Brielle Benyon

The addition of tiragolumab to atezolizumab (Tecentriq) plus carboplatin and etoposide (CE) did not result in improved survival outcomes when compared with atezolizumab plus CE in patients with untreated extensive-stage small cell lung cancer (ES-SCLC), according to findings from the randomized phase 3 SKYSCRAPER-02 clinical trial.

“The vast majority of patients with extensive-stage small cell lung cancer continue to suffer disease progression, with a median of about 5.5 months from the time of diagnosis. So there’s clearly a major unmet need for the treatment of these patients,” study author Charles M. Rudin, MD, PhD, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center, said while presenting the findings at the 2022 American Society of Clinical Oncology Annual Meeting.

The trial comprised 490 patients who were randomized to receive tiragolumab, atezolizumab and CE (n = 243) or placebo plus atezolizumab and CE (n = 247). Co-primary endpoints were overall survival (OS) and investigator-assessed progression-free survival (PFS) in a primary analysis set that actually excluded those patients with brain metastases at baseline.

Secondary endpoints were PFS and OS in the overall analysis set, including those with brain metastases.

“Brain metastases were present in about 19% of the patients on both arms at diagnosis, and about two-thirds of these were untreated at the time they started on systemic therapy,” Rudin said.

Results from a February 2022 cutoff (median 14.3-month follow-up) of the trial showed that at a median follow-up of 13.9 months, median progression-free survival (PFS) was 5.4 months in the tiragolumab-containing regimen, compared with 5.6 months in the atezolizumab plus CE group (

= .3504) in the patients enrolled in the study without the history of or had brain metastases at baseline.

For all patients in the study, median PFS was 5.1 months and 5.4 months in the tiragolumab-containing and non-containing arms, respectively.

In the cohort without brain metastases, median OS was the same (13.6 months) in both the tiragolumab and non- tiragolumab arms. In the full study population, the median OS was 13.1 months for patients given tiragolumab plus atezolizumab plus CE, compared to 12.9 months in the placebo plus atezolizumab and CE arm.

“I think I can summarize these [findings] by saying there doesn’t appear to be any subgroup that selectively benefits from the addition of tiragolumab,” Rudin said. “All of the confidence intervals overlap.”

Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 52.3% of patients in the tiragolumab arm and 55.7% in the placebo arm. Grade 3 TRAEs occurred in 0.4% of the tiragolumab arm and 2.0% in the placebo arm.

Five percent of patients treated with the tiragolumab-containing arm had TRAEs that led to treatment discontinuation, compared with 5.3% in the placebo arm.

“We saw what we expected to see in terms of toxicity of the chemotherapy backbone and atezolizumab, [and there’s] really not much difference in terms of safety signals between the 2 arms,” Rudin said.

Ultimately, the lack of benefit seen with the addition of tiragolumab on the SKYSCRAPER-02 trial mimic results previously seen on the EMPOWER-3 trial, according to Rudin.

“From a clinical standpoint, based on these data, our conclusion is that targeting TIGIT in extensive-stage small-cell lung cancer does not appear to be therapeutically relevant,” Rudin said. “We’re continuing to follow these folks and biomarker analyses will be forthcoming. I think those will be interesting in informing us about the subgroups that benefits from immunotherapy.”

Rudin CM, Liu SV, Lu S, et. al. SKYSCRAPER-02: Primary results of a phase III, randomized, double-blind, placebocontrolled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC).

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Adding tiragolumab to atezolizumab plus carboplatin and etoposide did not meet its mark of improving survival in patients with extensive-stage small-cell lung cancer. 

Tiragolumab and Atezolizumab Plus Chemotherapy Does Not Improve Survival in Small-Cell Lung Cancer

The combination of lenvatinib (Lenvima) and pembrolizumab (Keytruda) demonstrated a 50% reduction in risk of progression or death on second-line therapy vs sunitinib (Sutent) for patients with advanced renal cell carcinoma (RCC), according to findings from the phase 3 CLEAR trial (NCT02811861) presented at the 2022 American Society of Clinical Oncology Annual Meeting.

