The nomogram, a new prognostic tool, has exhibited a capability to predict outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC) after treatment with lutetium-177 (177Lu) prostate-specific-membrane antigen (PSMA). Researchers hope this new tool could be useful in informing future trial designs and clinical decisions, according to data from a retrospective study published in 

The nomograms, which were developed by investigators at the UCLA Jonsson Comprehensive Cancer Center and those from 5 other institutions, included predictive variables, such as the time since initial diagnosis of prostate cancer, chemotherapy status, hemoglobin concentration at baseline, and [68Ga]Ga-PSMA-11 PET/CT parameters such as molecular imaging TNM classification and tumor burden.

Results from the study showed that the C-index of the overall survival (OS) model was 0.71 (95% CI, 0.69-0.73). Similar C-indices were observed with internal validation (0.71; 95% CI, 0.69-0.73) and external validation (0.72; 95% CI, 0.68-0.76). Moreover, the C-index for the prostate-specific antigen (PSA) progression-free survival (PFS) model was 0.70 (95% CI, 0.68-0.72). Again, similar C-indices were achieved with both internal (0.70; 95% CI, 0.68-0.72) and external (0.71; 95% CI, 0.68-0.74) validation. As such, both models were found to have acceptable calibration with predictions that correlated with observed outcomes.

“Until now, there has been no validated tool to adequately predict the response of patients with advanced metastatic prostate cancer to Lu-PSMA treatment,” said lead author Andrei Gafita, MD, a postdoctoral scholar in the Ahmanson Translational Theranostics Division of the department of molecular and medical pharmacology at the David Geffen School of Medicine, said in a press release.2 “Most important, this study suggests that screening with PSMA PET imaging could help to select patients who are most likely to benefit from this treatment.”

177Lu-PSMA is a radiolabeled small molecule inhibitor that binds with high affinity to PSMA and delivers β particle radiation. In June 2021, the FDA granted a breakthrough therapy designation to the agent based on results from the phase 3 VISION trial (NCT03511664), which demonstrated that when combined with standard-of-care treatment, 177Lu-PSMA resulted in a 40% reduction in the risk of death vs SOC alone in patients with progressive PSMA-positive mCRPC.

Although many efforts have been made to understand tumor heterogeneity and to develop prognostic nomograms in patients with mCRPC who receive frontline or second-line treatment, no models exist to efficiently evaluate the prognosis for patients who are later in their disease course and are potentially eligible for treatment with 177Lu-PSMA. As such, investigators sought to develop nomograms as a way to predict outcomes with the therapy in this population.

For the multicenter, retrospective study, predictive nomograms were developed using data collected from 6 institutions across the United States, Germany, and Australia—all of whom had screened patient who had received treatment with 177Lu-PSMA from December 10, 2014, to July 19, 2019, as part of a phase 2 clinical trial (NCT03042312, ACTRN12615000912583).

To be eligible, patients had to have received an intravenous injection of 177Lu-PSMA, at a dose ranging from 6.0 GBq to 8.5 GBq once every 6 to 8 weeks for a maximum of 4 to 6 cycles, without experiencing disease progression or notable toxicity. Additionally, patients had to have a [68Ga]Ga-PSMA-11 PET/CT scan, clinical data, and information on survival outcomes available. Patients who received 18F-labeled PSMA-PET at baseline were excluded.

Overall, 270 were enrolled to the trial; these patients were assigned to a development cohort for model development (n = 196) or a validation cohort for model validation (n = 74). The primary outcomes for the nomograms were OS and PSA-PFS.

Data on 26 different pretherapeutic parameters were collected from patients, 18 of which were tested in models as putative predictors of outcome after treatment with 177Lu-PSMA. Some of the pretherapeutic parameters included information on demographics, initial diagnosis of prostate cancer, treatment history, baseline clinical status, baseline laboratory tests, and baseline [68Ga]Ga- PSMA-11 PET/CT tumor characteristics.

Among the 270 patients included, the median age across the cohorts was 71 years (range, 65-76), and the median time since initial diagnosis was 6.5 years (range, 4-12). Fifty-eight percent of patients had received treatment with 177Lu-PSMA as part of compassionate access programs, and 42% had received the therapy as part of a clinical trial. The therapy was administered for a median of 3 cycles per patient. Patients had received a median of 3 prior systemic treatments, with 95% having received treatment with second-generation antiandrogens and 81% having previously received chemotherapy.

At a median follow-up of 21.5 months, 83% of the 270 patients had died and 91% experienced PSA progression.

Additional data from the study indicated that the estimated 12-month OS rate was 54% (95% CI, 48%-60%), and the estimated 18-month OS rate was 34% (95% CI, 29%-40%). Predictors selected in this model included time since cancer diagnosis, chemotherapy status, baseline hemoglobin concentration, bone and liver involvement status, number of metastatic lesions, and tumor SUVmean.

Moreover, the estimated 3-month PSA-PFS rate was 64% (95% CI, 58%-70%); at 6 months, the estimated rate was 38% (95% CI, 32%-43%). Selected predictors for this model were time since cancer diagnosis, chemotherapy status, pelvic nodal status, bone and liver involvement status, and tumor SUVmean.

Additionally, patients in the development cohort, the validation cohort, and the complete set were stratified into 2 risk groups using the calculated optimal cutoff for the risk scores; this was 197 points for the OS nomogram and 178 points for the PSA-PFS nomogram.

In the development cohort, the median OS for low- vs high-risk patients were 19.1 months (95% CI, 17.1-21.1) and 8.4 months (95% CI, 7.4-9.4), respectively (

<.0001). The median PSA-PFS in this cohort was 9.4 months (95% CI, 6.6-12.1) in patients who were high risk vs 3.3 months (95% CI, 2.9-3.7) in low-risk patients (

In the validation cohort, patients who were low risk were found to have a significantly longer median OS than those who were high risk, at 24.9 months (95% CI, 16.8-27.3) vs 7.4 months (95% CI, 4.0-10.8), respectively (

<.0001); this was also true with regard to PSA-PFS, at 6.6 months (95% CI, 6.0-7.1) vs 2.5 months (95% CI, 1.2-3.8), respectively (

In complete set, the median OS for low- and high-risk patients were 19.9 months (95% CI, 17.5-22.3) vs 8.2 months (95% CI, 7.2-9.1), respectively (

<.0001). The median PSA-PFS in these subsets were 8.8 months (95% CI, 7.3-10.3) vs 3.3 months (95% CI, 2.8-3.7), respectively (

“The findings from the research are encouraging and may provide the foundation for patient selection for LuPSMA therapy,” Gafita said. “Nevertheless, until its clinical validity is demonstrated in prospective trials, the tool should be used cautiously and should not replace the clinical judgement of treating physicians.”

