by having patients undergo imaging after 6 weeks of treatment. If the scan showed a response, patients continued on the chemotherapy-free regimen. If not, patients switched to trastuzumab and pertuzumab with chemotherapy. Patients in the chemotherapy-containing arm also underwent imaging but the results were not used to guide treatment.
For the chemotherapy-free arm, patients who had a PET response achieved a higher pathologic complete response rate compared with patients who did not have a PET response (37.9% vs 25.9% P=0.069).
Study presenter Javier Cortes, MD, PhD, IOB Institute of Oncology, Hospital Quirónsalud, Medica Scientia Innovation Research, and Vall d’Hebron University of Oncology, said the chemotherapy-free strategy did not “jeopardize” breast conserving surgery and was also associated with a “more favorable” toxicity profile.
By Christina Bennett, MS
Ahead of this weekend’s live broadcast of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting, late-breaking data dropped for three potentially practice-changing studies that will be presented during Sunday’s Plenary Session: JAVELIN Bladder 100, KEYNOTE-177, and ADAURA.
The addition of avelumab to best supportive care (BSC) in the maintenance setting appeared to benefit patients with unresectable advanced urothelial carcinoma who had received first-line platinum-based chemotherapy, according to an interim analysis of the phase 3 JAVELIN Bladder 100 trial (Abstract LBA1).
At median follow-up of approximately 19 months, overall survival (OS) was significantly longer for patients who received avelumab plus BSC (n=350) compared with BSC alone (n=350; HR=0.69; 95% CI, 0.56-0.86; P=0.0005). This benefit was seen across all subgroups. Patients with PD-L1–positive tumors also had significantly prolonged OS with avelumab plus BSC compared with BSC alone (HR=0.56; 95% CI, 0.40-0.79; P=0.0003).
Progression-free survival (PFS) was significantly longer for patients who received avelumab plus BSC compared with BSC alone (HR=0.62; 95% CI, 0.52-0.75; P<0.001), including those with PD-L1–positive tumors (HR=0.56; 95% CI, 0.43-0.73).
Patients who received avelumab plus BSC had a higher frequency of any grade (98.0% vs 77.7%) or grade 3 or higher (47.4% vs 25.2%) adverse events (AEs) compared with BSC alone. Common grade 3 or higher AEs for both arms were urinary tract infection, anemia, hematuria, fatigue, and back pain, all of which occurred at similar frequencies between arms.
Study presenter Thomas Powles, MD, Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, described the safety profile of avelumab as “in line” with other immune checkpoint inhibitors in this setting.
“Overall, avelumab first-line maintenance therapy in patients whose disease has not progressed with platinum-based induction chemotherapy is a new first-line standard of care for advanced urothelial cancer,” said Dr. Powles.
Pembrolizumab showed superior PFS compared with chemotherapy in patients with microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer, meeting the primary endpoint of the phase 3 KEYNOTE-177 trial (Abstract LBA4).
At median follow-up of approximately 28 months, median PFS was more than 8 months longer for the pembrolizumab arm (n=153) compared with the chemotherapy arm (n=154; 16.5 vs 8.2 months), with a 40% reduction in risk of disease progression (HR=0.60; 95% CI, 0.45-0.80; P=0.0002).
At one year, PFS was higher for the pembrolizumab arm compared with the chemotherapy arm (55.3% vs 48.3%), which remained at 2 years (37.3% vs 18.6%). The overall response rate was also higher for the pembrolizumab arm compared with the chemotherapy arm (43.8% vs 33.1%), as was the complete response rate (11.1% vs 3.9%).
Pembrolizumab appeared to have a better safety profile, eliciting a lower frequency of grade 3 or higher AEs than chemotherapy (22% vs 66%). Also, no treatment-related deaths were reported for the pembrolizumab arm, while one was reported for the chemotherapy arm.
Study presenter Thierry Andre, MD, Sorbonne University and Saint-Antoine Hospital, described the PFS improvement seen with pembrolizumab as “clinically meaningful” and said pembrolizumab should be the “new standard of care” for this patient population.
Adjuvant osimertinib showed significantly improved disease-free survival (DFS) compared with placebo for patients with EGFR-mutation–positive NSCLC in the phase 3 ADAURA trial (Abstract LBA5).
The trial included 682 patients with stage IB to IIIA EGFR-mutation–positive NSCLC who were randomized to receive adjuvant osimertinib (n=339) or placebo (n=343) after complete tumor resection. Patients were given the option of having adjuvant chemotherapy before the assigned treatment.
The trial met its primary endpoint, showing an 83% reduction in risk of disease for patients with stage II to IIIA disease who received adjuvant osimertinib compared with placebo (DFS HR=0.17; 95% CI, 0.12 – 0.23; P<0.0001). The osimertinib arm had a 2-year DFS rate of 90% and placebo 44%.
When stage IB patients were included in the analysis, the osimertinib arm had a 79% reduction in risk of disease recurrence (DFS HR=0.21; 95% CI, 0.16 – 0.28; P<0.0001), with a 2-year DFS rate of 89% for osimertinib and 53% for placebo.
Common AEs seen with osimertinib were diarrhea (46%), paronychia (25%), dry skin (23%), and pruritis (19%), all of which were higher than those receiving placebo. No reported AEs with osimertinib lead to death. Overall, 3% of patients who received osimertinib developed interstitial lung disease and 7% QTc prolongation.
