Brittany Lovely

Tagrisso(osimertinib) combined with platinum-based therapy and pemetrexed (a type of chemotherapy) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS; time from treatment until death or disease worsening) compared with Tagrisso monotherapy in patients with 

-mutated advanced non–small cell lung cancer (NSCLC).

Tagrisso is a targeted medication that treats non-small-cell lung carcinomas with specific mutations.

Dr. Pasi A. Jänne, who is director of the Lowe Center for Thoracic Oncology, the Belfer Center for Applied Cancer Science, the Chen-Huang Center for EGFR Mutant Lung Cancers, and a senior physician at Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, in Boston, Massachusetts, presented findings from the phase 3 FLAURA2 study during the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.

Following a safety run-in, patients with untreated, locally advanced, metastatic 

-mutant NSCLC were randomly assigned to be treated with 80 mg of Tagrisso plus pemetrexed in combination with carboplatin, or to maintenance Tagrisso alone.

To be included, patients must be aged at least 18 or 20 years if residing in Japan with pathologically confirmed nonsquamous NSCLC with either an exon 19 deletion or L858R mutation, a World Health Organization (WHO) performance status of 0 or 1 and who had received no prior systemic therapy for advanced NSCLC. Those with stable central nervous system (CNS) metastases were permitted and all patients had to undergo a CT/MRI scan at baseline.

The median PFS via investigator assessment with the Tagrisso combination was 25.5 months vs 16.7 months with Tagrisso monotherapy translating to a 48% reduction in the risk of disease progression. The 12-month PFS rates were 80% and 66%, respectively, and the 24-month PFS rates were 57% vs 41% respectively.

The PFS benefit was observed across all subgroups.

“Tagrisso plus platinum/pemetrexed offers a new first-line treatment option for patients with advanced 

Jänne added that EGFR-TKIs are a standard first-line treatment for patients with 

-mutant advanced NSCLC, yet most patients will progress following treatment and clinical factors associated with poor prognosis include CNS metastases as well as the L858R mutation.

“Tagrisso, a third-generation, CNS active EGFR-TKI, is the preferred first-line treatment for 

-mutant advanced NSCLC based on superior PFS/OS benefit with Tagrisso vs (Iressa [gefitinib]) or (Tarceva [erlotinib]) in the FLAURA study.”

The primary end point was PFS, and secondary end points included overall survival (OS; time from treatment until death of any cause), duration of response (DOR), disease control rate, health-related quality of life, safety and time to second disease progression.

At baseline, patient characteristics were well balanced. In the Tagrisso/platinum/pemetrexed arm the median age was 61 years (range, 26-83), most patients were women (62%), Chinese Asian (25%) or non-Chinese Asian (39%), had a WHO performance status of 1 (62%), were never smokers (67%), had adenocarcinoma (99%), had metastatic disease (95%), had extra-thoracic metastases (53%) and 42% of patients had CNS metastases. 

 mutations were exon 19 deletions (61%) and L858R (38%). The baseline median tumor size was 57 mm (range, 10-284).

In the Tagrisso monotherapy arm the median age was 62 years (range, 30-85), most patients were women (61%), Chinese Asian (25%) or non-Chinese Asian (38%), had a WHO performance status of 1 (63%), were never smokers (65%), had adenocarcinoma (99%), had metastatic disease (97%), had extra-thoracic metastases (54%) and 40% of patients had CNS metastases. 

 mutations were exon 19 deletions (60%) and L858R (38%). The baseline median tumor size was 57 mm (range, 11-221).

At data cutoff, in the combination arm, 56% of patients and 25% of patients were still receiving treatment with Tagrisso and pemetrexed, respectively. Discontinuation rates were as follows: Tagrisso (44%) platinum (23%), and pemetrexed (75%). In the monotherapy arm 45% of patients were still receiving treatment at data cutoff, with 55% discontinuing Tagrisso.

Among patients with CNS metastases, those who received the Tagrisso combination had a median PFS of 24.9 months vs 13.8 months with Tagrisso monotherapy. Patients without CNS metastases in the combination armhad a median PFS of 27.6 months vs 21.0 months with Tagrisso monotherapy.

 exon 19 deletion who received the Tagrisso/pemetrexed/platinum chemotherapy was 27.9 months vs 19.4 months with Tagrisso monotherapy. Among those with an L858R mutation, those in the combination arm had a median PFS of 24.7 months vs 13.9 months in the monotherapy arm.