Gafita A, Calais J, Grogan TR, et al. Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. 

. Published online July 8, 2021. doi:10.1016/S1470-2045(21)00274-6

Tool helps predict who will respond best to targeted prostate cancer therapy. News release. UCLA. July 8, 2021. Accessed July 21, 2021. 

Novartis receives FDA breakthrough designation for investigational 177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC). News release. Novartis. June 16, 2021. Accessed July 21, 2021. 

Morris MJ, De Bono JS, Chi KN, et al. Phase III study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). 

. 2021;39(suppl 15):LBA4. doi:10.1200/JCO.2021.39.15

This article was originally published on OncLive as “New Tool Could Help Predict Outcomes with 177Lu-PSMA in Metastatic Castration-Resistant Prostate Cancer”

Articles

Nomogram May Have the Power to Predict Treatment Outcomes in Patients with Prostate Cancer Subtype 

Data from the prospective COVIDSurg-Cancer study (NCT04384926) demonstrated that patients with urological cancer who were infected with COVID-19 were more likely to develop respiratory complications and to be at an increased risk of dying following elective surgery for their disease, compared to patients with urological cancer who had not contracted the virus. 

The study results, which were presented during the 36th Annual European Association of Urology (EAU) Congress, demonstrated that those with SARS-CoV-2 positivity were significantly more likely to experience postoperative respiratory complications such as adult respiratory distress syndrome (n = 3; 21.4%; P < .01), pneumonia (n = 4; 28.6%; P < .01), oxygen therapy (n = 10; 71.4%; P < .01), and pulmonary embolism (n = 1; 7.1%; P < .01) within 30 days of their operation.


Moreover, 2 of 412 patients (0.5%) who did not have the virus died within 30 days following their surgical procedure vs 3 of 14 patients (21.4%) with COVID-19 (P <.01). The rates of postoperative Clavien-Dindo Grade III+ complications were 1.7% (n = 2/119), 7.6% (n = 4/53), and 3.3% (n = 2/61) for nephrectomy, cystectomy, and prostatectomy, respectively.


In the international, multicenter, prospective, observational study, investigators set out to examine the impact of the COVID-19 pandemic on the 30-day outcomes of patients with urological cancers such as kidney cancer, bladder cancer, and prostate cancer, who had undergone elective cancer surgery.


To be included, patients must have been planned for curative cancer surgery and underwent the procedure during the pandemic or they had their procedure delayed or cancelled during the pandemic.


Patients needed to be at least 18 years of age and have a confirmed diagnosis of an included cancer type. They could not have surgery planned with non-curative intent. Moreover, patients could not have planned neoadjuvant therapy without a set date for surgery, nor could they be awaiting restaging.


The primary outcome measure for the trial was mortality within 30 days, and key secondary outcomes comprised COVID-19 infections, respiratory complications, and postoperative complications within 30 days.


Prospective data from 436 consecutive patients with urological cancer were collected from several centers between March 11, 2020, and April 19, 2020. Of those patients, 39.7% had kidney and upper tract urothelial cancer (UTUC; n = 173), 28.9% had bladder cancer (n = 126), and 31.4% had prostate cancer (n = 137).


Of the 173 patients with kidney cancer and UTUC, 172 underwent elective cancer surgery. The majority, or 98.8% (n = 170) of these patients were alive at 30 days after the procedure, but 2 patients died. One of the patients who died (50.0%) were positive for COVID-19.


Among the 126 patients with bladder cancer, 120 underwent surgery; 115 patients were alive at 30 days and 3 had died at that time point. Two of the 3 patients (66.6%) who died had COVID-19. Of the 137 patients with prostate cancer, all patients received elective cancer surgery and no patients died at 30 days.


“To continue elective cancer surgery throughout future waves of the pandemic, it would be sensible to take precautions to minimize the risk of patients developing COVID-19 perioperatively,” lead study author Chuanyu Gao, of the British Urology Researchers in Surgical Training, and colleagues, concluded.


1.	Gao C. Characteristics and 30-day outcomes for urological cancer patients operated on during the COVID-19 pandemic. Presented at: 36th Annual European Association of Urology (EAU) Congress; July 9-12, 2021; virtual. Abstract P0186. https://bit.ly/2TNz6l3
2.	Outcomes of elective cancer surgery during the COVID-19 pandemic crisis (CovidSurg-Can). ClinicalTrials.gov. Updated May 12, 2020. Accessed July 10, 2021. https://clinicaltrials.gov/ct2/show/NCT04384926
This article was originally published on OncLive as “Patients With Urological Cancer and COVID-19 Undergoing Elective Surgery at Higher Risk for Mortality”


This article was originally published on OncLive as 

“Patients With Urological Cancer and COVID-19 Undergoing Elective Surgery at Higher Risk for Mortality”

A diagnosis of COVID-19 was associated with an increased risk of respiratory problems and mortality in patients with urological cancer undergoing elective procedures for their disease. 

 COVID-19 Heightens Mortality Risk in Patients with Urological Cancer Undergoing Elective Procedures

Frontline lenvatinib (Lenvima) plus pembrolizumab (Keytruda) has been labeled a “standout option” by Robert J. Motzer, MD, for the treatment of patients with advanced renal cell carcinoma (RCC). Data from a recent clinical trial demonstrated that the combination induced superior progression-free survival, as well as improved quality of life, compared to sunitinib (Sutent) alone.

Results from the phase 3 CLEAR trial (NCT02811861) presented during the 

 showed that the median progression-free survival (PFS) with lenvatinib/pembrolizumab was 23.9 months (95% CI, 20.8-27.7) vs 14.7 months (95% CI, 11.1-16.7) with lenvatinib and everolimus (Afinitor) and 9.2 months (95% CI, 6.0-11.0) with sunitinib.

