Rachel Narozniak

Prolonged progression-free survival (PFS) was observed with pembrolizumab (Keytruda) monotherapy in patients with selected rare sarcoma subtypes treated in the phase 2 AcSé basket study, according to a presentation during the 2020 European Society of Medical Oncology (ESMO) Virtual Congress. These data imply that the immune checkpoint inhibitor is able to improve outcomes in multiple histologies.

 general director of the Centre Léon Bérard in Lyon, France, shared results from thesarcoma cohort, which enrolled 81 patients with rare sarcomas (incidence < 0.2/100,000/year) between September 4, 2017, and May 26, 2020. The AcSé study enrolled 24 patients with chodorma, 14 with alveolar soft-part sarcoma (ASPS), 5 with desmoplastic small round cell tumors (DSRCT), 6 with smarca4-malignant rhabdoid tumor (SMBT), and 32 with other histotypes, including epithelioid sarcoma, angiosarcoma, and chondrosarcoma, among others.

At a median follow-up of 228 days, the median PFS was 7.9 months. The median overall survival was 19.7 months, with 33 deaths. The PFS advantage differed by sarcoma subtype and was “superior in patients with alveolar soft part sarcoma, chordoma, and also in patients with desmoplastic small round cell tumors” compared with other histotypes, including SMBT, Blay said (

 = .013). At the data cut-off in May 2020, the median PFS had not been reached in the chordoma and ASPS subsets. In the OS analysis, survival was also longer with chordoma and ASPS versus SMBT, DSCRT, and other subtypes (

ASPS, chordoma, DSCRT, and SMBT are not consistently associated with TLS, PD-L1 expression, high tumor mutational burden, or cell infiltrates, which could be evaluated to select patients likely to respond to immunotherapeutic approaches.1 “[These data suggest] that sarcoma can be responsive to immunotherapy using anti–PD-L1 in selected rare histological subtypes, and additional work is needed to better define the [role] of this treatment in the future for these rare subsets,” Blay said.

Confirmed objective response rate, the primary end point of the study, was partial response in 12 patients, translating to a PR rate of 15%. At 84 days and at the data cut-off date, March 17, 2020, there were no complete responses, but the disease control rate increased from 48% to 52% and the progressive disease rate decreased from 35% to 32%. Treatment benefit was most pronounced in patients with ASPS, SMBT, and epithelioid sarcoma, where 35.7% (5 of 14), 33.3% (2 of 6), and 20% (1 of 5) achieved a PR, respectively.

Patients received 200 mg of pembrolizumab every 21 days until progression, unacceptable toxicity, or patient or physician decision to halt therapy, for a maximum of 2 years. The median number of treatment cycles was 6 (interquartile range, 4-11). A total of 76% of patients prematurely discontinued pembrolizumab after a median of 4 cycles. Thirty-three patients died after a median of 3 cycles; 27 deaths were to cancer.

There were 88 toxicities recorded in 28 patients, 13 and 51 of which were related to pembrolizumab and disease progression, respectively. Six of the former toxicities were grade 3 in nature and included 1 cognitive disorder, 1 case of bullous pemphigoids, 1 instance of febrile aplasia, and 1 report of erysiplas. There was also 1 grade 4 case of lipasemia, which represented the sole grade 4 treatment related toxicity. Of the 7 grade 3 or 4 serious adverse events (AEs), 4 resulted in treatment withdrawals and 2, treatment interruption. AEs attributed to disease progression entailed 26, 5, and 1, grade 3, 4, and 5 events, respectively.

The nonrandomized, parallel arm, open-label AcSé trial (NCT03012620), launched by the French National Cancer Institute and sponsored by the French network of comprehensive cancer centers (Unicancer), is testing the safety and efficacy of pembrolizumab in patients with metastatic or refractory rare tumor types.1 Specifically, the study is enrolling patients with unresectable locally advanced or metastatic disease that is resistant or refractory to standard therapy or for which no standard therapy exists or is contraindicated, and for which no other experimental treatment options are available.

 Patients must not have received a diagnosis for any other malignancy within the past 5 years to be eligible to participate.

AcSé will enroll a maximum of 350 patients 15 years or older who have not received prior treatment with anti–PD1 or anti–PD-L1 across 7 cohorts: sarcoma, ovarian cancer, primary central nervous system lymphomas, thyroid cancer, malignant neuroendocrine cancer, germ-cell cancer, and natural killer/T-cell lymphoma.

