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New data from the IMvigor130 trial have augmented oncologists’ knowledge about the treatment of locally advanced or metastatic urothelial carcinoma (mUC) with the immune checkpoint inhibitor atezolizumab.

Alan P. Lyss, MD
Dr. Alan P. Lyss

A second interim overall survival (OS) analysis suggested that atezolizumab monotherapy provides a clinical benefit as first-line treatment for mUC patients with PD-L1–expressing immune cells representing at least 5% of the tumor area (IC2/3), including patients who are cisplatin ineligible.

The analysis also suggested that atezolizumab plus chemotherapy produces similar OS results as chemotherapy plus placebo, but patients receiving atezolizumab may do better with cisplatin-based chemotherapy than with carboplatin-based chemotherapy.

These results were reported in two presentations at the American Association for Cancer Research Annual Meeting 2021: Week 1.

Current guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology recommend atezolizumab monotherapy for cisplatin-ineligible patients with mUC and PD-L1 IC2/3.

The ongoing phase 3 IMvigor130 trial was designed to compare atezolizumab plus gemcitabine/platinum chemotherapy, atezolizumab monotherapy, and placebo plus chemotherapy. Platinum-based chemotherapy included either cisplatin or carboplatin, per investigator choice.

Coprimary endpoints for IMvigor130 were progression-free survival (PFS) and OS for atezolizumab plus chemotherapy versus placebo plus chemotherapy. The hierarchical study design dictated that OS would only be assessed for the comparison of atezolizumab monotherapy versus placebo-chemotherapy in the overall and PD-L1 IC2/3 populations if there was statistical improvement in OS for the atezolizumab-chemotherapy arm over the placebo-chemotherapy arm.

Secondary endpoints were overall response rate (ORR; per RECIST 1.1), duration of response (DOR) for all patients, and PFS for the comparison between atezolizumab monotherapy and placebo-chemotherapy. Exploratory analyses were performed on cisplatin-ineligible patients by PD-L1 status.

At the time of the primary analysis, an OS benefit for atezolizumab-chemotherapy over placebo-chemotherapy was not observed. Therefore, the OS benefit of atezolizumab monotherapy versus placebo-chemotherapy was not assessed. However, a trend toward improved OS was noted with atezolizumab for PD-L1 IC2/3 patients, including cisplatin-ineligible patients.
 

Atezolizumab vs. placebo-chemo

Ian D. Davis, MBBS, PhD, of Monash University in Melbourne, presented the second interim analysis of OS with atezolizumab monotherapy versus placebo plus chemotherapy (Abstract CT040).

The median follow-up was 14.9 months for atezolizumab monotherapy (n = 360) and 11.8 months for placebo-chemotherapy (n = 359). The median OS was 15.2 months and 13.1 months, respectively (hazard ratio, 0.99; 95% confidence interval, 0.83-1.19). There was no apparent OS benefit of atezolizumab for any clinically selected subgroup.

The ORR was 23.4% for atezolizumab monotherapy and 44.1% for placebo-chemotherapy. The median DOR was more than 3.5 times longer for atezolizumab monotherapy than for placebo-chemotherapy – 29.6 months and 8.1 months, respectively.

Although there was no formal statistical comparison, exploratory subgroup analyses demonstrated that the median OS for the PD-L1 IC2/3 patients appeared higher in the atezolizumab monotherapy arm than in the placebo-chemotherapy arm – 27.5 months and 16.7 months, respectively.

Similarly, the median OS for cisplatin-ineligible PD-L1 IC2/3 patients appeared higher for atezolizumab monotherapy than for placebo-chemotherapy – 18.6 months and 10.0 months, respectively.

In terms of safety, atezolizumab monotherapy compared favorably with placebo plus chemotherapy. There were similar numbers of grade 3/4 adverse events and comparable adverse events leading to discontinuation of treatment in both arms.

The atezolizumab monotherapy arm had fewer adverse events leading to withdrawal from any treatment, when compared with the placebo-chemotherapy arm – 7% and 34%, respectively. Two patients in the atezolizumab arm and one in the placebo-chemotherapy died of treatment-related causes.
 

 

 

Atezolizumab-chemo vs. placebo-chemo

Matthew D. Galsky, MD, of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, presented the second interim OS comparison of atezolizumab plus chemotherapy with placebo plus chemotherapy (Abstract CT042).