For CNS and EGFR status, the reviews were conducted via investigator analysis.

Time to second disease progression and OS were immature at the time of the analysis, with 34% and 27% maturity, respectively. The median time to second disease progression was 30.6 months with Tagrisso/pemetrexed/platinum chemotherapy vs 27.8 months with Tagrisso alone. The median OS was non-reactive in either arm.

At data cutoff, the discontinuation rate among those who had received subsequent anticancer therapy was 46% in the Tagrisso plus platinum/pemetrexed arm and 60% in the Tagrisso monotherapy arm. In both arms, cytotoxic chemotherapy was the most common second-line treatment which was administered in 65% and 82% of those who went on to receive anticancer treatment, respectively.

Tumor response was documented as best percentage change and objective response rate (ORR). Among 279 patients in the Tagrisso/pemetrexed/platinum arm the median best percentage change in target lesion size was –52.6% (range, –100.0 to 20.0). In the Tagrisso monotherapy, the median change was –50.0 (range, –100.0 to 40.4).

The ORRs were 83.2 vs 75.5% in the combination and monotherapy arms. One patient in the combination arm had a complete response, meaning that no cancer was found after treatment, and 83% had a partial response (PR). The complete and PR rates in the monotherapy arm were 1% and 75%, respectively. Stable disease lasting at least 35 days was reported in 12% and 18% of patients in the combination and monotherapy arms, respectively. Disease progression was observed in 3% and 4% of patients, respectively.

The median duration of response was 24 months in the combination arm and was 15.3 months in the monotherapy arm.

Investigators reported that the safety profiles were as expected for each treatment and were manageable with standard medical practice. The median total duration of Tagrisso exposure was 22.3 months (range 0.1-33.8) in the Tagrisso/platinum/pemetrexed arm and 19.3 months (range 0.1-33.8) in the Tagrisso monotherapy arm. In the combination arm, the median number of pemetrexed cycles was 12 (range 1-48) and 212 patients (77%) completed 4 cycles of platinum-based chemotherapy.

In the combination arm, side effects of any cause occurred in all patients, with 64% of patients experiencing a grade 3 or higher side effect, 7% having a side effect resulting in death, 38% experiencing a serious side effect, and 48% experiencing a side effect leading to discontinuation. When broken up by treatment, 11%, 17%, and 43% of patients had a side effect leading to discontinuation related to Tagrisso, carboplatin or cisplatin or pemetrexed, respectively.

In the monotherapy arm, side effects of any cause occurred in 97% of patients, with 27% experiencing a grade 3 or higher side effect, 3% having a side effect resulting in death, 19% experiencing a serious side effect and 6% experiencing a side effect leading to discontinuation.

Side effects deemed possible causally related to treatment were reported among 97% and 88% of patients in the combination and monotherapy arms with 53% and 11% of AEs being grade 3 or higher. The grade 3 or higher events in the combination arm were reported among 81 (29%) events with Tagrisso, 104 (38%) events with cisplatin or carboplatin and 130 (47%) events with pemetrexed. AEs leading to death were reported among 5 patients in the combination arm and 1 patient in the monotherapy arm. Serious side effects causally related to treatment were reported in 19% and 5% of patients in the combination and monotherapy arms, respectively.

The most common grade 1/2 side effectsin the combination arm were nausea (42%), diarrhea (41%), anemia (27%), constipation (29%), decreased appetite (28%), rash (28%), fatigue (25%), vomiting (25%), stomatitis (24%) and paronychia (23%). Grade 3 events included anemia (20%), neutropenia (19%) and thrombocytopenia (12%). Grade 4 events included neutropenia (4%), thrombocytopenia (2%), COVID-19 (< 1%) and white blood cell count decrease (< 1%).

In the monotherapy arm, the most common grade 1/2 side effects were diarrhea (40%), paronychia (26%), dry skin (24%) and rash (21%). Grade 3 events included decreased appetite (1%), neutropenia (1%), thrombocytopenia (1%), diarrhea (< 1%), fatigue (< 1%), stomatitis (< 1%), paronychia (< 1%), increase ALT level (< 1%), increase AST level (< 1%) and white blood cell count increase (< 1%). No grade 4 side effects were reported in the monotherapy arm.