 Each cohort, excluding the sarcoma group, will accrue 20 to 50 patients. The 2-stage Bayseian enrichment trial design has a different objective for each stage. In the first stage, investigators will identify any “possibly sensitive indications” of efficacy; in the second, they will compare outcomes among subsets of patients in the identified cohorts to distinguish between subpopulations of patients who may benefit from pembrolizumab and patients for whom there is no evidence of efficacy. Use of pembrolizumab in this investigational context is supported by a nationwide exploratory program that has allowed access to anti–PD-L1 therapies outside of their existing indications.

Data from the sarcoma cohort of the phase 2 AcSé basket study presented during the 

 showed that pembrolizumab (Keytruda) monotherapy prolonged progression-free survival (PFS) in selected rare sarcoma subtypes, supporting the immune checkpoint inhibitor’s (ICI’s) ability to improve outcomes across histotypes.1

Jean-Yves Blay, MD, Phd, general director of the Centre Léon Bérard in Lyon, France, shared results from thesarcoma cohort, which enrolled 81 patients with rare sarcomas (incidence < 0.2/100,000/year) between September 4, 2017, and May 26, 2020. The AcSé study enrolled 24 patients with chodorma, 14 with alveolar soft-part sarcoma (ASPS), 5 with desmoplastic small round cell tumors (DSRCT), 6 with smarca4-malignant rhabdoid tumor (SMBT), and 32 with other histotypes, including epithelioid sarcoma, angiosarcoma, and chondrosarcoma, among others.1

The rationale for evaluating pembrolizumab in the AcSé basket study is based on limited but observed activity with ICIs in unselected sarcoma populations, whether as single agents or combined with PD-1– or CTLA4–directed drugs. When co-administered with antiangiogenic agents, immunotherapy prolonged PFS in selected subtypes, including ASPS, Blay said. Immunologic monotherapy has also demonstrated anti-cancer capacities in rare subtypes such as chordoma and rhabdoid tumors.

Elucidating predictive biomarkers will help refine the role of immunotherapy in the treatment of sarcoma, but identifying these indicators is challenging because there are more than 150 “different types or molecular subtypes of disease,” Blay explained.1 However, a paper published by Helmink et al in 

 in January 2020 specified B cells and tertiary lymphoid structures (TLS) as potential indicators of response to immune checkpoint blockade, providing a direction for biomarker-focused research in this space.

“Additional translational research is foreseen to understand the determinants of response in these sarcoma histotypes,” Blay concluded.

1. Blay JV, Ray-Coquard I, Penel N, et al. High clinical benefit rates of single agent pembrolizumab in selected rare sarcoma histotypes: first results of the AcSé pembrolizumab study. Presented at: 2020 European Society for Medical Oncology Virtual Congress; September 19-21, 2020. Abstract 1619O.

2. Secured access to pembrolizumab for patients with selected rare cancer types. (AcSé). ClinicalTrials.gov. Updated November 1, 2019. Accessed September 21, 2020. 

https://clinicaltrials.gov/ct2/show/NCT03012620

3. Helmink BA, Reddy SM, Gao J, et al. B cells and tertiary lymphoid structures promote immunotherapy response. 

. 2020;577(7791):549-555. doi:10.1038/s41586-019-1922-8

Articles

Prolonged progression-free survival was observed with pembrolizumab monotherapy in patients with selected rare sarcoma subtypes treated in the phase 2 AcSé basket study, according to a presentation during the 2020 European Society of Medical Oncology Virtual Congress. 

Pembrolizumab Extends Progression-Free Survival in Rare Sarcoma Subtypes

-mutant, hormone receptor–positive, HER2-negative advanced breast cancer in the SOLAR-1 trial experienced prolonged overall survival (OS) with alpelisib (Piqray) and fulvestrant even though the study did not cross the prespecified O’Brien-Fleming efficacy boundary (

 ≤ .0161), according to research presented at the 2020 ESMO Virtual Congress.

The median OS was prolonged by 7.9 months versus fulvestrant alone (HR, 0.86; 95% CI, 0.64-1.15; 

 = .15) and the data additionally suggested a survival benefit in various patient subgroups with no new safety signals.