Researchers analyzed progression-free survival on next-line therapy (PFS2) in patients (n = 355) who received lenvatinib plus pembrolizumab, and compared it to patients prescribed sunitinib (n = 357) in the randomized, open-label CLEAR trial. Median PFS2 was not reached for the lenvatinib plus pembrolizumab cohort (95% CI, not evaluable), and was 28.7 months in the sunitinib cohort (95% CI, 23.0 months-not evaluable).

At the 24-month mark, PFS2 rate was 72.7% (95% CI, 67.3-77.4) and 54.2% (95% CI, 48.4-59.6) in the dual therapy and sunitinib arms, respectively. At 36 months, PFS2 rate was 61.9% (95% CI, 53.7-69.0) and 42.9% (95% CI, 32.8-52.5) in the lenvatinib/pembrolizumab arm and sunitinib arm, respectively.

“These findings remained consistent after accounting for subsequent therapies, as evidenced by PFS2 and adjusted OS,” the researchers wrote.

A total of 117 patients in the lenvatinib plus pembrolizumab cohort and 206 patients in the sunitinib cohort went on to receive another therapy. Median time to next-line therapy was 12.2 months (range, 1.45-37.36) and 6.4 months (range 0.39-28.52) in thelenvatinib/pembrolizumab and sunitinib groups, respectively.

The most common next-line of therapy was anti-VEGF treatment, mainly cabozantinib (Cabometyx) (33.0% of patients in the lenvatinib/pembrolizumab cohort and 57.7% in the sunitinib group), followed by checkpoint inhibition (30.4% and 33.6%, respectively), MTOR inhibition (8.2% and 43.1%), CTLA-4 inhibition (1.7% and 5%), and other (1.7% and 5%).

PFS2 was also seen with lenvatinib plus pembrolizumab over sunitinib in patients with favorable (not reached vs 24.7 months, 95% CI, 28.7-not evaluable), intermediate (not reached vs 23.6 months 95% CI, 19.9-NE), and poor (not reached vs 10.2 months, 95% CI, 6.6-NE) MSKCC risk groups.

Similarly, in the IMDC risk groups, median PFS2 was not reached for the favorable, intermediate, or poor-risk groups for those on lenvatinib plus pembrolizumab, though it was 34.7 months (95% CI, 28.7-NE), 23.0 months (95% CI, 17.7-NE), and 10.2 months (95% CI, 4.2-12.2), in the sunitinib groups, respectively.

Median duration of first subsequent treatment was 5.2 months for the lenvatinib plus pembrolizumab cohort (range, 0.10-31.23) and 6.8 months in the sunitinib cohort (range, 0.03-30.72).

To be eligible for the trial, patients had to have a histologically or cytologically confirmed diagnosis of RCC with clear-cell components and documented evidence of advanced disease. Patients could not have undergone prior systemic therapy have one or more measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and a Karnofsky performance score of 70 or higher.

“These results further support the use of lenvatinib plus pembrolizumab as a standard-of-care first-line treatments for patients with [advanced] RCC,” the authors wrote.

Voss MH, Powels T, McGregor BA, et al. Impact of subsequent therapies in patients (pts) with advanced renal cell carcinoma (aRCC) receiving lenvatinib plus pembrolizumab (LEN + PEMBRO) or sunitinib (SUN) in the CLEAR study. 

. 2022; 40 (suppl_16): 4514. doi: 10.1200/JCO.2022.40.16_suppl.4514

Decreased risk of disease progression or death on second-line therapy with the combination of lenvatinib and pembrolizumab vs sunitinib in the CLEAR clinical trial. 