Of note, any-grade interstitial lung disease, which was used as a grouped term, was reported in eight patients (3%) in the Tagrisso/platinum/pemetrexed arm and 10 patients (4%) in the Tagrisso monotherapy arm.

Investigators noted that ongoing analyses include CNS response and progression, post progression endpoints, patient-reported outcomes and subsequent therapies. Additionally, circulating tumor DNA (ctDNA) analyses will be used to identify resistance mechanisms and ctDNA dynamics.

In a discussion of the data, Dr. Yi-Long Wu, a professor at Guagndong Provincial People’s Hospital in China commended the investigators on the findings but cautioned the use of EGFR TKIs in combination with chemotherapy without OS data.

“The data showed that a longer PFS benefit comes with higher toxicity,” Wu said. “If the OS is positive, the FLAURA2 strategy will be the new standard of care for the 

-mutant first line. If the OS is negative (in) FLAURA2, it means the patient experiences the chemotherapy (AEs) early or for longer.” Wu also noted that the CNS data are intriguing and that resistance mechanisms may affect OS and require more clarity.

In a final question, Wu asked, “What do physicians and patients think about Tagrisso with chemotherapy?” In a survey study, results showed that physicians responded that chemotherapy would be tolerable, but that most patients do not agree. Among 71 physicians, 84.5% said that they would opt for the monotherapy option if resistance with the combination was only delayed by 10 months.

As for how long they would expect to prolong resistance before choosing the combination, 38% answered 12 months, 37% answered 18 months, 9.9% answered two years and 15.5% answered greater than two years. For patients, 72% would opt for the combination if it delayed resistance for 10 months. Patients and family said they would expect delays of 12 months (18%), 18 months (10%), two years (15%), or more than two years (57%) before choosing the combination.

“Should we need combination treatment for 

-mutant advanced NSCLC in the first-line setting? Yes, we need it. We need the combination treatment with more efficacy and less toxicity and (that is) convenient for (patients with) this disease,” Wu said.

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The three-drug combination of Tagrisso plus platinum-based chemotherapy and pemetrexed boosted outcomes for patients with EGFR-mutant advanced non-small cell lung cancer. 

Tagrisso Plus Platinum Therapy and Pemetrexed Improve Outcomes in Lung Cancer Subset

Patients with metastatic non-small cell lung cancer (NSCLC) experienced early antitumor activity when treated with the combination of Trodelvy (sacituzumab govitecan-hziy) and Keytruda (pembrolizumab) in a first-line setting, recent trial results have showed.

The objective response rate (ORR, measuring patients whose disease responded to treatment) was 56% and the confirmed partial response (PR, decrease in tumor size or extent of cancer) rate was 49% among 61 treated patients in two cohorts of the EVOKE-02 trial, data from which were presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer.

In cohort A, which included 29 patients with a tumor proportion score (TPS) of at least 50%, the ORR was 69%. The confirmed PR rate in this cohort was 62%. In cohort B, which included 32 patients with a TPS of less than 50%, the ORR was 44% and the confirmed PR rate was 38%.

“Patients with metastatic NSCLC continue to need novel treatment options. The data from the EVOKE-02 study gives us confidence in the clinical activity of (Trodelvy) in combination with (Keytruda) in first-line metastatic NSCLC patients,” Dr. Byoung Chul Cho said in a news release. Cho is a professor in the division of medical oncology at Yonsei Cancer Center, Yonsei University College of Medicine in South Korea. “The positive response rates and duration of response across patients treated with the combination shows promise compared with historical responses to anti-PD1 monotherapy in this setting. These data support further investigation of (Trodelvy) as a potential (immunotherapy)-combination option in first-line metastatic NSCLC.”

The phase 2 EVOKE-2 trial is evaluating whether the addition of the TROP-2–directed antibody-drug conjugate (ADC) Trodelvy can improve outcomes in the first-line setting with the PD-1 inhibitor Keytruda for patients with treatment-naïve metastatic NSCLC. The ongoing trial will ultimately evaluate the combination alone and with chemotherapy (cisplatin and carboplatin). A safety run-period is underway to determine the recommended dose for the chemotherapy cohorts.