Results from the concluding OS assessment of the phase 3 trial (NCT02437318), presented by Fabrice André, MD, PhD, lead author of the SOLAR-1 study, showed that at a median follow-up of 30.8 months, the median OS was 39.3 months (95% CI, 34.1-44.9) with alpelisib and fulvestrant and 31.4 months (95% CI, 26.8-41.3) with fulvestrant. In total, 169 and 172 patients were randomized to the alpelisib and fulvestrant arms, respectively, each of whom had not received prior chemotherapy and experienced disease progression on or after treatment with an aromatase inhibitor.

-mutant cohort was a key secondary end point [for which] statistical testing was planned to be conducted if the primary progression-free survival [PFS] analysis was positive,” said André, director of research at Gustave Roussy Cancer Center in Villejuif, France.

Positive PFS data from the SOLAR-1 study, published in 2019, which led not only to the subsequent OS analysis, but also to the May 24, 2019, approval of alpelisib in combination with fulvestrant for postmenopausal women and men with hormone receptor–positive, HER2-negative, 

-mutant advanced or metastatic breast cancer as detected by an FDA approved test following progression on or after an endocrine-based regimen.

Investigators used a 3-look group sequential design to support the OS evaluation, which was based on 181 deaths at the April 23, 2020, cut-off date. At that time, 12.4% of patients receiving alpelisib (n = 169) remained on treatment versus 4.1% of fulvestrant-treated patients (n = 172).

In addition to the nearly 8-month increase in median OS seen in the PIK3CA-mutant cohort, André and fellow researchers also saw survival improvements with the doublet therapy in patients with lung and/or liver metastases and individuals with mutated 

in circulating tumor DNA (ctDNA). The median OS in this subpopulation was prolonged by 14.4 months with alpelisib and fulvestrant (n = 84) versus fulvestrant alone (n = 86). Specifically, the median OS was 37.2 months (95% CI, 28.7-43.6) with the combination and 22.8 months (95% CI, 19.0-26.8) with the chemotherapy (HR, 0.68; 95% CI, 0.46-1.00).

 in ctDNA, the median OS continued to favor alpelisib and fulvestrant. The median OS was 34.4 months 95% CI, 28.7-44.9 in 92 patients and 25.2 months (95% CI, 20.7-29.6) in 94 patients, respectively (HR, 0.74; 95% CI, 0.51-1.08).1 “The median overall survival was approximately 9 months longer for the alpelisib arm. Data suggest that patients with a 

 mutation detected by ctDNA may have greater disease burden or more aggressive disease that might respond better to alpelisib,” André said.

Beyond the superior median OS seen in the 

-mutant cohort and 2 patient subgroups, investigators also witnessed an improvement in the median time to chemotherapy (mTTC) with the dual-drug regimen (HR, 0.72; 95% CI, 0.54-0.95) in a post-hoc exploratory analysis of the 

-mutant cohort. Treatment with the alpelisib-fulvestrant combination led to a mTTC of 23.3 months (95% CI, 15.2-28.4) compared with 14.8 months (95% CI, 10.5-22.6) in the placebo arm. “The median time to chemotherapy was about 8.5 months longer for the alpelisib arm, suggesting that alpelisib alone delayed time to first chemotherapy,” André noted.

PFS2 was also evaluated as an exploratory end point in the 

-mutant cohort and was measured from the time of randomization to the first documented instance of disease progression on the first new systemic antineoplastic therapy initiated after discontinuation of study treatment or death from any cause. The median PFS2 was 22.8 months (95% CI, 18.5-26.3) with alpelisib and 18.2 months (95% CI, 12.8-22.2) with fulvestrant (HR, 0.80; 95% CI, 0.62-1.03).

At a median follow-up of 42.4 months, “adverse events [AEs] were consistent with those in prior reports and no new safety signals were observed,” André said. Notably, the incidence of hyperglycemia “did not increase with longer time on treatment,” he added.

The 3 most common grade 3 AEs in the alpelisib arm were hyperglycemia (33.1%), diarrhea (7.0%), and decreased weight (5.3%). No grade 4 AEs were seen aside from grade 4 hyperglycemia, which affected 11 of the 284 patients included in the alpelisib safety analysis.

Grade 3 AEs also occurred at a low frequency in the fulvestrant arm. The most prevalent grade 3 events were fatigue (1.0%), hyperglycemia (0.7%), and diarrhea (0.7%). The only grade 4 AE was hyperglycemia, which affected just 1 of the 287 patients evaluated for safety.1

One AE of special interest, rash, was observed in 153 (53.9%) and 27 (9.4%) of patients who received alpelisib-fulvestrant versus fulvestrant, respectively. The majority of these events were grade 1 or 2, André said.