“Adjuvant osimertinib is the first targeted agent in a global randomized trial to show statistically significant and clinically meaningful improvement disease-free survival in patients with stage IB to IIIA EGFR-mutation–positive non-small cell lung cancer,” said study presenter, Roy Herbst, MD, PhD, Yale School of Medicine and Yale Cancer Center.
By Christina Bennett, MS
June 02, 2019 - 09:06 pm Posted in ASCO Conference Coverage Posted in Pancreatic Posted in Policy and Value (includes Cost, Quality, Reimbursement, Guidelines, Pathways, Insurance) Posted in Prostate Posted in Sarcoma 0 Comments
Today, four plenary sessions dropped at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting featured results from three phase 3 trials: ENZAMET, ANNOUNCE, and POLO as well as encouraging data about the impact of Medicaid expansion under the Affordable Care Act (ACA).
Medicaid Expansion Closes Racial Disparities Gap (Abstract LBA1)
When the ACA was implemented in 2010, states were permitted to expand Medicaid access. A retrospective study found that states that expanded Medicaid had a reduction in racial disparities in time to cancer treatment.
Using data from electronic health records, researchers observed timely treatment (ie, treatment initiation within 30 days of diagnosis) for adult patients younger than 65 with a diagnosis of advanced or metastatic cancer. The study population included more than 30,000 patients, and depending on the Medicaid expansion status of the state in which they lived, patients were labeled as participating in Medicaid expansion or not.
When Medicaid was not expanded, a significantly lower percentage of African American patients received timely treated compared with white patients (43.5% vs 48.3%; P<0.001). When Medicaid was expanded, this racial disparity gap did not exist (49.6% vs 50.3%; P=0.63).
“The disparities disappeared under the expansion,” summed up study presenter Amy Davidoff, PhD, Yale University.
Enzalutamide for the Win in Metastatic Prostate Cancer (Abstract LBA2)
Enzalutamide outperformed standard non-steroidal anti-androgens for men with metastatic hormone-sensitive prostate cancer, according to data from an interim analysis of the randomized, phase 3 ENZAMET trial.
Patients (n=1,125) received a testosterone-suppressing medicine followed by treatment with enzalutamide or a standard of care non-steroidal anti-androgen: bicalutamide, nilutamide, or flutamide.
For the overall patient population, the 3-year overall survival (OS) rate was 79% for men treated with enzalutamide; 72% for men treated with bicalutamide, nilutamide, or flutamide. This resulted in a 33% reduced likelihood in risk of death for men treated with enzalutamide (HR=0.67; 95% CI, 0.52-0.86; P=0.002).
In particular, an OS benefit for enzalutamide was seen among men with high volume disease (HR=0.74; 95% CI, 0.55-1.01) or no planned early docetaxel (HR=0.51; 95% CI, 0.36-0.73), but not for those with planned early docetaxel (HR=0.90; 95% CI, 0.62-1.31).
“There is a delay in progression with an improvement in overall survival, but there is toxicity,” cautioned study presenter Christopher Sweeney, MBBS, a medical oncologist at the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute. “Ezalutamide actually increased the docetaxel-related toxicity.”
Olaratumab Flops in Phase 3 for Advanced Soft Tissue Sarcomas (Abstract LBA3)
Despite encouraging survival data in the previous phase 1b/2 trial, olaratumab in combination with doxorubicin failed to improve survival in patients with advanced soft tissue sarcomas in the phase 3 ANNOUNCE trial. Olaratumab in combination with doxorubicin was granted accelerated approval in 2016, but in light of the ANNOUNCE trial results, olaratumab is in the process of being withdrawn from the market.
No clear reason was offered for the failure of olaratumab in the phase 3 trial, but a few possibilities were floated, such as the control arm having a particularly high OS and not limiting study entry to treatment-naïve patients.
Offering a partial explanation for the initial survival benefit seen in the early-phase trial, study discussant Jaap Verweij, MD, PhD, Erasmus University Medical Center, said, “A critical issue in phase 2 studies, certainly in a group of diseases as heterogenous as soft tissue sarcomas, are small numbers of patients.”
Olaparib Hits its Target in BRCA-Positive Metastatic Pancreatic Cancer (Abstract LBA4)
Maintenance therapy with olaparib, a PARP inhibitor, after first-line, platinum-based chemotherapy extended progression-free survival (PFS) for patients with germline BRCA-positive metastatic pancreatic cancer, according to the results of the phase 3 POLO trial. Final OS results are still maturing.
The trial included metastatic pancreatic cancer patients with a BRCA1 or BRCA2 germline mutation who received chemotherapy for at least 16 months and then were randomly assigned maintenance therapy with either olaparib or placebo.
The median PFS was 7.4 months for the olaparib arm and 3.8 months for the placebo arm, resulting in a 47% reduced risk of progression for patients receiving olaparib (HR=0.53; 95% CI, 0.35 – 0.82; P=0.0038).
The objective response rate was 23.1% (18 of 78 patients) for the olaparib arm and 11.5% (6 of 52 patients) for the placebo arm, with two patients on olaparib achieving a complete response; both complete responses are ongoing. The median duration of response was 24.9 months for the olaparib arm and 3.7 months for the placebo arm.
“We conclude that a strategic approach of first-line, platinum-based chemotherapy followed by maintenance olaparib treatment should become a new standard of care for patients with metastatic pancreatic cancer who have a germline BRCA mutation,” said the study presenter Hedy Kindler, MD, Professor of Medicine, University of Chicago Medicine.
by Christina Bennett, MS