The stratified hazard ratio with lenvatinib/pembrolizumab vs sunitinib was 0.66 (95% CI, 0.49-0.88; 

Lenvatinib plus pembrolizumab was also found to showcase similar or improved HRQoL and disease-related symptom scores compared with sunitinib, and lenvatinib plus everolimus was found to have similar or worse HRQoL and symptom scores vs those observed with sunitinib.

“The quality-of-life assessments are the perception of a patient. The HRQoL assessments are filled out by the patient on how they perceive their tolerability to the regimen, and how they feel about being on the regimen,” Motzer said. “They are an extraordinarily important metric that needs to be considered seriously when interpreting results of trials, and choosing a regimen.”

Earlier data from the trial supported the submission of a biologics license application for pembrolizumab and a supplemental new drug application for lenvatinib for the frontline treatment of patients with advanced RCC. In May 2021, the FDA granted priority review to the applications in May 2021.

In an interview with Oncology Nursing News®’ sister publication, OncLive®, Motzer, medical oncologist, Kidney Cancer Section head in the Genitourinary Oncology Service, and the Jack and Dorothy Byrne Chair in Clinical Oncology at Memorial Sloan Kettering Cancer Center, discussed the efficacy and HRQoL benefits of lenvatinib/pembrolizumab in patients with advanced RCC, and projected where the regimen might fit into the treatment paradigm.

®: Could you speak to the rationale of conducting the HRQoL analysis of the CLEAR trial?

: CLEAR was a 3-arm trial that compared pembrolizumab plus lenvatinib with everolimus plus lenvatinib, and [then compared] both of those arms with sunitinib in patients with clear cell RCC as a first-line therapy.

Results showed that both lenvatinib-containing arms met their primary end point, showing improvement in progression-free survival [PFS] compared with sunitinib. [However,] only the lenvatinib/pembrolizumab [arm] showed an increase in overall survival [OS]; the results for lenvatinib plus everolimus compared with sunitinib were similar.

The efficacy observed in this trial was quite striking—particularly for the lenvatinib plus pembrolizumab arm, with a very high response rate of over 70%, a 16% complete response rate, and a median PFS of approximately 24 months. The safety profile was as anticipated for both arms compared with sunitinib. The results presented during the 2021 ASCO Annual Meeting [focused on] HRQoL [outcomes].

What is your expectation for where the combination of pembrolizumab plus lenvatinib will fit into the RCC treatment landscape? How will this regimen impact subsequent treatment use?

We have been successful in the past few years, in terms of developing better regimens [for the] first-line treatment [of patients with] RCC. [This success is] largely based on the [emergence of] newer TKIs, [such as] axitinib [Inlyta], lenvatinib, cabozantinib [Cabometyx], and the use of immunotherapy. [This includes] both immunotherapy combinations, such as ipilimumab [Yervoy] and nivolumab [Opdivo], and more recently, TKI/immunotherapy combinations. Results [with these combinations] have been very striking. [These regimens] have come about in a very short time, but clearly, all these options are better than a single-agent TKI.

However, we are still sorting out whether there is a role for one vs the other, or which regimen might be best or particularly useful for a community oncologist to administer. We studied lenvatinib plus pembrolizumab at our center in a large, single-arm trial of over 140 patients and I had personal experience with that regimen. It really appeared to be an excellent regimen in terms of efficacy and manageable safety.

What I was most impressed with in the phase 3 trial is the magnitude of efficacy that we saw, coupled with manageable toxicity. It is a standout [option] for use in first-line therapy, and certainly, along with the others, it should be a choice [in this setting].

Do any subgroups appear to derive more benefit with this treatment regimen than others?

With the lenvatinib/pembrolizumab regimen, one of its best features are that it seems to be effective across the board. [We see efficacy] in patients, regardless of risk group. The favorable-risk patients did very well with [this approach], as well as the intermediate- and the poor-risk patients. Those who had sarcomatoid elements also did very well [with the doublet]. It is a very reliable regimen, [for which we know that] we are going to see a positive effect.

What were the key findings from the HRQoL analysis of the trial?

We performed several analyses. In a mixed-model analysis, we looked at longitudinal changes from baseline to [time] on study. In the other [analysis], we looked at time to deterioration, which was one end point [of the trial], as well as time until definitive deterioration, which served as another end point. [Results from the] QoL studies suggested that [these end points] were either similar or better with some scales with [regard to] lenvatinib plus pembrolizumab compared with sunitinib.

The time until definitive deterioration was the standout [finding because it was] in favor of lenvatinib plus pembrolizumab. The hallmark of that analysis is that it looks at QoL, by these scales, over time. As such, patients who continue on the trial, even those who were treated beyond progression or those with a [long] PFS, appear to, over time, have a better QoL.

In general, I would say that the scores were the same, or better, with lenvatinib plus pembrolizumab. On the other side of the coin, when we looked at lenvatinib plus everolimus, for the most part, the scores were either the same or worse [than what we saw with sunitinib]. This makes sense because the combination is comprised of 2 targeted therapies, and there is a fair amount of toxicity that has been associated with it. The results were quite fitting with what we have seen in terms of efficacy and safety for both of these regimens [in the past].

What is the take-home message from this research?

The standout from the overall trial was the efficacy gain [observed with] lenvatinib plus pembrolizumab. Those results were extremely impressive, and [demonstrate that this regimen] is a good choice for the first-line treatment [of patients with] RCC. The toxicity was certainly manageable with lenvatinib plus pembrolizumab. In my own experience, is that over time, the toxicities are quite manageable with dose reduction, as needed. Patients can stay on treatment for long periods of time. I have patients who were treated on this program for years. Those metrics are assessed by clinicians and research staff.

[However, we always need to ask ourselves,] how does the patient feel about [the regimen]? I was quite impressed that this [efficacious] combination had either similar or better scores than what we have seen with sunitinib, which has been our standard of care for more than a decade.

Motzer RJ, Porta C, Alekseev B, et al. Health-related quality-of-life (HRQoL) analysis from the phase 3 CLEAR trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) or everolimus (EVE) versus sunitinib (SUN) for patients (pts) with advanced renal cell carcinoma (aRCC). 