The phase 3 SOLAR-1 (NCT02437318) study enrolled 572 patients with hormone receptor-positive, HER2-negative advanced breast cancer who received prior endocrine therapy. Patients were enrolled into 2 cohorts based on 

 mutation status (mutated vs non-mutated) and randomly assigned in a 1:1 ratio to receive 300 mg of alpelisib plus 500 mg of fulvestrant or fulvestrant alone. In each cohort, randomization was stratified by the presence or absence of lung or liver metastases and prior receipt of a CDK4/6 inhibitor. Of the 572 patients enrolled, 341 had confirmed tumor-tissue 

 mutations. The primary end point was progression-free survival in the 

-mutant cohort. Secondary end points included overall response and safety.

The statistically significant prolongation of PFS initially observed in the SOLAR-1 study is now supported by a numeric increase in OS. Previously announced PFS data from SOLAR-1 showed that alpelisib and fulvestrant nearly doubled PFS in the 

-mutant cohort compared with fulvestrant alone. At a median follow-up of 20 months, the PFS was 11.0 months (95% CI, 7.5-14.5) with the doublet therapy and 5.7 months (95% CI, 3.7-7.4) with fulvestrant (HR, 0.65; 95% CI, 0.50-0.85; 

 < .001). At 12 months, PFS, the primary end point of the study, remained superior in the combination arm (46.3% vs 32.9%).

Although not statistically significant, the increase in OS seen in alpelisib-treated patients is clinically relevant, and when coupled with the statistically significant and clinically relevant PFS data, the improvements in OS and mTTC “further support” the use of alpelisib and fulvestrant in this poor prognostic population, the authors concluded.

1. André F, Ciruelos EM, Juric D, et al. Overall survival (os) results from SOLAR-1, a phase III study of alpelisib (ALP) + fulvestrant (FUL) for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020. LBA18.

2. FDA approves alpelisib for metastatic breast cancer. News release. FDA. Updated May 28, 2019. Accessed September 17, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-alpelisib-metastatic-breast-cancer​

3. André F, Ciruelos E, Rubovszky G, et al; SOLAR-1 Study Group. Alpelisib for 

-mutated, hormone-receptor positive advanced breast cancer. 

. 2019;380(20):1929-1940. doi:10.1056/NEJMoa1813904

Postmenopausal patients with PIK3CA-mutant, hormone receptor–positive, HER2-negative advanced breast cancer in the SOLAR-1 trial experienced prolonged overall survival with alpelisib and fulvestrant even though the study did not cross the prespecified O’Brien-Fleming efficacy boundary (P ≤ .0161), according to research presented at the 2020 ESMO Virtual Congress.

Alpelisib and Fulvestrant Show Benefit for Breast Cancer Subgroups in SOLAR-1

The combination of atezolizumab (Tecentriq), carboplatin, and nab-paclitaxel (Abraxane) increased pathological complete response (pCR) by 10% or more in “immune-rich” patients with high-risk and locally advanced triple-negative breast cancer (TNBC), as well as turned PD-L1 negative tumors positive most patients treated with immunotherapy, according to the phase 3 NeoTRIPaPDL1 trial data presented at the 2020 ESMO Virtual Congress.

“PD-L1 expression was significantly associated with pCR, which increased with higher PD-L1 expression on immune cells,” said Giampaolo Bianchini, an author of the NeoTRIPaPDL1 study (NCT02620280) who presented the findings.

The pCR with atezolizumab was highest in the study’s “immune-rich” groups, defined as patients with PD-L1–positive immune cells (PDL1 IC+), or stromal tumor-infiltrating lymphocyte (sTILs) or intermediate/high intratumoral TILs (iTILs).1 Data showed that the pCR with the atezolizumab-containing regimen was 86.9% versus 72.0% with chemotherapy alone in patients with IC2/3 (PD-L1 expression of ≥ 5%; Δ + 14.96%) and 56.2% versus 44.0% in patients with IC1 (PD-L1 ≥ 1% and < 5%; Δ + 12.25%). A pCR benefit was not seen in patients with PD-L1 expression of less than 1% (IC0), where chemotherapy alone led to a higher pCR than the immune checkpoint inhibitor (ICI)-based combination (41.07% vs 35.09%) with a Delta that favored chemotherapy by 5.9%. The P value for this test for interaction, which measured log PD-L1 IC to correct skewness, was .02.