Enrollment criteria included confirmed diagnosis of stage 4 NSCLC, measurable disease per RECIST 1.1 criteria, no known actionable genomic variants, an Eastern Cooperative Oncology Group (ECOG) performance status — assessing how a disease affects a patient’s daily living abilities — status of 0 or 1, and no prior treatment for metastatic NSCLC. Patients in cohorts A and B could have squamous or nonsquamous disease and were stratified by TPS status, whereas patients in the chemotherapy cohorts will be stratified by histology not TPS.

Patients in cohorts A and B received Trodelvy at 10 mg/kg intravenously on days 1 and 8 in combination with Keytruda 200 mg intravenously on day 1 of 21-day cycles. Trodelvy is administered until disease progression or unacceptable toxicity and Keytruda is given for up to 35 cycles. The primary end points are ORR, dose-limiting toxicities in the safety run-in phases, with secondary end points including disease control rate (DCR, patients whose disease shrunk, disappeared or is stable from treatment), duration of response (DOR), progression-free survival (the time a patient lives without the disease worsening), overall survival and safety.

At baseline, the median age of the 30 patients in cohort A was 67 years, 80% were male, most patients were White (73%), had an ECOG performance status of 1 (80%) and had nonsquamous histology (60%). Stage 4 disease was confirmed in 80% of patients, and five patients had stage 1, 2 or 3 disease.

Among the 33 patients in cohort B, the median age was 68, 79% were male, most patients were White (82%), had an ECOG performance status of 1 (76%), and had nonsquamous histology (61%). Stage 1, 2 or 3 disease was reported among 5 patients, with 85% having stage 4 disease at baseline. Per PD-L1 immunohistochemistry 22C3 pharmDx assay, PD-L1 TPS was 1% to 49% in 48% of patients and was less than 1% in 52% of patients.

The median duration of treatment in cohort A was 4.1 months with Trodelvy and 3.6 months with Keytruda. The median number of cycles was six for both agents, and 63% of patients are continuing treatment with both agents. The overall discontinuation rate was 37%.

In cohort B, the median duration of treatment with Trodelvy was 4.1 months and was 3.8 months for Keytruda. The median number of cycles was six for both agents. Patients are continuing to Trodelvy at a rate of 39% and 42% of patients are continuing treatment with pembrolizumab. Overall, 58% of patients have discontinued all study treatment. Investigators noted that discontinuation of Trodelvy was attributed to progressive disease (PD).

At a data cutoff of June 16, 2023, the median follow-up for cohort A was 5 months and was 5.8 months for cohort B. Additional efficacy findings showed that among all patients the DCR with the combination was 82%. The median DOR was not reached and the estimated DOR rate at 6 months was 87%. PD was observed in 8% of patients and stable disease (SD) was reported in 26%.

In cohort A, the DCR was 86% with the median DOR not reached and a six-month DOR rate of 88%. PD was reported among 10% of patients and SD among 17% of patients. In cohort B, the DCR was 78% with the median DOR not reached and a six-month DOR rate of 88%. PD and SD were reported at rates of 6% and 34%, respectively.

In terms of safety, any-grade treatment emergent side effects were reported in all 63 patients in the safety cohort, with 90% related to study treatment. Grade 3 or higher side effects were reported in 70% of patients and 38% were related to study treatment. Serious side effects occurred at a rate of 54% with 14% attributed to study treatment. Discontinuation of Trodelvy due to side effects was reported among 14% of patients and 13% of patients discontinued Keytruda due to side effects. Dose reductions were reported for 18% of patients who received Trodelvy. Four deaths were reported due to side effects and included malignant lung neoplasm, respiratory tract infection and sudden death, with sepsis reported as a death related to study treatment.

The most common grade 1/2 side effects included diarrhea (51%), anemia (low red blood cells, 42%), asthenia (weakness, 38%), alopecia (loss of hair, 37%), nausea (30%), constipation (24%), appetite decrease (22%), respiratory tract infection (20%), fatigue (19%), mucosal inflammation (18%), dyspnea (difficulty breathing, 17%) and neutropenia (low numbers of neutrophils, a type of white blood cells, 9%).