Promise Shown With Lenvatinib Plus Pembrolizumab as SOC in Front-line Advanced RCC 

In the phase 2 GRIFFIN clinical trial (NCT02874742), adding daratumumab (Darzalex) to induction/consolidation lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone (RVd) — a combination commonly referred to as RVd — achieved durable minimal residual disease (MRD)-negativity in patients with transplant-eligible newly diagnosed multiple myeloma, according to findings presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Daratumumab is approved across lines of therapy for the treatment of multiple myeloma, and a primary analysis of the phase 2 GRIFFIN study (adding daratumumab to) RVd significantly improved the stringent complete remission rates compared with RVd, and responses deepened with longer follow-up,” said study author Cesar Rodriguez, MD, of the Mount Sinai School of Medicine.

Participants in the trial were randomized 1:1 to receive 4 daratumumab-RVd or RVd induction cycles, autologous stem cell transplant, 2 consolidation cycles of daratumumab-RVd or RVd and then 2 years of maintenance therapy with lenalidomide with or without daratumumab.

Study results from a median follow-up of 38.6 months showed that 48.1% of patients in the daratumumab plus RVd arm had a durable MRD negativity status (defined as 10-5) lasting 6 or more months, compared to 14.6% in the RVd arm. MRD negativity that lasted 12 or more months was experienced in 44.2% and 12.6% of the daratumumab plus RVd and RVd arms, respectively.

The daratumumab-containing regimen induced better MRD negativity rates for patients with high cytogenic risk, too, with 25% at the daratumumab-containing arm and 14.3% in the RVd arm lasting 6 or more months, and 18.8% and 14.3% lasting 12 or more months, respectively. For revised high cytogenic risk, MRD lasting at least 6 months was 35.7 months and 18.9 months in the daratumumab-containing arm and RVd arm, respectively, and 33.3% and 16.2% lasted 12 or more months.

“Data show that all subgroups had higher rates of MRD negativity lasting 12 months or longer at the 10-5 threshold for daratumumab/RVd versus RVd,” Rodriguez said. “At the 10-6 threshold, MRD negativity rates lasting 5 months or longer were higher for the daratumumab-RVd in most subgroups, except for the revised high cytogenetic risk group, including the 1q gain.”

Additionally, progression-free survival (PFS) was consistently better in the daratumumab/RVd cohort compared to the RVd cohort in patients who achieved MRD negativity at the 10-5 threshold. Median PFS by durable MRD negativity at 10-5 was not reached in any group.

Patients in both groups tended to have improved PFS when they had lasting MRD negativity, compared to those who did not reach MRD negativity, which, according to the authors, emphasizes the importance of MRD negativity as a surrogate endpoint.

Among those who sustained MRD negativity, only 1 patient treated with daratumumab plus RVd experienced subsequent disease progression, and 1 patient receiving RVd died of an unknown cause. Both patients had high cytogenetic risk at baseline.

“These data are consistent with previous reports that daratumumab-based therapies for newly diagnosed myeloma patients are associated with higher rates of durable MRD negativity, which translated to improved PFS,” Rodriguez concluded. “These results suggest that daratumumab-RVd therapy in transplant-eligible patients with newly diagnosed myeloma may benefit high-risk subgroups, although larger studies are needed to confirm, especially incorporating patients with revised high-risk cytogenetics, including 1q gain.”

Rodriguez C, Kaufman JL, Laubach J, et. al. Daratumumab (DARA) + lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible newly diagnosed multiple myeloma (NDMM): A post hoc analysis of sustained minimal residual disease (MRD) negativity from GRIFFIN. J Clin Oncol. 2022;40 (suppl_16):8011. doi: 10.1200/JCO.2022.40.16_suppl.8011

Among patients with newly diagnosed, transplant-eligible myeloma treated in a phase 2 study,  induction and consolidation  with daratumumab plus the RVd regimen outperformed RVd alone in terms of minimal residual disease and progression-free survival.