The overall pCR rates between treatment arms were 52.3% with atezolizumab and 47.7% with chemotherapy (

The NeoTRIPaPDL1 trial tested the addition of atezolizumab to nab-paclitaxel in 280 women with high-risk (T1cN1; T2N1; and T3N0) and locally advanced TNBC versus carboplatin and nab-paclitaxel alone. After completing 8 cycles of either regimen, all patients in this intention-to-treat population underwent definite surgery. Investigators collected samples from all 260 patients evaluable for pCR response in the per-protocol population at baseline to assess sTILs, iTILs, and PD-L1 expression on ICs and tumor cells (TCs), and their dynamics and association with pCR. The objective of the analysis was to validate the presence of 40% or more sTILs following 1 cycle of treatment on day 1 of cycle 2 (d1c2), as predictive of pCR. Notably, d1c2 served as an early surrogate of pCR.

PD-L1 expression on ICs and TCs was measured using Roche’s VENTANA PD-L1 (SP142) Assay. Baseline patient samples amassed from the 260 patients evaluable for pCR indicated that PD-L1 IC was balanced across all 3 expression groups. The percentages of patients with IC0, IC1, and IC2/3 in the atezolizumab and chemotherapy-only arms, respectively, were 44.53% versus 42.75%; 37.50% versus 38.17%, and 17.97% versus 19.08%.

 = .005) were disproportionately higher in the arm that received carboplatin and nab-paclitaxel. This “significant imbalance” in sTILs and iTILs could be responsible for the smaller differences in pCR seen between arms, said Bianchini, head of the Breast Cancer Group in the department of Medical Oncology and head of the translational and immunotherapy research group at the IRCCS Ospedale San Raffaele in Milan, Italy.

Samples collected on d1c2 additionally demonstrated that in both treatment arms, sTILs observed on d1c2 were more informative than baseline sTILs and ΔTILs and were predictive of pCR. “The majority of patients demonstrated a robust increase of TILs after 1 cycle, which was similar among arms, suggesting that [this increase] is mostly driven by chemotherapy,” Bianchini said.

At d1c2, 33.7% of patients met or exceeded 40% sTILs in the general population. In the atezolizumab group, patients who had a 40% or higher percentage of sTILs (n = 21) had a pCR of 71.4% compared with 28.0% who did not meet this threshold (n = 56). The odds ratio (OR) was 6.83 (95% CI, 2.24-20.87; 

Among patients receiving chemotherapy alone, a 40% or greater percentage of sTILs translated to a pCR of 63.16% in the 38 patients who met or surpassed this sTIL threshold and a pCR of 33.9% in the 59 patients who did not (OR, 3.34; 95% CI, 1.43-7.83; 

Rates of tumor absence measured on d1c2 may also be predicative of pCR. “Following the biopsy on day 1, cycle 2, tumor cells were not found in almost 1 out of 3 samples in the atezolizumab arm, which was double the observed rate in the chemotherapy arm,” said Bianchini. Specifically, no tumor cells were observed in 32.6% of patients treated with atezolizumab versus 15.65% of patients treated with chemotherapy.

At d1c2 evaluation, 37 patients in the atezolizumab group had no tumor cells and 77 patients. had observed tumor cells. The resulting in a pCR rates were 78.3% and 38.9%, respectively (

 = .0002). Eighteen patients in the chemotherapy arm showed no signs of a tumor whereas 97 did. The pCR rate was consequently higher in patients with absent tumor (77.7% vs 45.3%; 

PD-L1 dynamics from baseline to d1c2 were “strong and divergent by arm of therapy.” A key finding of this analysis was that atezolizumab turned most PD-L1–negative tumors positive. “Notably, 2 out of 3 PD-L1–negative tumors converted to [PD-L1–]positive tumors in the atezolizumab arm,” Bianchi said. In total, PD-L1 IC+ rose from 45.4% (IC1, 32.0% and IC2/3, 13.3%, respectively) to 74.6% (IC1, 9.3% and IHC2/3, 65.3%, respectively). At baseline, 54.7% of patients in the atezolizumab arm were IC0, compared with 25.3% at d1c2. “PD-L1 expression in immune cells strongly increased, suggesting that this is a factor activation driven by atezolizumab,” he added.