The primary analysis had shown a statistically significant improvement in PFS for patients on atezolizumab-chemotherapy, in comparison with placebo-chemotherapy, with encouraging OS improvement, but the boundary for declaring significance for the OS endpoint was not crossed (Lancet. 2020 May 16;395[10236]:1547-1557).

Because IMvigor130 included both patients who received cisplatin and patients who investigators deemed cisplatin ineligible, the second interim analysis included an exploratory analysis of whether there was a difference in outcome between patients who received or did not receive cisplatin.

At a median follow-up of 13.3 months, the median OS was not significantly different in the atezolizumab-chemotherapy arm (n = 451) and the placebo-chemotherapy arm (n = 400) – 16.1 months and 13.4 months, respectively (HR, 0.84; 95% CI, 0.71-1.00; P = .026).

There were no clinically or pathologically defined subgroups that experienced an OS benefit from atezolizumab-chemotherapy over placebo-chemotherapy.

As for subsequent nonprotocol therapy, 24% of the placebo-chemotherapy arm received an immune checkpoint inhibitor at progression, as did 7% of the atezolizumab-chemotherapy arm. There was no difference in receipt of an immune checkpoint inhibitor post progression among patients treated with cisplatin versus carboplatin.

The benefit of combining atezolizumab with chemotherapy appeared more substantial with cisplatin-based chemotherapy than with carboplatin-based treatment. With cisplatin, the median OS was 21.6 months for the atezolizumab-chemotherapy arm and 14.6 months for the placebo-chemotherapy arm. With carboplatin, the median OS was 14.3 months and 13.0 months, respectively.

PD-L1 status was prognostic for patients who received cisplatin, with lower OS being observed for patients with PD-L1 IC0/1 status and higher OS observed for patients with PD-L1 IC2/3 status. Atezolizumab plus cisplatin-based chemotherapy appeared superior to cisplatin-based chemotherapy alone in both PD-L1–low and –high groups.

Atezolizumab did not seem to benefit patients who were treated with carboplatin, and PD-L1 status did not seem to influence OS among the carboplatin-treated patients.

Although similar ORR results were seen with cisplatin and carboplatin, there appeared to be a longer median DOR among cisplatin-treated patients who received atezolizumab than among those who did not – 13.2 months and 8.3 months, respectively.

No such benefit from atezolizumab was seen in carboplatin-treated patients. The median DOR was 8.1 months among patients who received atezolizumab and 7.1 months among those who did not.

The overall safety profile for atezolizumab plus chemotherapy was consistent with prior reports of the combination. Treatment-related grade 3-5 adverse events were similar on the atezolizumab-chemotherapy arm and the placebo-chemotherapy arm.
 

The present and future

The investigators who presented the second interim analysis for OS of the IMvigor130 trial were appropriately modest in their conclusions. After all, the prespecified boundary for significant improvement in OS for the addition of atezolizumab to chemotherapy was not crossed. No change in guideline-based clinical practice would be appropriate at the present time.

The various exploratory analyses are hypothesis generating and invite potential mechanistic explanations. However, given the nonrandom allocation of patients to cisplatin- or carboplatin-based chemotherapy, unrecognized variables may have influenced any appearance of a difference in OS between the regimens.

In IMvigor130, treatment was given until unacceptable toxicity or disease progression. It is uncertain whether the current National Comprehensive Cancer Network category 1 recommendation of chemotherapy induction followed by immune checkpoint inhibitor maintenance therapy will prove superior to the IMvigor130 strategy.

Clearly – and concordant with current treatment guidelines – atezolizumab monotherapy can benefit some patients, though the response rate for atezolizumab monotherapy was lower than for chemotherapy (23.4% vs. 44.1%).

As noted by the session chair, Marina Chiara Garassino, MD, of the University of Chicago, the OS curves were initially superior for chemotherapy over atezolizumab. However, the apparent early OS benefit for chemotherapy dissipated over time and, among responders to atezolizumab, response duration was considerably longer than for chemotherapy.

IMvigor130 will ultimately have a final OS analysis to clarify the relative benefits of the various treatment strategies. Fortunately, this large phase 3 study will yield a treasure trove of data to inform future research and build on the advances of recent years for patients with advanced urothelial cancer.

IMvigor130 is sponsored by Hoffmann-La Roche. Dr. Davis, Dr. Galsky, and Dr. Garassino disclosed relationships with Hoffmann-La Roche and many other companies.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

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New data from the IMvigor130 trial have augmented oncologists’ knowledge about the treatment of locally advanced or metastatic urothelial carcinoma (mUC) with the immune checkpoint inhibitor atezolizumab.