Daratumumab Added to RVd Achieved MRD Negativity, PFS Improvement in Newly Diagnosed Myeloma

In patients with myelofibrosis, including individuals with platelet counts lower than 50 × 10

/L, treatment with pacritinib (Vonjo) had a comparable or superior safety profile compared to best available therapy — including ruxolitinib (Jakafi), according to results presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

While JAK inhibitors remain a pillar in the myelofibrosis treatment paradigm, they have recently come under scrutiny for their toxicity. In an effort to find a drug for the patient population that is more tolerable, researchers recently analyzed pacritinib’s safety profile across two clinical trials: PERSIST-2 and PAC203.

“The safety analysis really tries to focus on these toxicities of interest for patients treated with pacritinib at 200 mg orally, twice daily and best available therapy, including ruxolitinib in the phase 2 and phase 3 studies,” said Naveen Pemmaraju, MD, study author and associate professor of Leukemia at The University of Texas MD Anderson Cancer Center, said while presenting the findings.

“Importantly, the aim of this analysis is to describe the safety profile of pacritinib 200 mg orally, including time on treatment.”

A total of 160 patients given pacritinib were included in the analysis (n = 106 from PERSIST and n = 54 from PAC203). Ninety-eight were in the best available therapy cohort, including 44 on ruxolitinib.

While data showed that there was a higher rate of adverse events for those on pacritinib (1570 per 100 patient-years at risk, compared to 903/100 patient-years at risk), the rate of fatal adverse events was lower. The incidence of bleeding or cardiac events was slightly lower for those given pacritinib compared to those given best available therapy (12/100 vs 22/100 patient-years at risk, respectively). There were no major adverse cardiac events in the pacritinib events, whereas there were 5 in the best available therapy group. Thrombosis was similar between the 2 arms.

Infection was more prevalent in the pacritinib cohort, but fungal and viral infections happened less frequently for these patients compared to the best available therapy cohort. Additionally herpes zoster reactivation occurred less frequently on the pacritinib arm than it did the best available therapy arm (0/11 patient-years vs 2.4/100 patient years, and 5.5/100 patient-years, in the pacritinib, best available therapy and ruxolitinib arms, respectively).

When it came to malignant neoplasms, there was a similar rate between the two arms, with a statistically significant lower risk of non-melanoma skin cancer in patients given pacritinib compared to best available therapy (3/100 patient-years, versus 7/100 patient-years, including 11/100 patient-years for those on ruxolitinib, respectively).

“In conclusion, in this novel, risk-adjusted analysis, this project demonstrated that the safety profile of pacritinib…is comparable to (best available therapy),” Pemmaraju said. “Pacritinib 200 mg may, indeed, represent a full-dose therapeutic option for patients with myelofibrosis, include for even those patients with (myelofibrosis) and thrombocytopenia.”

Pemmaraju N, Scott BL, Savona MR, et al. Risk-adjusted safety analysis of pacritinib (PAC) in patients (pts) with myelofibrosis (MF). J Clin Oncol 40, 2022 (suppl 16; abstr 7058)

An analysis presented during the 2022 ASCO Annual Meeting reveals that pacritinib's safety profile is comparable with beast available therapy, including ruxolitinib.

Pacritinib Displays Safety Profile Similar to Best Available Therapy in Myelofibrosis

The mutimodal interventional  therapy of lenvatinib (Lenvima), PD-1 inhibition, and transarterial therapy was safe and effective in patients with unresectable hepatocellular carcinoma (HCC), according to findings from a propensity score-match analysis presented in a poster at the European Association for the Study of the Liver’s 2022 Liver Cancer Summit.