. 2021;39(suppl 15):4502. doi:10.1200/JCO.2021.39.15_suppl.4502

Merck and Eisai receive priority review from FDA for KEYTRUDA (pembrolizumab) plus LENVIMA (lenvatinib) applications for advanced renal cell carcinoma and for advanced endometrial carcinoma. News release. Merck. May 6, 2021. Accessed July 9, 2021. https://bit.ly/2PYnqtM

“Lenvatinib/Pembrolizumab’s Favorable HRQoL Leads to “Standout” Option for Frontline RCC”

The efficacy and health-related quality of life benefits associated with the combination of lenvatinib and pembrolizumab make it a favorable treatment for advanced renal cell carcinoma, says an expert from Memorial Sloan Kettering Cancer Center. 

Lenvatinib-Pembrolizumab Combo Induces ‘Impressive’ Results in Patients with Advanced Kidney Cancer

 demonstrated that men with positive pelvic lymph nodes or a prostatectomy Gleason score of 8 to 10 with disease extending beyond the prostate benefited from adjuvant radiation therapy and that the treatment was associated with a significant reduction of all-cause mortality in this population.

After investigators excluded patients with adverse pathology who had persistent prostate-specific antigen (PSA) expression, the reduced risk of all-cause mortality (ACM) associated with adjuvant radiotherapy remained significant vs early salvage radiation therapy. The association was maintained regardless of whether patients had pelvic nodal involvement (HR, 0.33; 95% CI, 0.13-0.85; 

 = .02) or not (HR, 0.66; 95% CI, 0.44-0.99; 

“We found that among men with adverse pathology at radical prostatectomy including pN1 or prostatectomy Gleason score 8-10 and pT3a or higher PC, adjuvant compared with early salvage radiotherapy was associated with a significant reduction in ACM risk,” the authors of the study wrote. “This association of reduced ACM risk with adjuvant compared with early salvage radiotherapy is strengthened given that men who underwent adjuvant compared with early salvage radiotherapy had less favorable prostate cancer prognostic factor distributions, which should have placed them at higher risk for needing salvage androgen deprivation and dying.”

Patients with prostate cancer who have adverse pathology at radical prostatectomy continue to be at a high risk for recurrence.

 This includes patients with pelvic node–positive disease, prostatectomy Gleason scores of 8 through 10, and extra-prostatic extension or seminal vesicle invasion or invasion into neighboring organs. When this patient population experiences recurrence, their PSA is found to rapidly increase, rising from the trigger PSA level of 0.1 ng/mL or 0.2 ng/mL to 0.4 ng/mL, signifying progression; this can happen while salvage radiotherapy is being planned and delivered, and before PSA response to salvage radiation therapy can be evaluated.

This results in men experiencing progression earlier while on salvage radiotherapy vs adjuvant radiotherapy. Due to this, investigators set out to determine whether those with adverse pathology at radical prostatectomy could derive benefit from adjuvant treatment vs salvage.

The study had a cohort of 26,118 men who had a median age of 62 years (range, 57-67) with pT2-4N0 or N1M0 prostate cancer that had been consecutively treated between June 23, 1989 and July 26, 2016. This treatment needed to include radical prostatectomy and pelvic lymph node assessment, after which patients were followed for possible treatment with adjuvant or early salvage radiotherapy.

The study took place at several institutions, including University Hospital Hamburg-Eppendorf; Charité University Hospital; University Hospital Ulm; University of California, San Francisco; and Johns Hopkins Medical Institution. Patients included in the study were stratified based on the presence or absence of adverse pathology.

Of the patients who were included in the study, 3.14% (n = 819) received adjuvant radiotherapy generally within 6 months of radical prostatectomy and 17.72% (n = 4601) received salvage radiotherapy. The 2 groups had PSA levels of less than 0.1 ng/mL and a median of 0.30 ng/mL, respectively. Among those in the salvage radiotherapy group, 14.24% (n = 655) had persistent PSA levels, defined as a postoperative PSA of 0.1 ng/mL or greater, and were categorized into the early salvage radiotherapy group. Additionally, adjuvant and salvage androgen deprivation therapy were administered in 1.35% and 9.69% of patients, respectively.

After receiving radical prostatectomy to the prostatic bed at a median dose of 68.4 Gy and pelvic lymph nodes (45.0 Gy), adjuvant radiotherapy was delivered a median of 3.55 months. Moreover, adjuvant androgen deprivation therapy was administered for a median of 9.17 months. In total, 5.71% (n = 1491) of the study population had pelvic lymph node–positive disease, of which 21.4% were treated with adjuvant radiotherapy and 16.16% received adjuvant androgen deprivation therapy. Notably, salvage androgen deprivation therapy was administered following PSA failure and clinical or radiographic evidence of progression following adjuvant or salvage radiotherapy.

“Men who received neither adjuvant radiotherapy nor early salvage radiotherapy never experienced PSA failure during the conduct of the study or were treated with salvage androgen deprivation therapy alone at progression,” wrote the authors of the study.

Those with adverse pathology who underwent adjuvant radiotherapy over salvage radiotherapy had a notably higher proportion of pT3a or higher (97.90% and 94.48%, respectively; 

 = .002) and margin-positive disease (82.71% and 45.68%, respectively; 

< .001). Additionally, those who received adjuvant therapy had a significantly higher proportion of patients with margin-positive disease (88.07% and 45.17%; 

< .001) and less use of salvage androgen deprivation therapy (35.78% and 45.84%; 

 = .06) vs early salvage radiotherapy with adverse pathology excluding pN1.

After a median follow-up of 8.16 years (range, 6.00-12.10), investigators reported that 8.06% (n = 2104) of the study population had died, 25.62% (n = 539) of whom passed from prostate cancer. Other findings from the study indicated that there was a significant association identified wherein adjuvant treatment decreased risk of all-cause mortality in men with positive margins (HR, 0.55; 95% CI, 0.34-0.90; 

 = .02) over salvage radiotherapy, although the significance was lost when excluding men with persistent PSA (HR, 0.67; 95% CI, 0.37-1.001; 

 = .0504). No significant association was observed in men without adverse pathology at radical prostatectomy (

Among those with adverse pathology including pN1 who received adjuvant radiotherapy, no radiotherapy, and salvage radiotherapy, investigators reported a 10-year adjusted point estimate for all cause morbidity of 13.78% (95% CI, 8.43%-22.12%), 27.32% (95% CI, 22.54%-32.88%), and 21.98% (95% CI, 18.30%-26.27%), respectively. When excluding pN1, the estimates were 5.13% (95% CI, 2.00%-12.82%), 25.32% (95% CI, 18.95%-33.34%), and 22.15% (95% CI, 17.55%-27.74%), respectively. Moreover, when excluding patients with adverse pathology, the estimates were 7.82% (95% CI, 4.55%-13.28%), 8.81 (95% CI, 7.35%-10.54%), and 7.95% (95% CI, 6.82%-9.24%).