Alan P. Lyss, MD
Dr. Alan P. Lyss

A second interim overall survival (OS) analysis suggested that atezolizumab monotherapy provides a clinical benefit as first-line treatment for mUC patients with PD-L1–expressing immune cells representing at least 5% of the tumor area (IC2/3), including patients who are cisplatin ineligible.

The analysis also suggested that atezolizumab plus chemotherapy produces similar OS results as chemotherapy plus placebo, but patients receiving atezolizumab may do better with cisplatin-based chemotherapy than with carboplatin-based chemotherapy.

These results were reported in two presentations at the American Association for Cancer Research Annual Meeting 2021: Week 1.

Current guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology recommend atezolizumab monotherapy for cisplatin-ineligible patients with mUC and PD-L1 IC2/3.

The ongoing phase 3 IMvigor130 trial was designed to compare atezolizumab plus gemcitabine/platinum chemotherapy, atezolizumab monotherapy, and placebo plus chemotherapy. Platinum-based chemotherapy included either cisplatin or carboplatin, per investigator choice.

Coprimary endpoints for IMvigor130 were progression-free survival (PFS) and OS for atezolizumab plus chemotherapy versus placebo plus chemotherapy. The hierarchical study design dictated that OS would only be assessed for the comparison of atezolizumab monotherapy versus placebo-chemotherapy in the overall and PD-L1 IC2/3 populations if there was statistical improvement in OS for the atezolizumab-chemotherapy arm over the placebo-chemotherapy arm.

Secondary endpoints were overall response rate (ORR; per RECIST 1.1), duration of response (DOR) for all patients, and PFS for the comparison between atezolizumab monotherapy and placebo-chemotherapy. Exploratory analyses were performed on cisplatin-ineligible patients by PD-L1 status.

At the time of the primary analysis, an OS benefit for atezolizumab-chemotherapy over placebo-chemotherapy was not observed. Therefore, the OS benefit of atezolizumab monotherapy versus placebo-chemotherapy was not assessed. However, a trend toward improved OS was noted with atezolizumab for PD-L1 IC2/3 patients, including cisplatin-ineligible patients.
 

Atezolizumab vs. placebo-chemo

Ian D. Davis, MBBS, PhD, of Monash University in Melbourne, presented the second interim analysis of OS with atezolizumab monotherapy versus placebo plus chemotherapy (Abstract CT040).

The median follow-up was 14.9 months for atezolizumab monotherapy (n = 360) and 11.8 months for placebo-chemotherapy (n = 359). The median OS was 15.2 months and 13.1 months, respectively (hazard ratio, 0.99; 95% confidence interval, 0.83-1.19). There was no apparent OS benefit of atezolizumab for any clinically selected subgroup.

The ORR was 23.4% for atezolizumab monotherapy and 44.1% for placebo-chemotherapy. The median DOR was more than 3.5 times longer for atezolizumab monotherapy than for placebo-chemotherapy – 29.6 months and 8.1 months, respectively.

Although there was no formal statistical comparison, exploratory subgroup analyses demonstrated that the median OS for the PD-L1 IC2/3 patients appeared higher in the atezolizumab monotherapy arm than in the placebo-chemotherapy arm – 27.5 months and 16.7 months, respectively.

Similarly, the median OS for cisplatin-ineligible PD-L1 IC2/3 patients appeared higher for atezolizumab monotherapy than for placebo-chemotherapy – 18.6 months and 10.0 months, respectively.

In terms of safety, atezolizumab monotherapy compared favorably with placebo plus chemotherapy. There were similar numbers of grade 3/4 adverse events and comparable adverse events leading to discontinuation of treatment in both arms.

The atezolizumab monotherapy arm had fewer adverse events leading to withdrawal from any treatment, when compared with the placebo-chemotherapy arm – 7% and 34%, respectively. Two patients in the atezolizumab arm and one in the placebo-chemotherapy died of treatment-related causes.
 

 

 

Atezolizumab-chemo vs. placebo-chemo

Matthew D. Galsky, MD, of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, presented the second interim OS comparison of atezolizumab plus chemotherapy with placebo plus chemotherapy (Abstract CT042).

