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Relevant comparators
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| The submission was based on the IMpower010 study, which is a phase III randomized study comparing atezolizumab 1,200 mg IV every 3 weeks for 16 cycles (or 1 year) to BSC. | pERC noted that the comparison in the IMpower010 study was atezolizumab to BSC. |
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Considerations for initiation of therapy
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| Can pERC clarify the eligible patient population based on the AJCC, 8th edition, staging system? | pERC agreed with the clinical experts that the eligible population would include patients with fully resected tumours, who had a primary tumour > 5 cm regardless of nodal status or who’s disease was node positive, regardless of primary tumour size. While pERC acknowledged that the Health Canada indication for atezolizumab considered the 7th edition staging system, pERC recognized that the 8th edition staging system is currently used in Canadian clinical practice. pERC discussed the main differences between the 7th and 8th edition noted by the clinical experts that are relevant to the indication: In the 7th edition, T2 tumours were defined as measuring between > 3 cm and 7 cm. They were further subdivided into T2a > 3 cm to 5 cm and T2b > 5 cm to 7 cm. If a tumour was T2aN0 (node negative), it was stage IB. If a tumour was T2bN0, it was stage IIA. Adjuvant chemotherapy is offered to patients with node negative disease with tumours 4 cm or greater; thus, some patients with stage IB disease, per the 7th edition, qualified for adjuvant chemotherapy, while others did not. Likewise, some patients with stage IB disease, per the 7th edition, were eligible for enrolment in the IMpower010 study. In the 8th edition, a T2a tumour has been redefined to > 3 cm to 4 cm, T2b is now > 4 cm to 5 cm, and tumours > 5 cm to 7 cm are now T3. The overall staging for these groups has also shifted; in the 8th edition, T2aN0 remains stage IB, but T2bN0 is now stage IIA, and T3N0 is now stage IIB. The key difference is that those cancers included in the IMpower010 study, which used the 7th edition as stage IB with tumours that were between 4 cm and 5 cm and were node negative, would now be considered stage IIA under the 8th edition. These patients with IB per the 7th edition were not included in the analysis of patients with stage II and III from the IMpower010 study on which this submission is based; hence, in writing the indication using the current 8th edition, it would be a stage II or III node positive or node negative primary tumour > 5 cm. The data for patients with IB per the 7th edition from the IMpower010 study is still immature; however, it is possible that the indication for adjuvant atezolizumab would be extended to include those with tumours 4 cm to 5 cm with node negative disease. Patients with N2 nodal disease limited to a single nodal station are generally considered surgical candidates as long as there is no local invasion that would render a complete surgical resection unfeasible. In the 7th edition, patients with T2B (> 5 cm to 7 cm), N2, or T3N2 disease were considered stage IIIA, and would have been enrolled in the IMpower010 study if the tumours had been fully resected and the patient had received adjuvant chemotherapy. In the 8th edition, as was previously noted, those with primary tumours > 5 cm to 7 cm now have T3 disease, and those who are classified as T3N2 have been upstaged from stage IIIA to IIIB. Further, tumours that were T3 in the 7th edition on the basis of a primary tumour > 7 cm or invasion of the diaphragm are now classified as T4 in the 8th edition, and those who with T4N2 have been upstaged from stage IIIA to IIIB. Ultimately, this means that there are some patients with stage IIIB disease by the 8th edition who have tumours that are resectable, would have been considered stage IIIA in the 7th edition, and are thus eligible for enrolment in the IMpower010 study. These patients should not be excluded from receiving adjuvant atezolizumab because their staging in the 8th edition is stage IIIB, as long as their tumours were successfully resected and they were given appropriate adjuvant chemotherapy.