“In conclusion, three randomized trials and a meta-analysis found no difference in progression-free survival for adjuvant compared with early salvage radiotherapy use. However, a benefit might have been missed in men with adverse pathology at radical prostatectomy because of inadequate power and the presence of immortal time bias,” the authors concluded.

Tilki D, Chen Ming-Hui, Wu J, et al. Adjuvant versus early salvage radiation therapy for men at high risk for recurrence following radical prostatectomy for prostate cancer and the risk of death. 

. Published online June 4, 2021. doi:10.1200/JCO.20.03714

Markowski MC, Chen Y, Feng Z, et al. PSA doubling time and absolute PSA predict metastasis-free survival in men with biochemically recurrent prostate cancer after radical prostatectomy. 

. 2019;17(6):P470-475. doi:10.1016/j.clgc.2019.08.002

Suissa S. Immortal time bias in pharmacoepidemiology. 

. 2007;167(4):492-499. doi:10.1093/aje/kwm324

Parker CC, Clarke NW, Cook AD, et al. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. 

. 2020;396(10260):14131421. doi:10.1016/S0140-6736(20)31553-1

“Adjuvant Radiation Therapy Could Yield Reduction in All-Cause Mortality in High-Risk Prostate Cancer”

Adjuvant radiation therapy treatment yielded strong results in reducing all-cause mortality in patients with high-risk prostate cancer. 

Adjuvant Radiation Therapy Associated with Reduced Risk of Death in High-Risk Prostate Cancer

Findings from an exposure-response (ER) analysis of the phase 3 CheckMate 9ER trial (NCT03141177) showed that Cabozantinib (Cabometyx) did not result with an improved progression-free survival (PFS) but instead was associated with higher rates of plantar erythrodysesthesia (PPE) and diarrhea in patients with advanced renal cell carcinoma (RCC). 

“ER modeling predicts that appropriate dose modification of the 40-mg cabozantinib starting dose to manage AEs [adverse effects] will not adversely affect the efficacy of nivolumab plus cabozantinib in first-line advanced RCC,” lead study author Amishi Y. Shah, MD, an assistant professor in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and co-authors wrote in a poster of the data.

The CheckMate 9ER trial revealed that the frontline combination of nivolumab plus cabozantinib significantly improved PFS (HR, 0.51; 95% CI, 0.41-0.64; 

 < .001), overall survival (OS; HR, 0.60; 95% CI, 0.40-0.89; 

 < .001) compared with sunitinib (Sutent) in patients with advanced RCC.

In the study, patients with previously untreated RCC received 40 mg of cabozantinib daily in combination with 240 mg of nivolumab every 2 weeks.

The regimen was generally well tolerated among patients, with low rates of treatment-related discontinuations. Dose modifications appeared to successfully manage AEs and allow patients to tolerate the regimen.

Patients (n = 320) received a median average daily dose of 29.4 mg of cabozantinib in the CheckMate 9ER trial. First-level dose reductions of cabozantinib to 20 mg daily because of AEs were observed in 50% (n = 161) of patients after a median time of 98 days (range, 9-506). Second-level dose reductions of cabozantinib to 20 mg every 2 days were observed in 8.1% of patients (n = 26) after a median time of 173 days (range, 65-613).

Because of AEs, 7.5% of patients (n = 24) discontinued cabozantinib, 6.6% of patients (n = 21) discontinued nivolumab, and 5.6% of patients (n = 18) discontinued both agents.

With a database lock date of March 30, 2020, investigators sought to understand the relationship between cabozantinib exposure, and the efficacy and safety outcomes observed in the CheckMate 9ER trial utilizing time-to-event Cox proportional hazard ER models.

The models evaluated specified end points, including PFS, dose modifications (holds or reductions), and select AEs, such as grade 1 or greater PPE, grade 3 or greater diarrhea, grade 3 or greater hypertension, grade 3 or greater fatigue/asthenia, and grade 3 or greater alanine aminotransferase (ALT)/aspartate aminotransferase (AST) increase.

“Cabozantinib exposure was defined as the overall average concentration from time zero to time of event or censoring [CAVG0T] for each end point and estimated by population pharmacokinetic modeling,” Shah and co-authors wrote.

As of the database lock date, survival data were immature, so the relationship between OS and cabozantinib exposure was not assessed.

Regarding end points, the number of patients at risk receiving 1 or more doses of cabozantinib were 311 for PFS, 318 for dose modification, 320 each for PPE, diarrhea, hypertension, and fatigue/asthenia, and 317 for ALT/AST elevation. Of these, the number of patients with 1 or more measurable cabozantinib concentration was 303 for PFS, 306 for dose modification, 308 each for PPE, diarrhea, hypertension, and fatigue/asthenia, and 307 for ALT/AST elevation.

Regarding the number of events by end point, the number of patients receiving at least 1 dose of cabozantinib was 144 for PFS, 285 for dose modification, 128 for PPE, 22 for diarrhea, 44 for hypertension, 24 for fatigue/asthenia, and 35 for ALT/AST elevation. Of these, patients with at least 1 measurable cabozantinib concentration included 139 for PFS, 279 for dose modification, 128 for PPE, 21 for diarrhea, 44 for hypertension, 23 for fatigue/asthenia, and 34 for ALT/AST elevation.

In evaluable populations, patients were a median age of 62 years (range, 29-90), with a median body weight of 80.3 kg (range, 36.0-159.3), and the majority of patients (77%) were male with high Karnofsky Performance Statuses (≥90, 79%) and low lactase dehydrogenase (≤1.5 x upper limit of normal, 94%). The median nivolumab clearance was 0.009 L/h (range, 16.0-53.4).

The target lesions were a median of 69 mm (range, 10-330). Most patients did not have prior radiotherapy (86%) but underwent prior nephrectomy (69%).