The primary analysis had shown a statistically significant improvement in PFS for patients on atezolizumab-chemotherapy, in comparison with placebo-chemotherapy, with encouraging OS improvement, but the boundary for declaring significance for the OS endpoint was not crossed (Lancet. 2020 May 16;395[10236]:1547-1557).

Because IMvigor130 included both patients who received cisplatin and patients who investigators deemed cisplatin ineligible, the second interim analysis included an exploratory analysis of whether there was a difference in outcome between patients who received or did not receive cisplatin.

At a median follow-up of 13.3 months, the median OS was not significantly different in the atezolizumab-chemotherapy arm (n = 451) and the placebo-chemotherapy arm (n = 400) – 16.1 months and 13.4 months, respectively (HR, 0.84; 95% CI, 0.71-1.00; P = .026).

There were no clinically or pathologically defined subgroups that experienced an OS benefit from atezolizumab-chemotherapy over placebo-chemotherapy.

As for subsequent nonprotocol therapy, 24% of the placebo-chemotherapy arm received an immune checkpoint inhibitor at progression, as did 7% of the atezolizumab-chemotherapy arm. There was no difference in receipt of an immune checkpoint inhibitor post progression among patients treated with cisplatin versus carboplatin.

The benefit of combining atezolizumab with chemotherapy appeared more substantial with cisplatin-based chemotherapy than with carboplatin-based treatment. With cisplatin, the median OS was 21.6 months for the atezolizumab-chemotherapy arm and 14.6 months for the placebo-chemotherapy arm. With carboplatin, the median OS was 14.3 months and 13.0 months, respectively.

PD-L1 status was prognostic for patients who received cisplatin, with lower OS being observed for patients with PD-L1 IC0/1 status and higher OS observed for patients with PD-L1 IC2/3 status. Atezolizumab plus cisplatin-based chemotherapy appeared superior to cisplatin-based chemotherapy alone in both PD-L1–low and –high groups.

Atezolizumab did not seem to benefit patients who were treated with carboplatin, and PD-L1 status did not seem to influence OS among the carboplatin-treated patients.

Although similar ORR results were seen with cisplatin and carboplatin, there appeared to be a longer median DOR among cisplatin-treated patients who received atezolizumab than among those who did not – 13.2 months and 8.3 months, respectively.

No such benefit from atezolizumab was seen in carboplatin-treated patients. The median DOR was 8.1 months among patients who received atezolizumab and 7.1 months among those who did not.

The overall safety profile for atezolizumab plus chemotherapy was consistent with prior reports of the combination. Treatment-related grade 3-5 adverse events were similar on the atezolizumab-chemotherapy arm and the placebo-chemotherapy arm.
 

The present and future

The investigators who presented the second interim analysis for OS of the IMvigor130 trial were appropriately modest in their conclusions. After all, the prespecified boundary for significant improvement in OS for the addition of atezolizumab to chemotherapy was not crossed. No change in guideline-based clinical practice would be appropriate at the present time.

The various exploratory analyses are hypothesis generating and invite potential mechanistic explanations. However, given the nonrandom allocation of patients to cisplatin- or carboplatin-based chemotherapy, unrecognized variables may have influenced any appearance of a difference in OS between the regimens.

In IMvigor130, treatment was given until unacceptable toxicity or disease progression. It is uncertain whether the current National Comprehensive Cancer Network category 1 recommendation of chemotherapy induction followed by immune checkpoint inhibitor maintenance therapy will prove superior to the IMvigor130 strategy.

Clearly – and concordant with current treatment guidelines – atezolizumab monotherapy can benefit some patients, though the response rate for atezolizumab monotherapy was lower than for chemotherapy (23.4% vs. 44.1%).

As noted by the session chair, Marina Chiara Garassino, MD, of the University of Chicago, the OS curves were initially superior for chemotherapy over atezolizumab. However, the apparent early OS benefit for chemotherapy dissipated over time and, among responders to atezolizumab, response duration was considerably longer than for chemotherapy.

IMvigor130 will ultimately have a final OS analysis to clarify the relative benefits of the various treatment strategies. Fortunately, this large phase 3 study will yield a treasure trove of data to inform future research and build on the advances of recent years for patients with advanced urothelial cancer.

IMvigor130 is sponsored by Hoffmann-La Roche. Dr. Davis, Dr. Galsky, and Dr. Garassino disclosed relationships with Hoffmann-La Roche and many other companies.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

New data from the IMvigor130 trial have augmented oncologists’ knowledge about the treatment of locally advanced or metastatic urothelial carcinoma (mUC) with the immune checkpoint inhibitor atezolizumab.