Grade 3 or higher side effects included neutropenia (18%), anemia (6%), respiratory tract infection (5%), dyspnea (5%), diarrhea (3%) and fatigue (2%).

Immune-mediated side effects of grade 1/2 included pneumonitis (5%), hyperthyroidism (5%), colitis (2%) and hypothyroidism (2%). Grade 3 or higher immune-mediated side effects included pneumonitis (3%), colitis (2%), nephritis (2%), and maculopapular rash (2%). Investigators noted these were consistent with the known safety profile of Keytruda.

“These preliminary results warrant further investigation of (Trodelvy) and (Keytruda) for the first-line treatment of metastatic NSCLC,” investigators wrote in their conclusions.

Next steps include the ongoing, open label, global, randomized, phase 3 EVOKE 03 trial, which is evaluating Trodelvy and Keytruda vs Keytruda monotherapy as a first-line treatment for patients with metastatic NSCLC with PD-L1 TPS of at least 50%.

Data revealed promising results for the combination of Trodelvy and Keytruda as a first-line treatment for patients with metastatic non-small cell lung cancer.

Trodelvy Plus Keytruda Shows Antitumor Activity in NSCLC

Adolescent and young adult patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia experienced varying outcomes when treated with pediatric-inspired protocols and adult chemotherapy regiments such as hyperCVAD/MA. 

Adolescent and young adult (AYA) patients with Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) experienced varying outcomes when treated with pediatric-inspired protocols (PIPs) and adult chemotherapy regimens such as hyperCVAD/MA (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, alternating with methotrexate and cytarabine), according to data presented at the Society of Hematologic Oncology 2023 Annual Meeting.

The two-year event-free survival (EFS, the time following treatment where a patient experiences no cancer-related complications) was 65.8% — 80.6% for patients who received PIP and 52.6% for patients treated with hyperCVAD.

Among the 103 total evaluable patients in the single-center retrospective review, the two-year recurrence-free survival (RFS, the time following treatment without any signs or symptoms of cancer) was 75.6%, in which 93.7% of patients received PIP and 59.6% of patients received hyperCVAD.

HyperCVAD/MA is a regimen used for the treatment of adult patients with Ph-negative ALL. Pediatric patients, however, receive modified treatments, most of which feature higher doses of asparaginase (a chemotherapy drug) and corticosteroids (an anti-inflammatory medication).In the analysis, investigators compared treatment outcomes of 57 patients treated with hyperCVAD with 56 patients treated with a PIP across the phase 2 CALGB 10403 trial and the phase 3 GRAALL-2005 trial.

Although overall survival (OS, the time a patient lives following treatment) outcomes were numerically improved among those who received a PIP vs. hyperCVAD, the difference was not statistically significant, explained Omar Shahin, who presented the data during the meeting. The two-year OS rate for all treated patients was 72.2%, with patients in the PIP group having a two-year OS rate of 80.3% vs. 65.7% for those in the hyperCVAD arm.

“Pediatric-based treatment protocols lead to better two-year EFS and RFS than hyperCVAD for AYA patients with Ph-negative ALL … (and) prospective trials comparing both adult treatment and PIPs are warranted,” Shahin, a medical oncologist at the King Hussein King Hussein Cancer Foundation and Center in Cairo, Jordan said. “Over the past decades, researchers have identified a distinct group known as AYAs with ages between 15 and 39 years. This group has higher survival rates than adults but lower rates than children (and) this (has) prompted many research groups to evaluate pediatric-inspired regimens in the treatment of AYA patients with ALL.”

Shahin showed that in an analysis of SEER data, the five-year survival rates of patients with ALL aged younger than 15 years was 92.1% compared with 77% among those aged 15 to 19 years, 66.8% among those aged 20 to 39 years and 43% among those aged 40 to 64 years.

The analysis evaluated outcomes from patients ages 18 to 39 years treated at King Hussein Cancer Center between 2010 and 2022. Shahin noted that baseline characteristics were well-balanced between the groups. Overall, most patients were men (77.9%), had T-cell ALL (63.8%) or B-cell ALL (36.2%), and cytogenetic risk factors as follows: diploid (51.3%), other (16.8%), failed (11.5%), unknown (20.4%). High-risk disease was reported in 4.4% of patients.