Most patients (65%) were randomized to treatment in the CheckMate 9ER trial less than 1 year from initial diagnosis.

The majority of patients (74%) had a baseline PD-L1 status of less than 1% or an indeterminate status and International Metastatic RCC Database Consortium (IMDC) scores of 1 or 2 (58%).

In the PFS analysis population (n = 303), more favorable IMDC scores were observed in patients in higher exposure quartiles. However, baseline characteristics were generally similar otherwise.

Further results revealed that cabozantinib exhibited higher interpatient variability in apparent clearance (n = 306; median 1.93 L/h; range, 0.64-10.3) and average exposure (n = 303; median 564.6 ng/mL; range, 29.3-1995).

With regard to PFS, the median exposure in quartile 4 was 848.1 ng/mL (HR relative to CAVG0T, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 302.3 ng/mL (HR, 0.99; 95% CI, 0.71-1.40) in quartile 1, 485 ng/mL (HR, 1.00; 95% CI, 0.79-1.25) in quartile 2, and 641.2 ng/mL (HR, 1.00; 95% CI, 0.88-1.14) in quartile 3. Overall, this suggested that PFS was not different between cabozantinib exposure quartiles.

Regarding the development of grade 1 or greater PPE, the median exposure in quartile 4 was 872.1 ng/mL (HR relative to CAVG0T, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 318.9 ng/mL (HR, 0.51; 95% CI, 0.37-0.70) in quartile 1, 512.5 ng/mL (HR, 0.65; 95% CI, 0.53-0.80) in quartile 2, and 658.6 ng/mL (HR, 0.77; 95% CI, 0.68-0.87) in quartile 3.

Regarding the development of grade 3 or higher diarrhea, the median exposure in quartile 4 was 825.1 ng/mL (HR relative to CAVG0T, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 312.2 ng/mL (HR, 0.38; 95% CI, 0.19-0.75) in quartile 1, 471.2 ng/mL (HR, 0.51; 95% CI, 0.32-0.82) in quartile 2, and 606.9 ng/mL (HR, 0.66; 95% CI, 0.49-0.88) in quartile 3.

“The risk of developing PPE or diarrhea was greater at higher cabozantinib exposure quartiles; there was not association for hypertension, fatigue/asthenia, or AST/ALT elevation,” wrote Shah and co-authors.

Regarding dose modifications, the median exposure was 2.96 L/h in clearance quartile 4 (HR relative to CL/F, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 1.32 L/h (HR, 1.20; 95% CI, 0.91-1.57) in quartile 1, 1.74 L/h (HR, 1.13; 95% CI, 0.94-1.35) in quartile 2, and 2.19 L/h (HR, 1.07; 95% CI, 0.97-1.18) in quartile 3.

“The risk of cabozantinib dose modification increased with decreasing cabozantinib clearance but was not significantly different between cabozantinib clearance quartiles,” Shah and co-authors wrote.

Additionally, cabozantinib exposure was not found to be a statistically significant predictor of PFS, and the rate of progression or death was not significantly associated with daily cabozantinib exposure (20 mg vs 40 mg). CAVG0T was 386 ng/mL at the 20 mg daily dose vs 772 ng/mL at the 40 mg daily dose (HR, 1.00; 95% CI, 0.78-1.27).

Increased cabozantinib exposure was significantly associated with an increased risk of PPE (HR, 0.63; 95% CI, 0.50-0.78) and diarrhea (HR, 0.48; 95% CI, 0.29-0.80), but no significant exposure-response relationships were identified for hypertension, fatigue/asthenia, or ALT/AST elevation.

Although not statistically significant, higher cabozantinib clearance was associated with a lower rate of cabozantinib dose modification (2.2 L/h vs 1.2 L/h; HR, 0.87; 95% CI, 0.71-1.07; 3.2 L/h vs 1.2 L/h; HR, 0.80; 95% CI, 0.57-1.12).

A multivariable analysis with backward elimination showed that certain baseline patient characteristics, including sex, nivolumab clearance, and baseline albumin, were significant covariates. Patients with higher baseline nivolumab clearance or lower baseline albumin levels were predicted to have higher rates of disease progression or death.

Shah AY, Motzer RJ, Apolo AB, et al. Cabozantinib exposure-response analysis for the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. 

 2021;39(suppl 15):4561. doi:10.1200/JCO.2021.39.15_suppl.4561

This article was originally published as 

“Cabozantinib Exposure Not Associated With PFS, But Is Linked With Higher AEs With Cabozantinib/Nivolumab in RCC”

A presentation from the 2021 ASCO Annual Meeting highlights the current limitations of Cabozantinib as a treatment for RCC. 

Cabozantinib Did Not Improve PFS in CheckMate -9ER Exposure-Response Analysis and Results in More AEs in Patients with RCC 

Updated findings from a phase 2 study (NCT03401788) presented during the 2021 ASCO Annual Meeting revealed that patients with Von-Hippel Lindau (VHL)-associated renal cell carcinoma (RCC), as well as other VHL-associated neoplasm, showed significant clinical responses to the hypoxia-inducible factor-2 alpha inhibitor belzutifan.

“This update continues to demonstrate the activity of belzutifan in patients with VHL-associated renal and non-renal tumors accompanied by an acceptable safety profile,” said lead study author Ramaprasad Srinivasan, MD, PhD, head of the Molecular Cancer Therapeutics Section, Center for Cancer Research, National Cancer Institute.

Recently, the FDA granted belzutifan a priority review for the treatment of patients with VHL disease–associated RCC who do not require immediate surgery based on earlier results of this study.

The open-label, single-arm study enrolled 61 patients who were diagnosed with VHL disease based on germline alteration who had at least 1 measurable RCC tumor, had not received any prior systemic anticancer therapy, did not have metastatic disease, and had an ECOG performance status of 0 or 1. Patients were treated with 120 mg oral daily belzutifan as a potential systemic treatment for VHL-associated RCC and other VHL neoplasms.

Objective response rate (ORR) in RCC tumors per RECIST criteria by independent review committee was the primary end point and secondary end points included ORR in non-RCC neoplasms, duration of response (DOR), and safety.