Alan P. Lyss, MD
Dr. Alan P. Lyss

A second interim overall survival (OS) analysis suggested that atezolizumab monotherapy provides a clinical benefit as first-line treatment for mUC patients with PD-L1–expressing immune cells representing at least 5% of the tumor area (IC2/3), including patients who are cisplatin ineligible.

The analysis also suggested that atezolizumab plus chemotherapy produces similar OS results as chemotherapy plus placebo, but patients receiving atezolizumab may do better with cisplatin-based chemotherapy than with carboplatin-based chemotherapy.

These results were reported in two presentations at the American Association for Cancer Research Annual Meeting 2021: Week 1.

Current guidelines from the National Comprehensive Cancer Network and the European Society for Medical Oncology recommend atezolizumab monotherapy for cisplatin-ineligible patients with mUC and PD-L1 IC2/3.

The ongoing phase 3 IMvigor130 trial was designed to compare atezolizumab plus gemcitabine/platinum chemotherapy, atezolizumab monotherapy, and placebo plus chemotherapy. Platinum-based chemotherapy included either cisplatin or carboplatin, per investigator choice.

Coprimary endpoints for IMvigor130 were progression-free survival (PFS) and OS for atezolizumab plus chemotherapy versus placebo plus chemotherapy. The hierarchical study design dictated that OS would only be assessed for the comparison of atezolizumab monotherapy versus placebo-chemotherapy in the overall and PD-L1 IC2/3 populations if there was statistical improvement in OS for the atezolizumab-chemotherapy arm over the placebo-chemotherapy arm.

Secondary endpoints were overall response rate (ORR; per RECIST 1.1), duration of response (DOR) for all patients, and PFS for the comparison between atezolizumab monotherapy and placebo-chemotherapy. Exploratory analyses were performed on cisplatin-ineligible patients by PD-L1 status.

At the time of the primary analysis, an OS benefit for atezolizumab-chemotherapy over placebo-chemotherapy was not observed. Therefore, the OS benefit of atezolizumab monotherapy versus placebo-chemotherapy was not assessed. However, a trend toward improved OS was noted with atezolizumab for PD-L1 IC2/3 patients, including cisplatin-ineligible patients.
 

Atezolizumab vs. placebo-chemo

Ian D. Davis, MBBS, PhD, of Monash University in Melbourne, presented the second interim analysis of OS with atezolizumab monotherapy versus placebo plus chemotherapy (Abstract CT040).

The median follow-up was 14.9 months for atezolizumab monotherapy (n = 360) and 11.8 months for placebo-chemotherapy (n = 359). The median OS was 15.2 months and 13.1 months, respectively (hazard ratio, 0.99; 95% confidence interval, 0.83-1.19). There was no apparent OS benefit of atezolizumab for any clinically selected subgroup.

The ORR was 23.4% for atezolizumab monotherapy and 44.1% for placebo-chemotherapy. The median DOR was more than 3.5 times longer for atezolizumab monotherapy than for placebo-chemotherapy – 29.6 months and 8.1 months, respectively.

Although there was no formal statistical comparison, exploratory subgroup analyses demonstrated that the median OS for the PD-L1 IC2/3 patients appeared higher in the atezolizumab monotherapy arm than in the placebo-chemotherapy arm – 27.5 months and 16.7 months, respectively.

Similarly, the median OS for cisplatin-ineligible PD-L1 IC2/3 patients appeared higher for atezolizumab monotherapy than for placebo-chemotherapy – 18.6 months and 10.0 months, respectively.

In terms of safety, atezolizumab monotherapy compared favorably with placebo plus chemotherapy. There were similar numbers of grade 3/4 adverse events and comparable adverse events leading to discontinuation of treatment in both arms.

The atezolizumab monotherapy arm had fewer adverse events leading to withdrawal from any treatment, when compared with the placebo-chemotherapy arm – 7% and 34%, respectively. Two patients in the atezolizumab arm and one in the placebo-chemotherapy died of treatment-related causes.
 

 

 

Atezolizumab-chemo vs. placebo-chemo

Matthew D. Galsky, MD, of Mount Sinai Health System and Icahn School of Medicine at Mount Sinai in New York, presented the second interim OS comparison of atezolizumab plus chemotherapy with placebo plus chemotherapy (Abstract CT042).