“Transarterial chemoembolization [TACE] and hepatic arterial infusion chemotherapy [HAIC] are also recommended treatments for patients with intermediate to advanced HCC. Because HCC is a tumor with rich blood supply, TACE or HAIC can improve the concentration of chemotherapy drugs in the tumor, which can improve the curative effect on the one hand and reduce the systemic adverse events on the other hand. Clinical studies have confirmed that the ORR [overall response rate] of patients with intermediate HCC can be more than 50% with TACE alone,” said lead author Wei Lu, MD, PhD, of the Tianjin Medical Univer- sity Cancer Institute and Hospital in China, in an interview with 

The investigators conducted a retrospective study analyzing 70 patients with intermediate or advanced HCC who underwent therapy with len- vatinib, PD-1 inhibition, and transarterial therapy (LEN-PD1-TH) and compared outcomes with patients who only received lenvatinib and anti–PD-1therapy(LEN-PD1).Patientsweretreated at Tianjin Cancer Hospital between December 2018 and October 2020. The study’s primary end point was progression-free survival (PFS), with the secondary end points being overall survival (OS) and ORR.

At a median follow-up of 14 months (95% CI, 10.1-17.9), the LEN-PD1-TH group achieved a longer median PFS compared with the LEN-PD1 group, 15 months vs 9 months, respectively (

 =.004). OS was also improved, as the median OS was not reached in the LEN-PD1-TH cohort and was 14 months in the LEN-PD1 cohort (

ORR, as determined by modified RECIST criteris was significantly higher in the LEN-PD-1-TH group at 42.9% compared with the LEN-PD1 group at 20.1% (

 =.039). One patient in the LEN-PD1-TH group achieved a complete response and 14 patients had partial responses vs 7 with partial responses in the LEN-PD1 group; 9 patients had stable dis- ease in each group. By regular RECIST criteria, the ORRs were 28.6% and 22.9% in the LEN-PD1-TH and LEN-PD groups, respectively (

This study is the first to report that the efficacy of lenvatinib combined with PD-1 inhibitors and interventional therapy is better than that of lenvatinib combined with PD-1 inhibitors when the baseline level is balanced and the number of [participants] in the 2 groups is the same. Based on this, we hope our results can provide a theo- retical basis or enlightenment for future related research,” the authors wrote in the poster.

Subgroup analyses of the findings also showed that patients younger than 65 years who had liver cirrhosis, Child-Pugh class A, extrahepatic metastasis, no vascular invasion, tumors smaller than 10 cm and more than 3 tumors, Barcelona Clinic liver cancer stage C, and α-fetoprotein at or under 400 ng/mL were more likely to benefit from the 3-drug combination in terms of both PFS and OS. For all other patients, the LEN-PD1-TH and LEN-PD1 groups had comparable prognostic efficacy.

There were 70 patients included in the safety analysis, and the most common grade 3 or higher adverse event was hypertension in both treat- ment groups (17.1% and 20.0% in the LEN-PD1 and LEN-PD1-TH cohorts, respectively).

Because the most common adverse reaction of the combined regimen is hypertension, patients should pay attention to monitoring blood pressure and take oral antihyperten- sive drugs in time if blood pressure rises. In addition, timely review of blood routine, liver function, and other indicators can timely formulate treatment plans according to their own adverse reactions,” the authors wrote.

Investigators observed 2 grade 3 hand- foot-skin reactions and 1 grade 3 bleeding event in the LEN-PD1 group. In the LEN-PD1- TH group, there was 1 grade 3 decreased platelet count and 1 grade 3 muscle pain event. Ultimately, the investigators noted that there was not a significant difference in adverse events between the 2 groups.

Of note, patients enrolled in the study were prescribed 8 mg of daily lenvatinib instead of the standard dose of 12 mg to make the therapy more tolerable and ensure that they would complete as many treatment courses as possible.

Ultimately, the investigators are hoping that their findings lay the groundwork for future research regarding the combination use of lenvatinib, PD-1 therapy, and transarterial therapy.

“The next step is to continue to collect patients, expand cases, and continue follow-up. If possible, we intend to conduct prospective research to further verify our conclusions,” they said.

Lu W, Lang M, Song T, et al. Efficacy of combination therapy with lenvatinib, programmed cell death 1 inhibitors and transarterial therapy: a propensity score-matching cohort study. Presented at: EASL Liver Cancer Summit 2022; February 3-4, 2022; virtual. Ab- stract PO-119. 