pERC agreed with the clinical experts that the eligible population based on the 8th edition would be patients with fully resected stage II to IIIA tumours who had a primary tumour > 5 cm regardless of nodal status or who’s cancer is node positive, regardless of primary tumour size. Patients with stage IIIB disease classified as stage T3N2 or T4N2 on the basis of a primary tumour > 7 cm or diaphragm involvement with fully resected tumours should also be eligible. |
| All patients in the IMpower010 study received prior cisplatin-based doublet chemotherapy. | pERC noted that the clinical experts highlighted that guidelines and mature trial evidence do not support the use of non-platinum containing doublet chemotherapy as adjuvant chemotherapy and that there were no non-cisplatin-based regimens studied in the IMpower010 study. |
| Patients in the IMpower010 study received a median 4 cycles (range of 1 to 4) of cisplatin-based chemotherapy. Is there a minimum number of cycles of chemotherapy required to be eligible for atezolizumab? | pERC agreed with the clinical experts that patients who become ineligible for cisplatin after 1 cycle due to toxicities should be eligible to receive atezolizumab. The clinical experts stated that given the propensity for adjuvant cisplatin-based chemotherapy to be toxic, and those toxicities being permanent and serious in some patients, any amount of chemotherapy would be acceptable. This is also reflective of the trial design. There is a group of patients who become ineligible for cisplatin after 1 cycle due to toxicities (examples include renal toxicity and ototoxicity). This group of patients should be eligible to receive atezolizumab. |
| Can pERC confirm that patients can be re-treated with downstream PD-1 or PD-L1 inhibitors provided that disease recurrence occurs more than 6 months from the last dose of adjuvant atezolizumab? | Yes and pERC acknowledged the clinical experts’ input. |
| Patients in the IMpower010 study were enrolled between 4 to 12 weeks after surgical resection and initiated chemotherapy thereafter. Within 3 to 8 weeks of completing chemotherapy, patients were randomized to atezolizumab. In clinical practice, when should chemotherapy be initiated after surgical resection? When should atezolizumab be initiated after chemotherapy? | pERC agreed with the clinical experts that chemotherapy should be initiated within 12 weeks of surgical resection. Starting atezolizumab within 3 to 8 weeks from the completion of chemotherapy is reasonable in the real world. |
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Considerations for prescribing of therapy
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| Would alternate dosing (i.e., 1,680 mg IV every 4 weeks) be reasonable to offer? | pERC agreed with the clinical experts that alternative dosing is reasonable. |
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Generalizability
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| Can the trial results be extended to patients with ECOG PS > 1? | pERC acknowledged the response from the clinical experts: Yes. The clinical experts explained that if a patient were robust enough to receive chemotherapy and had an ECOG PS of 2, they would be robust enough to receive atezolizumab. The clinical experts further described with an extrapolation from the metastatic setting that patients with an ECOG PS of 2 can benefit from immunotherapy. Finally, the clinical experts highlighted that they would not offer atezolizumab to patients if their ECOG PS was 3 to 4. |
| Should atezolizumab be offered to patients who had received platinum-chemotherapy when atezolizumab was not accessible, provided all other trial criteria are met (i.e., a time-limited need)? | pERC acknowledged the time-limited need at the initial onset of reimbursement of atezolizumab and agreed with the clinical experts. The clinical experts stated that chemotherapy should be initiated within 12 weeks of surgical resection. Starting atezolizumab within 3 to 8 weeks from the completion of chemotherapy is reasonable in the real world. According to the clinical experts, it may be reasonable to accept up to 12 weeks for patients who had received platinum-chemotherapy when atezolizumab was not accessible on a time-limited need; the clinical experts noted this would be infrequent and at the initial onset of reimbursement of atezolizumab. |
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Funding algorithm (oncology only)
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| Jurisdictions highlighted that NSCLC is a complex therapeutic space with multiple lines of therapy, subpopulations, or competing products. | pERC acknowledged the statement from the jurisdictions. |
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Care provision issues
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| PD-L1 testing would need to be in place to confirm patient eligibility. | pERC acknowledged that PD-L1 testing is required. |