The primary analysis had shown a statistically significant improvement in PFS for patients on atezolizumab-chemotherapy, in comparison with placebo-chemotherapy, with encouraging OS improvement, but the boundary for declaring significance for the OS endpoint was not crossed (Lancet. 2020 May 16;395[10236]:1547-1557).

Because IMvigor130 included both patients who received cisplatin and patients who investigators deemed cisplatin ineligible, the second interim analysis included an exploratory analysis of whether there was a difference in outcome between patients who received or did not receive cisplatin.

At a median follow-up of 13.3 months, the median OS was not significantly different in the atezolizumab-chemotherapy arm (n = 451) and the placebo-chemotherapy arm (n = 400) – 16.1 months and 13.4 months, respectively (HR, 0.84; 95% CI, 0.71-1.00; P = .026).

There were no clinically or pathologically defined subgroups that experienced an OS benefit from atezolizumab-chemotherapy over placebo-chemotherapy.

As for subsequent nonprotocol therapy, 24% of the placebo-chemotherapy arm received an immune checkpoint inhibitor at progression, as did 7% of the atezolizumab-chemotherapy arm. There was no difference in receipt of an immune checkpoint inhibitor post progression among patients treated with cisplatin versus carboplatin.

The benefit of combining atezolizumab with chemotherapy appeared more substantial with cisplatin-based chemotherapy than with carboplatin-based treatment. With cisplatin, the median OS was 21.6 months for the atezolizumab-chemotherapy arm and 14.6 months for the placebo-chemotherapy arm. With carboplatin, the median OS was 14.3 months and 13.0 months, respectively.

PD-L1 status was prognostic for patients who received cisplatin, with lower OS being observed for patients with PD-L1 IC0/1 status and higher OS observed for patients with PD-L1 IC2/3 status. Atezolizumab plus cisplatin-based chemotherapy appeared superior to cisplatin-based chemotherapy alone in both PD-L1–low and –high groups.

Atezolizumab did not seem to benefit patients who were treated with carboplatin, and PD-L1 status did not seem to influence OS among the carboplatin-treated patients.

Although similar ORR results were seen with cisplatin and carboplatin, there appeared to be a longer median DOR among cisplatin-treated patients who received atezolizumab than among those who did not – 13.2 months and 8.3 months, respectively.

No such benefit from atezolizumab was seen in carboplatin-treated patients. The median DOR was 8.1 months among patients who received atezolizumab and 7.1 months among those who did not.

The overall safety profile for atezolizumab plus chemotherapy was consistent with prior reports of the combination. Treatment-related grade 3-5 adverse events were similar on the atezolizumab-chemotherapy arm and the placebo-chemotherapy arm.
 

The present and future

The investigators who presented the second interim analysis for OS of the IMvigor130 trial were appropriately modest in their conclusions. After all, the prespecified boundary for significant improvement in OS for the addition of atezolizumab to chemotherapy was not crossed. No change in guideline-based clinical practice would be appropriate at the present time.

The various exploratory analyses are hypothesis generating and invite potential mechanistic explanations. However, given the nonrandom allocation of patients to cisplatin- or carboplatin-based chemotherapy, unrecognized variables may have influenced any appearance of a difference in OS between the regimens.

In IMvigor130, treatment was given until unacceptable toxicity or disease progression. It is uncertain whether the current National Comprehensive Cancer Network category 1 recommendation of chemotherapy induction followed by immune checkpoint inhibitor maintenance therapy will prove superior to the IMvigor130 strategy.

Clearly – and concordant with current treatment guidelines – atezolizumab monotherapy can benefit some patients, though the response rate for atezolizumab monotherapy was lower than for chemotherapy (23.4% vs. 44.1%).

As noted by the session chair, Marina Chiara Garassino, MD, of the University of Chicago, the OS curves were initially superior for chemotherapy over atezolizumab. However, the apparent early OS benefit for chemotherapy dissipated over time and, among responders to atezolizumab, response duration was considerably longer than for chemotherapy.

IMvigor130 will ultimately have a final OS analysis to clarify the relative benefits of the various treatment strategies. Fortunately, this large phase 3 study will yield a treasure trove of data to inform future research and build on the advances of recent years for patients with advanced urothelial cancer.

IMvigor130 is sponsored by Hoffmann-La Roche. Dr. Davis, Dr. Galsky, and Dr. Garassino disclosed relationships with Hoffmann-La Roche and many other companies.
 

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

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