An overall decrease in PD-L1 positivity was observed in the chemotherapy-only arm, where PD-L1 IC+ fell from 52.1% (IC1, 38.4% and IC2/3, 13.7%, respectively) at baseline to 37.9% (IC1, 23.2% and IC2/3, 14.7%, respectively). At enrollment, 47.4% of patients were PD-L1–negative. This number increased to 62.1% at d1c2.

In early-stage TNBC, administering an ICI in combination with standard neoadjuvant chemotherapy is hypothesized to improve efficacy by decreasing tumor associated macrophages and increasing TILs. TNBC is an aggressive form of breast cancer associated with poor outcomes, due largely to the paucity

of effective targeted therapies. Immunotherapy-based combinations have been recognized for their ability to significantly increase pCR in TNBC, where checkpoint inhibitor-driven spikes in TILs are associated with elevated pCR.

Although data from Bianchini et al’s analysis of TILs, PD-L1 expression, and the dynamics of their intersection in the NeoTRIPaPDL1 per-protocol population provide insight on the interaction of immunotherapy and chemotherapy in this high-risk setting, monoclonal antibody use in this space remains opaque. This is in part due to discordance in results from various neoadjuvant studies in TNBC, with conflicting results seen in NeoTRIPaPDL1, the phase 3 KEYNOTE-522 (NCT03036488) and IMpassion031 trials (NCT03197935), and the phase 2 GeparNUEVO study (NCT02685059).

To date, KEYNOTE-522 is the largest trial to evaluate immunotherapy-containing neoadjuvant chemotherapy in TNBC. Findings from the evaluation demonstrated a “significantly higher” pCR rate among patients receiving pembrolizumab (Keytruda) with pre-operative chemotherapy versus chemotherapy alone.

 This trend was also apparent in the IMpassion031 study, where atezolizumab and chemotherapy outperformed chemotherapy alone in patients with early TNBC. A statistically significant, clinically meaningful improvement in pCR was seen with the multi-class regimen, causing IMpassion031 to meet its primary end point.

Conversely, in the GeparNUEVO study, patients with metastatic TNBC who were treated with neoadjuvant durvalumab (Imfinzi) and nab-paclitaxel achieved a higher, but not statistically significant pCR compared with patients who only received nab-paclitaxel.

 Hope S. Rugo, MD, FASCO, called the findings from these 4 investigations “perplexing” and posited that this observed discordance signifies that the field of TNBC must continue its efforts to “understand which patients benefit from immunotherapy” in her invited discussant session.

1. Bianchini G. Tumour infiltrating lymphocytes (TILs), PD-L1 expression and their dynamics in the NeoTRIPaPDL1 trial. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020. LBA13.

2. Lee JS, Yost SE, Yuan Y. Neoadjuvant treatment for triple negative breast cancer: recent progresses and challenges. 

. 2020;12(6):1404. doi:10.3390/cancers12061404

3. Schmid P, Cortes J, Pusztai L, et al; KEYNOTE-522 Investigators. Pembrolizumab for early triple-negative breast cancer. 

. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549

4. Roche’s Tecentriq in combination with chemotherapy (including Abraxane) meets primary endpoint of improved pathological complete response, regardless of PD-L1 status, as initial treatment for people with early triple-negative breast cancer. News release. Roche. June 18, 2020. Accessed September 19, 2020. https://www.roche.com/media/releases/med-cor-2020-06-18.htm

5. Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. 

 2019;30(8):1279-1288. doi:10.1093/annonc/mdz158

6. Rugo HS. Predicting benefit from neoadjuvant therapy. Discussion presented at: 2020 European Society for Clinical Oncology Virtual Congress.; September 18-21, 2020; virtual. Presentation ID 4898.

The combination of atezolizumab, carboplatin, and nab-paclitaxel increased pathological complete response by 10% or more in “immune-rich” patients with high-risk and locally advanced triple-negative breast cancer, as well as turned PD-L1 negative tumors positive most patients treated with immunotherapy, according to the phase 3 NeoTRIPaPDL1 trial data presented at the 2020 ESMO Virtual Congress.

NeoTRIPaPDL1 Trial Showed TIL Activity With Guidance From PD-L1 Status

After passage of the Affordable Care Act (ACA), women with ovarian cancer who were pre-medicare-aged were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis compared to prior to the ACA, according to findings presented at the 2019 ASCO Annual Meeting.