A notable difference was observed in age. Among those who were treated with a PIP, the median age was 23 years vs. 27 years for those who received hyperCVAD. This was deemed significant.

“Looking at secondary outcomes, almost 93% of all patients (92.8%) achieved complete remission (CR) at the end of induction with no difference between the groups and we had eight (patients with) refractory disease distributed evenly between the hyperCVAD group and the PIP (group),” Shahin said.

Other outcomes included 22.5% of patients having relapse, with 22 patients who received hyperCVAD (38.6%) experiencing disease relapse versus three patients in the PIP group (5.6%) for a statistically significant difference. Extramedullary (outside of the bone marrow) relapse occurred in the central nervous system in five patients, all of whom were in the hyperCVAD group. Other sites of extramedullary relapse included skin, lymph nodes, lungs and testicular sites and were reported in four patients in the hyperCVAD group (7%) and two patients in the PIP group (3.7%).

Overall, 23.9% of patients received allogeneic stem cell transplant, which included 16 patients in the hyperCVAD group and 11 patients in the PIP group. Among the 27 patients, the primary indications for proceeded to transplant were high-risk characteristics, refractory disease, relapse or unknown. None of these were statistically significant between the groups.

Outcomes at last follow-up deemed statistically significant included CR and relapse. In the hyperCVAD group, the CR rate at last follow-up was 71.9% compared with 89.1% in the PIP group. The relapse rate was 28.1% vs. 7.3% in the hyperCVAD and PIP groups, respectively.

“We had two unfortunate deaths during induction, and both of those occurred during induction with PIP, one (because of) liver failure and cerebral hemorrhage and one (because of) septic shock,” Shahin said. “We had 11 deaths during CR occurring during maintenance or consolidation distributed evenly between both the groups with no significant difference (and) most of these death(s) occurred (because) of neutropenic complications, with (others attributed to) COVID-19 and GVHD (graft-vs-host disease).”

Varying outcomes among adolescent and young adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia treated with pediatric-inspired protocols or adult chemotherapy regimens warrant further study.

AYA Patients With Acute Lymphoblastic Leukemia Treated With Pediatric or Adult Regimens Saw Mixed Results

The biology of a patient and when treatment is initiated — rather than a patient’s risk stratification features — may best determine the appropriate frontline treatment for patients with clear cell renal cell carcinoma (RCC), an expert said.

Dr. Thomas Powels discussed this topic in a presentation during the 2023 Kidney Cancer Research Summit.

The [International Metastatic Renal Cell Carcinoma Database Consortium] classification is a fantastic prognostic indicator — good, intermediate and poor — and it works across broad subgroups of patients; but it doesn’t represent accurate biology,” Powels, director of Barts Cancer Center and professor of urology cancer at Barts Cancer Institute in London, England, said in a presentation during the 2023 Kidney Cancer Research Summit. “Within the biology of the good, the intermediate and the poorest disease, there will be responses to angiogenic therapy, to immune therapy, to both and (possibly) CTLA-4 as well. This is relatively important because if you think you’re selecting the biology of the patient for good-risk disease, that would be an inaccuracy.”

Powels added that classification is dynamic from the patient perspective, meaning that after patients under nephrectomy minimal residual disease is present, which may push patients into one classification over another. “With this biology of good, intermediate and poor (classifications), we know that those good-risk patients have more angiogenic signatures, but it’s not complete, and the poor patients have more immune type signatures. But again, that’s not complete,” Powels explained of understanding the full story of a patient’s biology and risk. “If you think that patients with good risk are all the same, that will be inaccurate, because just like cars, some cars go faster than others. And it depends on where the patients are in that journey, and how fast their cancers growing.”

Further, Powels pointed to how the timing of diagnosis is also relevant to the International Metastatic Renal Cell Carcinoma Database Consortium classification. “Those with aggressive biology, they go from good to intermediate to poor very quickly,” he said. “Then you’ve got an intermediate and a slow biology (where the tumor burden increases slower). In the slowest biology, patients may never get to poorest disease. But at snapshots in time, patients can be at different parts on the track.”