The median age was 41 years (range, 19-66) at baseline and the majority of patients were male (52.5%) and had an ECOG performance status of 0 (82.0%). Pancreatic lesions were also reported in all patients, 36.1% of which were neuroendocrine; central nervous system (CNS) hemangioblastomas were reported in 82.0% of patients and retinal lesions in 26.2%.

As of data cutoff, a median of 21.8 months (range, 20.2-30.1) after enrollment, 88.5% of patients were still receiving treatment.

Responses in target RCC lesions were observed in 30 patients (49.2%; 95% CI, 36.1%-62.3%) of patients by independent review committee; all responses were partial responses (PRs), and another 4 patients had unconfirmed PRs. Stable disease was reported in 49.2% of patients and 1 patient was not evaluable. Ninety-two percent of patients had a decrease in target RCC lesion size.

The median time to response was 8.2 months (range, 2.7-19.1) and the duration of response was not reached (range, 2.8+ to 22.3+). Progression-free survival rate at 12 months was 98.3% and 96.5% at 24 months, and the median has not yet been reached.

In pancreatic lesions, responses were reported in 77.0% (95% CI, 64.5%-86.8%), with complete responses (CRs) in 9.8% and PRs in 67.2%. Among pancreatic neuroendocrine tumors, the ORR was

90.9% (95% CI, 70.8%-98.9%) with CRs in 13.6% and PRs in 77.3%. The ORR was 30.0% (95% CI, 17.9%-44.6%) in CNS hemangioblastomas with CRs in 6.0% and PRs in 24.0%.

Srinivasan noted that retinal hemangioblastomas were not amenable to classic response evaluation with RECIST criteria. Sixty-nine percent of retinal hemangioblastomas were improved and 31% were stable as best response.

All patients reported a treatment-related adverse event (TRAE) of any grade, grade 3 events were observed in 32.8% and grade 4 or 5 events in 14.8%. TRAEs led to discontinuation in 1.6% of patients and an adverse event led to death in 1 patient, but the event was not treatment related.

The most common AEs of any grade were anemia (90.2%), fatigue (65.6%), headache (41.0%), dizziness (39.3%), and nausea (34.4%). Most of the events were grade 1 or 2, but common grade 3 events were anemia (8.2%) and hypertension (8.2%). Srinivasan said that anemia was a predicted on-target effect of HIF-2–dependent downregulation of erythropoietin.

Srinivasan R, Donskov F, Iliopoulos O, et al. Phase 2 study of belzutifan (MK-6482), an oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). 

. 2021;39(suppl 15):4555. doi:10.1200/JCO.2021.39.15_suppl.4555

Merck Receives Priority Review from FDA for New Drug Application for HIF-2α Inhibitor Belzutifan (MK-6482). News release. Merck. March 16, 2021. Accessed June 7, 2021. https://bit.ly/38NLYM2

This article was originally published on OncLive as “Frontline Belzutifan Showcases Significant Clinical Activity in VHL-Associated RCC”

A phase 2 study reported clinical efficacy from the use of frontline belzutifan in patients with Von-Hippel Lindau (VHL). 

  Frontline Belzutifan Associated with Meaningful Clinical Activity in Treatment of VHL-Associated RCC

Telaglenastat (CB-839) did not produce a significant improvement in progression-free survival (PFS) when administered in conjunction with cabozantinib (Cabometyx) to treat metastatic renal cell carcinoma (mRCC). Despite these results, Nizar Tannir, MD, FACP, says telaglenastat may still produce positive results when combined with other therapeutic partners in a biomarker-selected populations with a high dependence on glutamine/glutaminase.

Results from the phase 2 CANTATA trial (NCT03428217), which were presented during the 

, showed that the combination yielded a median of 9.2 months (95% CI, 7.6-11.1) vs 9.3 months (95% CI, 7.6-11.0) with cabozantinib alone (hazard ratio [HR], 0.94; 95% CI, 0.74-1.21; 

 = .653) in this patient population (n = 444). Moreover, the overall response rate (ORR) was 31.2% with the combination vs 27.8% with cabozantinib alone, which was also not determined to be statistically significant.

“One should not be discouraged by a negative trial. So many agents have very strong [preclinical] rationale, they show encouraging results in phase 1 [trials], and then in large, randomized phase 3 trials, they end up being negative,” Tannir said. “It shows that we still have a long way to go [in terms of selecting] the proper patient population [for this regimen, and maybe, bringing back the concept of a biomarker-driven trial.”

®, Tannir, a professor in the Department of Genitourinary Medical Oncology, Division of Cancer Medicine, and Ransom Horne, Jr. Professorship for Cancer Research, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discussed the results of the phase 2 CANTATA trial with telaglenastat plus cabozantinib and future research directions for the glutaminase inhibitor.

®: Could you speak to the rationale for evaluating telaglenastat in the CANTATA trial?

: [Many research efforts] have focused on targeted therapy. For example, in kidney cancer, [we know that] angiogenesis is important. [We also know the] importance of immune checkpoint inhibitors in many tumor types. [However,] tumor metabolism has emerged as an important area of research.

If we look at normal cells, [they] produce energy through glucose conversion, through the glycolysis mechanism, and by producing adenosine triphosphate [ATP] in the tricarboxylic acid cycle [TCA] cycle. Tumor cells, on the other hand, must rely on [a pathway] other than the glucose pathway for their metabolism, because there is conversion of glucose to lactate through the Warburg effect; that is where glutamine comes [in].

Telaglenastat is a glutaminase inhibitor that blocks the conversion of glutamine to glutaminase. Many tumor types rely on glutamine and glutaminase to produce their energy. This is the rationale for producing this agent.

Additionally, phase 1 trial [NCT02071862] combined 

 in a small number of heavily pretreated patients. We observed an ORR of 50% and a disease control rate of 100% with the regimen. This provided a good foundation to conduct this large, phase 3 trial.

What was the design of the study, and the key objectives of the research?

[CANTATA] is a large global, randomized, placebo-controlled, double-blind phase 3 trial. [Investigators] looked at combining an agent that is FDA approved in the salvage setting, the VEGF TKI cabozantinib, [with telaglenastat]. It is a rational combination based on data from preclinical studies, [which] showed the combination of everolimus [Afinitor] plus telaglenastat, [as well as] the combination of cabozantinib plus telaglenastat, had synergy in both in vitro [and] in vivo models. That is the scientific rationale for this combination.