Findings demonstrated a relative gain of 1.7% in early-stage (defined as stage I or II) diagnosis of ovarian cancer in women aged 21 to 64, compared with women &ge;65, many of whom were presumed to be on Medicare. The 1.7% increase indicates that of the 22,000 women diagnosed annually, approximately 400 more have the potential to be diagnosed at a stage that is both early and treatable, thereby extending potential survival time, lead author Anna Jo Smith, MD, MPH, said.

The study also demonstrated an increase of 1.6% in women aged 21 to 64 treated within 30 days of diagnosis, compared with the control group.

Among publicly insured women aged 21 to 64, there were relative gains of 2.5% in both the diagnosis of ovarian cancer and time to treatment.

Smith, a resident in the Johns Hopkins Department of Gynecology and Obstetrics, at Baltimore, Maryland, and Amanda Nickles Fader, MD, director of the Kelly Gynecologic Oncology Service and an associate professor at Johns Hopkins, evaluated ovarian cancer data from the National Cancer Database, which records data on approximately 70% of all new ovarian cancer cases. They concluded that the ACA led to an increase in ovarian cancer treatment and more treatment occurring within 30 days of diagnosis, thereby increasing chances of survival for women with ovarian cancer.

&ldquo;Detecting and treating ovarian cancer at an early stage saves lives and lowers healthcare costs compared with treatment of cancer at a more advanced, incurable stage,&rdquo; said Smith. &ldquo;Having health insurance plays a major role in whether or not a woman has access to care providers who can monitor symptoms and act on those symptoms if necessary.&rdquo;

The study authors were able to measure the improvement in ovarian cancer and treatment by using a difference-in-differences approach, which allows analysis using a comparator control group that is unaffected by the changes being evaluated. In this case, the investigators compared younger women with those &ge;65 years of age, who would likely be on Medicare and uninfluenced by the passage of ACA.

In the United States, 22,000 women receive a diagnosis of ovarian cancer each year. More than 75% of those with early-stage ovarian cancer live 5 years or more; that percentage falls to less than 30% for those diagnosed at an advanced stage. As there is no screening test to detect ovarian cancer at an early stage, the cancer can often be present but undetected for years, due in part to the cancer&rsquo;s tendency to present subtle symptoms. The coverage that the ACA afforded to an expanded number of Americans enabled women with the cancer to not only visit their doctors, but also report symptoms to their physicians, complete laboratory tests to confirm the presence of cancer, and subsequently receive treatment. The expanded coverage accessible through the ACA rendered early detection of the cancer increasingly possible.

By 2017, nearly 12.7 million individuals gained health coverage following the ACA&rsquo;s 2010 implementation. Meanwhile, the proportion of uninsured Americans decreased from 16% in 2010 to less than 12% by 2016.

The investigators used data on stage at ovarian cancer diagnosis and time to treatment for women aged 21 to 64 and &ge;65 who were diagnosed from 2004 to 2009 (pre-ACA; 35,842 patients) and 2011 to 2014 (post ACA; 37,145 patients).

Investigators examined the type of insurance women had and adjusted findings for race, rural demographics, neighborhood household income, education level, distance traveled for care, Census region, and practice setting for care. They also adjusted based on the Charlson comorbidity score, which predicts risk of death within 1 year of hospitalization for people with comorbid conditions.

The study was funded by a Johns Hopkins Department of Gynecology and Obstetrics Kelly Society Grant, and the investigators will expand their purview to include the years beyond 2014, to assess the impact of the ACA on early-stage diagnosis and treatment for women with gynecologic cancers.

Smith AJ, Nickles Fader A. Impact of the Affordable Care Act on early-stage diagnosis and treatment for women with ovarian cancer.

After passage of the Affordable Care Act, women with ovarian cancer who were pre-medicare-aged were more likely to be diagnosed at an early stage and receive treatment within 30 days of diagnosis compared to prior to the ACA, according to findings presented at the 2019 ASCO Annual Meeting.

Rachel Narozniak | Authors

Articles

Pembrolizumab Extends Progression-Free Survival in Rare Sarcoma Subtypes

Alpelisib and Fulvestrant Show Benefit for Breast Cancer Subgroups in SOLAR-1

NeoTRIPaPDL1 Trial Showed TIL Activity With Guidance From PD-L1 Status

Ovarian Cancer Diagnosis, Time to Treatment Improved Since ACA