These International Metastatic Renal Cell Carcinoma Database Consortium and biology should be noted when considering available treatment options, but also depending on when treatment is initiated, clinicians should be aware that patients may shift International Metastatic Renal Cell Carcinoma Database Consortium classification based on response, Powels added. “I want you to think about it as a two-dimensional, not a one-dimensional picture of biology and time of presentation.”

Treatment Options for Patients With Clear Cell RCC

 has demonstrated that treatment with the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) has improved overall and progression-free survival (the time during and after treatment that a patient with cancer lives without disease worsening) for patients with intermediate/poor-risk disease versus Sutent (sunitinib). The median overall survival (the time when a patient with cancer is still alive) was 47 months with the immunotherapy combination (425 patients) versus 26.6 months with Sutent (422 patients). The 60-month overall survival rates were 43% and 31%, respectively. The median progression-free survival was 11.6 months in the investigative arm versus 8.3 months in the control arm. The 60-month progression-free survival rates were 31% and 11%, respectively.

“(These data are) transformative, (the combination) clearly beats (Sutent) out of the park,” Powels said.

Cross-trial comparisons require a bit more context, Powels said. For example, in terms of response, the conversations around response need to take into context that approximately 40% of patients’ response to Opdivo/Yervoy, he said. “If 75% of those (responses) are durable, that would then be 30% (overall). (The same could be said of) a VEGF TKI with a (durable) response rate of 60%. ... So, when you’re being told things about duration of response and some of these secondary or exploratory end points, I think it’s very important to put them in context, because we’re very liberal about how we throw the conversations around in this (ongoing) debate.”

In an example, Powels noted five-year follow-up 

 of Keytruda (pembrolizumab) plus Inlyta (axitinib) versus Sutent demonstrate how VEGF/PD-1 dual inhibition has good initial control of disease, which is important for some patients, whereas the Opdivo/Yervoy data may look less desirable for those with good risk disease, but over time, the efficacy does appear to catch up in terms of response and progression-free survival.

For KEYNOTE-426 specifically, the median overall survival was 47.2 months with the combination (432 patients) versus 40.8 months in the control arm (429 patients). The 60-month overall survival rate was 41.9% versus 37.1%, respectively. For progression-free survival, the median in the Keytruda/Inlyta arm was 15.7 months versus 11.1 months in the Sutent arm, with 60-month progression-free survival rates of 18.3% and 7.3%, respectively.

Adding to this landscape are data from the final prespecified analysis of the 

. In the trial, patients with clear cell RCC were randomly assigned to the investigative arm of Lenvima (lenvatinib) plus Keytruda or Afinitor (everolimus) or the control arm of Sutent. The median overall survival was 53.7 months with the combination of Lenvima plus Keytruda (355 patients) versus 54.3 months with Sutent (357 patients). The 36-month overall survival rate was 66.4% versus 60.2%, respectively.

A continued progression-free survival benefit was observed with the combination of Lenvima and Keytruda at 23.9 months versus 9.2 months with Sutent. The 36-month progression-free survival rates were 37.3% versus 17.6%, respectively.

data from the phase 3 CheckMate 9ER trial

, the median overall survival with the investigational regimen of Opdivo and Cabometyx (cabozantinib) was 49.5 months versus 35.5 months with Sutent.

“I think this issue around comparing the trials, which we like to do … and I think we’re creating inaccuracies in some of the things we say, and I’m including myself with this debate,” Powels said. “Essentially, we have four good options, all of which have beaten (Sutent) with more similarities than differences. The best duration of these therapies is undefined. CTLA-4 is likely to help but we haven’t defined exactly how much it helps yet. Good risk disease is complicated. We need to focus on that the trials are hard to do they take longer and therefore (we) aren’t doing them. But I worry those patients may get left behind.”

An expert explained what aspects of a patient’s disease cancer care teams use to determine the best treatment options for patients with clear cell renal cell carcinoma. 

Brittany Lovely

Tagrisso Plus Platinum Therapy and Pemetrexed Improve Outcomes in Lung Cancer Subset

Trodelvy Plus Keytruda Shows Antitumor Activity in NSCLC

AYA Patients With Acute Lymphoblastic Leukemia Treated With Pediatric or Adult Regimens Saw Mixed Results

How Cancer Teams Leverage Biology in Guiding First-Line Therapy for Clear Cell RCC

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