Findings from the use of mutimodal interventional therapy of lenvatinib and transarterial therapy may lay the groundwork for future research regarding the combination for the treatment of patients with hepatocellular carcinoma.


Multimodal Therapy Explored in Unresectable HCC

Although prior research has suggested that daily aspirin use may have antitumor effects, a recent study found no difference in invasive disease–free survival between patients with HER2-negative breast cancer who took a full-strength aspirin daily and those who did not. “Although inflammation may still play a key role in cancer, it’s also important to remember that aspirin may have different effects in other cancers, such as colon, or in a different setting, such as primary vs secondary prevention,” study author Wendy Y. Chen, MD, MPH, a medical oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts, explained during a presentation of the data. 

The study (NCT02927249), which was presented at the February 2022 American Society of Clinical Oncology (ASCO) Plenary Series,

 included more than 3000 patients under 70 years with HER2-negative breast cancer who were randomly split into 2 groups: half received 300 mg of aspirin every day, and the other received a placebo (

 ). The main goal of the study was to compare invasive disease–free survival. “Aspirin users had a slightly worse survival than those patients who received placebo,” Chen said. Findings showed that the aspirin users had a higher amount of disease events than the placebo group (111 compared with 90, respectively), although the difference was not statistically significant and the types of events were relatively balanced between the 2 groups, the investigators explained. 

There was also a similar amount of severe AEs between the arms. “The incidence of grade 3 or higher [AEs] was similar for aspirin vs placebo. Further, there were no grade 4 cardiac, hematologic, or gastrointestinal events in the aspirin group,” Chen said. 

However, another expert involved in the ASCO Plenary Series noted that the characteristics of the patient population may play a role in the outcomes that were observed. “From these data, we can conclude that this high event rate among a postmenopausal, overweight population who had hormone receptor– positive, high-risk disease was to be expected. And this is exactly the group that one would want to try to intervene upon, because we’d expect this group to have high levels of inflammation,” said Angela DeMichele, MD, MSCE, coleader of the Breast Cancer Research Program and director of the Breast Cancer Clinical Trials Unit at Penn Medicine’s Abramson Cancer Center in Philadelphia, Pennsylvania. 

Additionally, DeMichele pointed out that about 44% of patients dropped out in the early stages of the trial, although the reasons why were not made known and could be interesting to consider. Study participants reported on whether they were adherent to taking their aspirin or placebo daily, and DeMichele noted, “Self-report can be notorious for overestimates of adherence.” 

Despite potential reasons for the poorer aspirin outcomes, this was not the first study to show that aspirin use may not improve cancer-related outcomes. 

In 2018, findings from the Aspirin in Reducing Events in Elderly trial (ASPREE; NCT01038583)1 were published, and they showed worse outcomes for patients who were over age 70 years and who took daily aspirin. 

“Aspirin users [in the ASPREE trial] were found to have an increased risk of death—that was mainly driven by increased risk of cancer deaths. Of note, 19% had a prior history of cancer,” Chen said. 

The United States Preventive Services Task Force recommends daily aspirin for the prevention of colorectal cancer in individuals aged 50 to 59 years who have a 10-year cardiovascular risk of 10% or higher. However, the jury is out when it comes to the risks and benefi ts of aspirin use in older adults. 

“What we can take away from this study... is that at this time, aspirin should not be used simply to prevent breast cancer recurrence. For those situations in which there are other options, decisions about aspirin use for other indications should include an individualized risk/benefit discussion between physician and patient,” DeMichele said. 

1. Chen WY, Ballman KV, Winer EP, et al. A randomized phase III, double-blinded, placebo-controlled trial of aspirin as adjuvant therapy for breast cancer (A011502): the aspirin after breast cancer (ABC) trial. Presented at: ASCO Plenary Series. Accessed February 24, 2022. https:// bit.ly/3haWSPZ

A recent study found no difference in invasive disease–free survival between patients with HER2-negative breast cancer who took a full-strength aspirin daily and those who did not.