The design [of the trial] was simple; [we evaluated] telaglenastat plus cabozantinib vs placebo plus cabozantinib in the second- and third-line treatment setting. Patients had to have received [prior treatment with] either nivolumab [Opdivo] plus ipilimumab [Yervoy] or antiangiogenic inhibitors, and up to 2 prior lines of therapy. Participants were randomized [in a] 1:1 [fashion]. The primary end point of the study was PFS. The trial was powered to answer the question of whether the combination of telaglenastat plus cabozantinib could produce an improvement in PFS, as assessed by an independent radiology committee [IRC]. A [total] of 444 patients were accrued to the trial.

[Additionally,] there were some assumptions [to note], which first started with the control arm. We know that in the phase 3 METEOR trial [NCT01865747], which compared single-agent cabozantinib with everolimus in the second- and third-line setting and beyond, [results showed a] median PFS of 7.4 months. As such, there were assumptions made for this trial to design it and calculate the sample size. We used 8 months as the median PFS for the control arm, and the HR was set at 0.69; that is how we came up with 444 [as our target number of patients to accrue to the trial].

What were the results that read out during the 2021 ASCO Annual Meeting?

Unfortunately, results did not show an improvement in PFS with the combination of telaglenastat plus cabozantinib compared with placebo plus cabozantinib. The median PFS by IRC assessment in both arms proved to be very similar, at 9.2 months and 9.3. months, [respectively]; this shows that there is really no advantage or [PFS] benefit [derived from] the [experimental] combination. The data regarding responses to treatment were consistent [with this finding]; the ORR was 31% in the experimental arm vs 28% in the placebo arm, so no real difference between the arms.

[In terms of] overall survival [OS], most patients were still alive at the time of the analysis, or at the time of data cutoff, which was August 31, 2020. [Approximately] 35% of the patients had died on the experimental arm vs [approximately] 31% on the placebo arm. [The OS data are still] considered to be immature. In the future, we will have longer follow-up data from the study to assess OS. However, in terms of the primary end point of PFS, no difference [was observed] between the 2 arms.

What did the safety profile of the combination look like?

Data from a prior phase 1 trial [NCT02071862] that examined telaglenastat alone in heavily pretreated patients demonstrated a very tolerable profile, with very few adverse effects [AEs] reported; these effects were mostly grade 1 or 2. [Common AEs included] nausea, fatigue, photophobia, a slight elevation in liver function tests, diarrhea, and rash, [which are] typical [toxicities that we see with] targeted agents. Overall, the agent was well tolerated, and had a low discontinuation rate.

In terms of the AEs in CANTATA, they were very comparable between the arms. Any-grade AEs [were reported in about 99% of patients] in both arms, [and they] were consistent with either agent when it is given alone. The notable grade 3 AEs were diarrhea and hypertension; these were driven mostly by cabozantinib. [In terms of the] discontinuation rate, 10% of patients discontinued therapy in the experimental arm vs 15% in the placebo arm, and [approximately 80% of patients] required a dose interruption or reduction of cabozantinib on both arms.

What are your thoughts on why the trial turned out to be negative?

This [trial] obviously [had] an unselected patient population; it [was] not based on biomarkers. Why did the telaglenastat plus cabozantinib combination not show superiority in terms of PFS compared with placebo plus cabozantinib? Was the partner, cabozantinib, not the correct partner? If we go back to the hypothesis, which is tumor metabolism, is blocking the glutamine pathway relevant in oncology? I do believe it is. There is a high expression of this enzyme in many tumor types, and there are strong preclinical data in vitro and in vivo to suggest that this is a relevant pathway in oncology and tumor metabolism. [However,] could another agent combined with telaglenastat show a positive result?

[Data from a previous phase 2] study, [ENTRATA; NCT03163667], were presented during the 2019 ESMO Congress. Here, everolimus was combined with telaglenastat and compared with placebo plus everolimus. [This was a] smaller study of 69 patients; it had a similar design, [but] a 2:1 randomization. In that study, the PFS was also the primary end point, and the medium PFS was doubled with telaglenastat plus everolimus in a very heavily pretreated patient population, at 3.8 months vs 1.9 months with placebo plus everolimus. [As such, in terms of] blocking glucose and glutamine, these 2 pathways are important in tumor metabolism; [these data proved that] the hypothesis was correct. However, maybe the CANTATA study was negative because cabozantinib may not have been the best partner for [telaglenastat].

Where should future efforts be focused with telaglenastat?

Thinking forward, [we could evaluate the regimen in] a more selected patient population with tumors that are more metabolically driven rather than unselected [patients with] clear cell RCC. It is important to mention that there is a phase 2 study [NCT04265534] combining telaglenastat with chemotherapy in patients with nonsquamous non–small cell lung cancer that are driven by a mutation. Therefore, maybe in that patient population that is biomarker selected, we will see positive results. [Additionally,] some other ideas are being formulated to see whether we can test the same combination in other rare tumors of the kidney.

Tannir N, Agarwal N, Porta C, et al. CANTATA: Primary analysis of a global, randomized, placebo (Pbo)-controlled, double-blind trial of telaglenastat (CB-839) + cabozantinib versus Pbo + cabozantinib in advanced/metastatic renal cell carcinoma (mRCC) patients (pts) who progressed on immune checkpoint inhibitor (ICI) or anti-angiogenic therapies. 

. 2021;39(supp 15):4501. doi:10.1200/JCO.2021.39.15_suppl.4501

“Telaglenastat/Cabozantinib Does Not Significantly Improve PFS in Metastatic RCC, But Future Directions Hold Promise”

The results of the phase 2 CANTATA trial indicate that the combination of telaglenastat/cabozantinib does not significantly improve PFS, however, telaglenastat might still prove effective in certain populations. 

Telaglenastat Plus Cabozantinib Fails to Improve PFS in Metastatic RCC, But Still Holds Promise 

Treating patients with metastatic renal cell carcinoma (mRCC) with both pembrolizumab (Keytruda) and cabozantinib (Cabometyx) at the recommended phase 2 dose with a manageable safety profile (RP2D) resulted in a response in more than half of the participants and met its primary end point, according to a presentation on the phase 1/2 trial (NCT03149822) during the 2021 ASCO Annual Meeting.

The combination of drugs resulted in a response from more than half of patients. 

Genitourinary Cancer